Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.50122025
They inhibit both COX 1 and COX 2 with up to 33 fold selectivity for COX 2 . . 0.50122025^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.5246482
In case of indoprofen specific changes between COX 1 and COX 2 were noted in helix D , H 6 , S 6 and helix H 8 in the cyclooxygenase cavity . 0.5246482^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The MRF 1 gene was cloned by genetic complementation of a respiratory deficient mutant disturbed in the expression of the mitochondrial genes encoding cytochrome c oxidase subunit 1 and 2 , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The organization of the mitochondrial genomes of the F 1 and succeeding backcross progenies was analyzed and compared with the progenitor RD WF 9 using probes derived from the S 1 and S 2 mitochondrial episomes , and probes containing the genes for cytochrome c oxidase subunit 1 ( coxI ) , cytochrome c oxidase subunit 2 ( coxII ) and apocytochrome b ( cob ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The sequence of the gene for cytochrome c oxidase subunit 1 , a frameshift containing gene for cytochrome c oxidase subunit 2 and seven unassigned reading frames in Trypanosoma brucei mitochrondrial maxi circle DNA . ^^^ A 9 . 2 kb segment of the maxi circle of Trypanosoma brucei mitochondrial DNA contains the genes for cytochrome c oxidase subunits 1 and 2 ( coxI and coxII ) and seven Unassigned Reading Frames ( `` URFs ' ' ) . ^^^ The reading frame coding for cytochrome c oxidase subunit 2 is discontinuous : the C terminal portion of about 40 aminoacids , is present in the DNA sequence in a 1 reading frame with respect to the N terminal moiety . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Alignment of the amino terminal amino acid sequence of human cytochrome c oxidase subunits 1 and 2 with the sequence of their putative mRNAs . ^^^ Thirteen of the first fifteen amino acids from the NH 2 terminus of the primary sequence of human cytochrome c oxidase subunit 1 and eleven of the first twelve amino acids of subunit 2 have been identified by microsequencing procedures . ^^^ This alignment has allowed the identification of the putative mRNA for subunit 1 , and has shown that the initiator codon for this subunit is only three nucleotides away from the 5 ' end of its mRNA ; furthermore , the results have substantiated the idea that the translation of human cytochrome c oxidase subunit 2 starts directly at the 5 ' end of its putative mRNA , as had been previously inferred on the basis of the sequence homology of human mitochondrial DNA with the primary sequences of the bovine subunit . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Complete sequences of cytochrome c oxidase subunit 2 ( COII ) , and ATPase subunit 8 ( ATPase 8 ) , as well as partial sequences of cytochrome c oxidase subunit 1 ( COI ) , NADH dehydrogenase subunit 6 ( ND 6 ) , and the large ribosomal RNA ( lrRNA ) genes were determined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These genes encode the proteins NADH dehydrogenase subunit 2 , cytochrome c oxidase subunit 1 , cytochrome c oxidase subunit 2 , and apocytochrome b , as well as the transfer RNAs tRNA ( Ile ) , tRNA ( Gln ) , tRNA ( Met ) , tRNA ( Ser ) ( UCN ) , tRNA ( Asp ) , tRNA ( Glu ) , tRNA ( Thr ) and tRNA ( Pro ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our study sequence included the 3 ' end of the cytochrome c oxidase subunit 1 ( CO 1 ) locus ( 183 to 198 total sites ; 91 informative sites ) , an intergenic spacer region of variable size ( 0 to 152 sites ) , the tRNA leucine locus ( 65 to 74 sites ) , and the 5 ' end of the cytochrome c oxidase subunit 2 ( co 2 ) locus ( 292 total sites ; 140 informative sites ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Sequence analysis confirmed that four of these clones contained DNA sequences from cytochrome c oxidase subunit 2 ( COX 2 ) , and one contained a DNA sequence from cytochrome c oxidase subunit 1 ( COX 1 ) . ^^^ Induction of c fos , and cytochrome c oxidase subunits 1 and 2 by gossypol acetic acid in rat liver cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Evolutionary rate acceleration of cytochrome c oxidase subunit 1 in simian primates . ^^^ We present an analysis of the evolutionary rates of the cytochrome c oxidase subunit 1 genes of primates and other mammals . ^^^ The species range and the overall magnitude of this rate increase are similar to those previously identified for the cytochrome c oxidase subunit 2 and cytochrome b genes . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vivo regulation of oxidative phosphorylation in cells harboring a stop codon mutation in mitochondrial DNA encoded cytochrome c oxidase subunit 1 . ^^^ To address this issue , cybrids were generated by fusing osteosarcoma cells devoid of mitochondrial DNA ( mtDNA ) with platelets from a patient with a stop codon mutation in cytochrome c oxidase subunit 1 ( COX 1 ) . ^^^ Cytochrome c oxidase subunit 2 was reduced proportionally to COX 1 , indicating impairment in complex assembly . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunohistochemical evidence of cytochrome C oxidase subunit 2 involvement in pulmonary hypertension syndrome ( PHS ) in broilers . ^^^ Thus , the major objective of this study was to determine whether differences in relative amounts of cytochrome c oxidase subunit 1 and 2 ( COX 1 and 2 ) can be detected by immunohistochemistry and digital image analysis in muscle tissue of broilers with PHS compared to control broilers . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Finally , we found increased mRNA expression of five unknown and five known genes , including cytochrome c oxidase subunit 1 ( COI ) , cyclooxygenase 2 ( COX 2 ) , matrix metalloproteinase 13 ( MMP 13 ) , Wiskott Aldrich syndrome protein interacting protein ( WASPIP ) , and hyaluronan synthase 2 ( HAS 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Thirty clones contained cDNAs corresponding to mitochondrial genes for ATP synthase subunit 6 ( ATP 6 ) , cytochrome c oxidase subunit 2 ( COXII ) , cytochrome c oxidase subunit 3 ( COXIII ) , NADH dehydrogenase subunit 1 ( ND 1 ) , NADH dehydrogenase subunit 4 ( ND 4 ) , and mitochondrial 12S rRNA . ^^^ Earlier we found the same for cytochrome c oxidase subunit 1 ( COXI ) Serial Analysis of Gene Expression ( SAGE ) showed lower content of the tags for all mitochondrial genes in GB SAGE libraries and together with our experimental data could serve as evidence of general inactivation of the mitochondrial genome in glioblastoma the most malignant and abundant form of human brain tumor . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Four structural genes ( for Cox 1 , Cox 2 , Atp 6 , and Atp 8 ) were located on the map by heterologous hybridizations with oligonucleote probes specific for yeast mitochondrial genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both Cox 1 and Cox 2 mRNAs are expressed in HUVEC , vascular smooth muscle cells , monocytes , and fibroblasts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of cyclooxygenase are known to be present in eukaryotic organisms : a cyclooxygenase ( COX 1 ) first purified from ram seminal vesicles encoded by a 2 . 8 kilobase mRNA , and a newly discovered mitogen inducible cyclooxygenase ( COX 2 ) encoded by a 4 kilobase mRNA . ^^^ Expression of these two forms of the enzyme in rat alveolar macrophages stimulated with lipopolysaccharide was investigated by 1 ) determining the activity of newly synthesized enzyme after inactivating the endogenous enzyme with aspirin ; 2 ) comparing levels of newly synthesized enzyme proteins in cells treated with or without lipopolysaccharide ; and 3 ) assessing the expression of the mRNAs encoding COX 1 and COX 2 . ^^^ Levels of enzyme proteins were assessed by Western blot analysis and immunoprecipitation of 35S labeled enzyme using two different antibodies , one specific for COX 2 and the other recognizing both forms of the enzyme but preferentially recognizing COX 1 . ^^^ Expression of COX 2 in macrophages stimulated by lipopolysaccharide was completely inhibited by dexamethasone , whereas COX 1 was unaffected . ^^^ In resting unstimulated macrophages , only COX 1 but not COX 2 was detected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using mt gene probes from Saccharomyces cerevisiae six structural genes ( cob , cox 1 , cox 2 , oli 1 , oli 2 , and 21S rRNA ) were located on the mitochondrial genome of A . adeninivorans . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Genes represented by these complementation groups are not required for mitochondrial transcription , transcript processing , or translation per se but are required for the expression of one of the three genes COX 1 , COX 2 , or COX 3 which encode the cytochrome c oxicase subunits 1 , 2 , or 3 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We therefore searched for GREs in the mitochondrial genome of human ( H ) , rat ( R ) and mouse ( M ) and found a number of such potential elements as follows : one within the 12s rRNA gene ( H 1 , R 1 and M 1 ) one within ( H 2 ) , or at the start ( R 2 , M 2 ) , of the presumptive protein 1 gene and three within the mouse cytochrome oxidase subunit 1 gene ( COX 1 , COX 2 and COX 3 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By hybridizing mitochondrial gene probes from Saccharomyces cerevisiae and Neurospora crassa with restriction fragments of Schizosaccharomyces pombe mitochondrial DNA , the following homologous genes were localized on the mitochondrial genome of S . pombe : cob , cox 1 , cox 2 and cox 3 , ATPase subunit 6 and 9 genes , the large rRNA gene and both types of open reading frames occurring in mitochondrial introns of various ascomycetes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Replacement of the methyl sulfone moiety with a sulfonamide group gave a slightly more potent ( typically 2 5 fold ) but less selective COX 2 inhibitor , mainly due to an increase ( 20 > 100 fold ) in COX 1 activity . ^^^ However , in vitro COX 1 / COX 2 selectivity for the sulfonamides 8 could be increased in many cases by simply incorporating a substituent at the 3 position of the phenyl group . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) plays a key regulatory role in prostaglandin synthesis , and occurs in both constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms . ^^^ COX 1 is thought to provide cytoprotective effects , whereas COX 2 is both inducible and the major isoform of inflammatory cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX exist : a constitutive ( COX 1 ) and an inducible ( COX 2 ) enzyme . ^^^ COX 1 and COX 2 proteins were assessed by Western blot . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A better understanding of anti inflammatory drugs based on isoforms of cyclooxygenase ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recombinant enzyme was characterized both by physical methods and activity measurements and shown to be fully active with kinetic properties similar to native COX 2 and COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
L 745 , 337 has IC 50 values of 23 + / 8 nM and > 10 microM for the inhibition of prostaglandin E 2 production in whole cell assays for COX 2 and COX 1 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A range of NSAIDs and reported Cox 2 selective compounds were tested in human freshly isolated platelets and LPS stimulated mononuclear cells to determine their potency and selectivity as inhibitors of constitutive ( presumably Cox 1 ) and inducible ( presumably Cox 2 ) cyclooxygenase respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IC 50 values for inhibition of purified COX 1 and COX 2 in vitro were slightly lower for lysine clonixinate ( 2 . 4 and 24 . 6 micrograms / ml , respectively ) than for ketorolac tromethamine ( 3 . 7 and 25 . 6 micrograms / ml , respectively ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently two forms of COX were identified a constitutively expressed COX 1 and a cytokine inducible COX 2 . ^^^ Commercially available NSAIDs like indomethacin inhibit both COX 1 and COX 2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non regulated or constitutive form of COX ( COX 1 ) in normal tissues , whereas therapeutic benefit derives from inhibition of the inducible enzyme , COX 2 , at the site of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 protein levels increased less than 2 fold and 8 fold , respectively , after IL 1 beta treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostacyclin formation by endothelial cells in atherosclerosis and diabetes is reviewed and the synthesis of prostacyclin by cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) is discussed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of COX are known : a constitutively expressed form ( COX 1 ) and a newly characterized , inducible form ( COX 2 ) . ^^^ In the present study , the immunocytochemical localization of COX 1 and COX 2 was examined in the rat gastrointestinal tract . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These experiments also illustrate selective induction of COX 2 mRNA without induction of COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs inhibit the enzymatic activity of both the constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms of COX enzyme . ^^^ We have investigated the expression of COX 1 and COX 2 polypeptides in human colon cancer tissues using immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nevertheless , COX 1 and COX 2 mRNAs and COX 2 protein were induced . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
T 614 inhibited the activity of purified COX 2 enzyme ( IC 50 : 7 . 7 micrograms / ml ) , but was inactive against both COX 1 activities of microsomal and purified enzymes ( IC 50 : > 300 micrograms / ml ) . ^^^ As a result , COX 1 mRNA was constitutively expressed in the cells , whereas COX 2 mRNA was not detected without stimulation with bradykinin , but was expressed within 30 min when stimulated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The constitutive cyclooxygenase 1 ( COX 1 ) can thus be considered a `` housekeeping ' ' enzyme , in contrast to cyclooxygenase 2 ( COX 2 ) which is activated by tissue damage . ^^^ Several non steroid anti inflammatory drugs which have more than 1 , 000 fold selectivity for COX 2 over COX 1 are in the early stages of drug development . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have evaluated the role of nitric oxide ( NO ) on the activity of the constitutive and induced forms of cyclooxygenase ( COX ; COX 1 and COX 2 , respectively ) . ^^^ Furthermore , sodium nitroprusside ( 0 . 25 1 mM ) increased arachidonic acid stimulated PGE 2 production by murine recombinant COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we investigated the effect of LPS , IFN gamma and TNF alpha in the regulation of cox 1 and cox 2 mRNA expression in PMA differentiated U 937 human macrophages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of the cyclo oxygenase enzyme ( COX 1 and COX 2 ) have been characterised . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PCR amplification of reverse transcribed mRNA from HPMC pre exposed to PDF pH 5 . 2 demonstrated suppression of IL 1 beta stimulated IL 6 and cyclooxygenase ( Cox 1 and Cox 2 ) transcripts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
ET 1 increased COX 2 , but not COX 1 , protein and mRNA levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , cyclooxygenase 1 ( COX 1 ) was shown constitutively expressed in mouse adherent and non adherent macrophages whereas expression of COX 2 was observed only in adherent cells , even when cultured in minimal conditions ( Ca , Mg and serum free medium ) . ^^^ These findings show that the macrophage can be used as a cellular model to study specifically COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX has been shown to exist in at least two distinct isoforms , designated COX 1 and COX 2 , and their gene expressions exhibit different profiles . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The numbers of cyclooxygenase ( COX ) enzyme positive cells were visualised by immunocytochemistry , using antibodies specific for COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently two forms of cyclo oxygenase have been described : a constitutive ( COX 1 ) enzyme present in most cells and tissues , and an inducible ( COX 2 ) isoenzyme observed in many cells in response to pro inflammatory cytokines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ten pairs of protein coding genes overlap by up to 38 bp and two subunits of cytochrome oxidase ( COX 1 and COX 2 ) are specified by a single continuous ORF . ( 2 ) Only three introns , all group 1 and each containing a free standing ORF , are present ; these are localized in the 3 ' half of the large subunit rRNA gene . ( 3 ) The genome encodes fewer than the minimal number of tRNA species required to support mitochondrial protein synthesis , suggesting that additional tRNAs are imported from the cytosol into A . castellanii mitochondria . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Differential measurement of constitutive ( COX 1 ) and inducible ( COX 2 ) cyclooxygenase expression in human umbilical vein endothelial cells using specific immunometric enzyme immunoassays . ^^^ The assay was specific for the cyclooxygenase 2 ( COX 2 ) isoform , since no immunoreactivity could be detected in platelet extracts known to be rich in cyclooxygenase 1 ( COX 1 ) . ^^^ The specificity of detection was further assessed by measuring the immunoreactivity of the fractions obtained after molecular sieve chromatography of control and stimulated cell extracts , and corroborated the marked enhancement of COX 2 by comparison with COX 1 . ^^^ Treatment of PMA activated cells with H 7 or actinomycin D totally abolished the COX 2 signal and had little effect on COX 1 . ^^^ These assays constitute the first quantitative analysis of constitutive COX 1 and of inducible COX 2 in nucleated cells at the protein level . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase 1 ( COX 1 ) is expressed constitutively whereas COX 2 is induced by lipopolysaccharide ( LPS ) and some cytokines in vitro and at the site of inflammation in vivo . ^^^ Epithelial cells may be an important source of prostaglandins in the airways and we have , therefore , investigated the expression of COX 1 or COX 2 isoforms in primary cultures of human airway epithelial cells or in a human pulmonary epithelial cell line ( A 549 ) . 2 . ^^^ COX 1 or COX 2 protein was measured by western blot analysis using specific antibodies to COX 2 and selective antibodies to COX 1 . ^^^ Thus , COX 1 or COX 2 activity was measured under two conditions ; initially the accumulation of the COX metabolites formed from endogenous arachidonic acid was measured after 24 h . ^^^ Untreated primary cells or A 549 cells contained low amounts of COX 1 or COX 2 protein . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms are recognized . ^^^ In this study , we correlated the steady state levels of COX 1 and COX 2 proteins with COX activity in resident AM and PM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms exist , being expressed constitutively ( Cox 1 ) , or inducibly in response to inflammatory mediators ( Cox 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In 1 mM GSH , the constitutive ( COX 1 ) and the mitogen inducible ( COX 2 ) isoforms metabolized arachidonate to 12 hydroxyheptadecatrienoic acid ( 12 HHT ) ( 88 % and 78 % of total products , respectively ) . ^^^ Prostanoid formation was consequently reduced to only 12 % ( COX 1 ) and 19 % ( COX 2 ) of the total metabolites . ^^^ Arachidonic acid oxidation by COX 1 , and not by COX 2 , was inhibited by the combined presence of GSH and liver cytosol . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) have been identified in eukaryotic cells : a constitutively expressed COX 1 and mitogen inducible COX 2 , which is selectively expressed in response to various inflammatory stimuli . ^^^ Thus , COX 2 instead of COX 1 is implicated to produce prostanoids mediating inflammatory responses . ^^^ Such NSAIDS would be more desirable anti inflammatory agents in comparison to NSAIDS which inhibit both COX 1 and COX 2 . ^^^ Other than glucocorticoids , pharmacological agents which can selectively suppress the expression of COX 2 without affecting that of COX 1 have not been identified . ^^^ We report here that radicicol , a fungal antibiotic , is a potent protein tyrosine kinase inhibitor , and that it inhibits the expression of COX 2 without affecting COX 1 expression in lipopolysaccharide ( LPS ) stimulated macrophages with the IC 50 value of 27 nM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis using isoform specific antibodies showed that the inducible cyclooxygenase enzyme , i . e . , COX 2 , was expressed by 2 h in IL 1 treated cells , while the constitutive COX 1 remained unaltered in its expression . ^^^ The close parallel between the kinetics of COX 2 mRNA and protein expression and PGE 2 accumulation in the medium , as well as the constitutive , unregulated nature of the COX 1 isoform , indicates that cytokine driven PGE 2 formation in WISH cells may be mediated by de novo expression of the novel COX 2 enzyme . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : COX 1 and COX 2 messenger RNA ( mRNA ) levels were determined by Northern blot analysis of poly ( A ) + RNA isolated from human colorectal cancers , adenomas , and accompanying normal mucosa . ^^^ CONCLUSIONS : COX 2 , but not COX 1 , gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
During induction of Cox 2 message and protein , expression of constitutive cyclooxygenase ( Cox 1 ) remains unchanged , however . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have utilized cDNA probes and antisera specific for the products of the prostaglandin synthase / cyclooxygenase 1 ( COX 1 ) and TIS10 / prostaglandin synthase 2 / cyclooxygenase 2 ( COX 2 ) genes to demonstrate that adrenalectomy causes elevation of mRNA and protein from the COX 2 gene , but not from the COX 1 gene , in peritoneal macrophages . ^^^ These data are consistent with COX 1 being the constitutive , housekeeping enzyme in macrophages in normal physiological conditions and with the enhanced prostaglandin synthesis seen after an inflammatory stimulus resulting from the rapid induction and activity of COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( Cox ) , a rate limiting enzyme in the synthesis of prostanoids , is encoded by two genes , Cox 1 and Cox 2 , which are differentially expressed and regulated . ^^^ The 3 ' UTRs of the Cox 1 and 2 genes are distinct ; for example , the largest exon in the Cox 2 gene encodes the entire 3 ' UTR , containing 22 copies of the ' AUUUA ' RNA instability element . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both inhibit the constitute ( COX 1 ) and inducible ( COX 2 ) isoforms of the enzyme with equal potency shortly after mixing , but their potencies increase with time for COX 2 selectively . ^^^ COX 2 that has been incubated with these inhibitors , and then extensively dialyzed against buffer , shows no recovery of enzyme activity , while complete recovery of activity is seen for COX 1 . ^^^ Thus , these inhibitors irreversibly inactivate COX 2 with time , while showing minimal reversible inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , a key enzyme in the formation of prostanoids , is known to exist in two isoforms : an inducible enzyme ( COX 2 ) and a constitutive from ( COX 1 ) . ^^^ Using other cell systems reported to express COX 1 or COX 2 , we obtained a similar selectivity for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two separate isoforms of cyclooxygenase ( COX ) have now been identified : constitutive COX 1 , encoded by a 2 . 8 kb mRNA , and mitogen activated COX 2 , encoded by a 4 . 0 4 . 5 kb mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of COX have been identified COX 1 , which is constitutively expressed in most tissues and organs , and the inducible enzyme , COX 2 , which has been localized primarily to inflammatory cells and tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exposure of HPMC to cytokines or PM S . epiCM resulted in the time dependent increase in the levels of both Cox 1 and Cox 2 mRNA as assessed by RT / PCR analysis with the greatest increase being seen for Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently two forms of the COX enzyme have been identified : COX 1 , which is constitutively expressed in many cells and tissues , and COX 2 , which is selectively induced by proinflammatory cytokines at the site of inflammation . ^^^ The discovery of a second COX enzyme led to the hypothesis that toxicity associated with the clinically useful NSAIDs is caused by the inhibition of COX 1 , whereas the anti inflammatory properties were caused by the inhibition of inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cyclooxygenase 1 ( COX 1 ) and COX 2 genes in myometria from preterm and term pregnancies was investigated by in situ hybridization , immunoblotting , and immunocytochemistry . ^^^ In situ hybridization revealed that myometrial smooth muscle contained both COX 1 and COX 2 messenger ribonucleic acid transcripts . ^^^ Immunoblotting revealed that myometria contained 55 and 67 kilodalton COX 1 proteins as well as 72 and 56 kilodalton COX 2 proteins . ^^^ Immunocytochemistry showed that COX 1 and COX 2 proteins are present in the myometrial smooth muscle . ^^^ The expression of COX 1 and COX 2 genes differed in myometria . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Active cyclooxygenase is encoded by two distinct and independently regulated genes , termed cyclooxygenase 1 ( cox 1 ) and cyclooxygenase 2 ( cox 2 ) . ^^^ In this investigation , we examined the expression of cox 1 and cox 2 mRNA in rat aorta following balloon deendothelialization ( BDE ) in vivo and in rat aortic smooth muscle cells ( SMC ) after serum stimulation in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Under basal conditions both Cox 1 and 2 mRNAs were present at low levels , but Cox 2 mRNA was markedly increased by treatment with IL 1 beta or PMA . dex markedly suppressed the induction of Cox 2 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , two forms of cyclooxygenase have been identified : a COX 1 first purified from ram seminal vesicles and a newly discovered mitogen inducible form ( COX 2 ) . ^^^ COX 1 purified from ram seminal vesicles and COX 2 isolated from sheep placenta ( purity was 70 % ) were used . ^^^ The COX 1 activity was completely unaffected by 10 ( 4 ) M NS 398 , whereas the COX 2 activity was concentration dependently inhibited , the IC 50 value being 3 . 8 10 10 ( 6 ) M . ^^^ Indomethacin inhibited both COX 1 and COX 2 activity to the same degree , the IC 50 values being 7 . 4 10 10 ( 7 ) M and 9 . 7 10 10 ( 7 ) M , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase , a key enzyme in prostaglandin production , is mainly in the constitutive form ( COX 1 ) in gastric mucosa , whereas leucocytes have an inducible enzyme ( COX 2 ) . ^^^ The finding that acemetacin is equipotent to indomethacin on leucocyte cyclo oxygenase ( inducible enzyme , COX 2 ) but less active on the gastric mucosa ( COX 1 ) is consistent with an effective analgesic and anti inflammatory activity of acemetacin coupled with better gastric tolerance than that to indomethacin . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present studies investigated the expression of TXA 2 synthase gene along with those of TXA 2 receptors , PGI 2 synthase , cyclooxygenase 1 ( COX 1 ) , and COX 2 in placental and decidual tissue from preeclamptic and normal pregnancies . ^^^ In situ hybridization and immunocytochemistry showed that primarily trophoblast layer and decidual cells express TXA 2 synthase , COX 1 , and COX 2 enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase activity of HUVEC challenged with interleukin 1 alpha or a phorbol ester increased in parallel with the mass of a protein doublet analyzed by Western blot using antibodies directed against the Cox 2 peptide ; a monoclonal antibody directed against Cox 1 showed a small change in protein mass . ^^^ Both immunoprecipitated Cox 1 and Cox 2 possessed cyclooxygenase activity that was inhibited by flurbiprofen . ^^^ Endoglycosidase H treatment of immunoprecipitated Cox 2 proteins caused a decline in the apparent molecular size similar to that observed with immunoprecipitated Cox 1 or sheep cyclooxygenase but did not suppress the doublet . ^^^ These results show by direct protein measurement that HUVEC synthesize the novel Cox 2 under appropriate stimulation , with little changes of Cox 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indeed , cholesterol enrichment attenuated IL 1 beta , PDGF , and TNF alpha induced PGI 2 synthesis relative to controls and was consistent with the results of in vitro labeling experiments demonstrating that cholesterol enrichment reduced the incorporation of [ 35S ] methionine into immunoprecipitable COX 1 and COX 2 following induction by PDGF . ^^^ Taken together , these data demonstrate that reduced eicosanoid synthesis in smooth muscle derived foam cells is due , in part , to impaired transcription of mRNA for COX 1 and COX 2 as well as fatty acid remodeling in membrane phospholipids . ^^^ These findings support the hypothesis that cholesterol enrichment alters posttranscriptional processing of COX 1 expression , as well as altering COX 2 gene expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive cyclooxygenase ( COX 1 ; prostaglandin endoperoxide synthase , EC 1 . 14 . 99 . 1 ) is present in cells under physiological conditions , whereas COX 2 is induced by some cytokines , mitogens , and endotoxin presumably in pathological conditions , such as inflammation . ^^^ Therefore , we have assessed the relative inhibitory effects of some nonsteroidal antiinflammatory drugs on the activities of COX 1 ( in bovine aortic endothelial cells ) and COX 2 ( in endotoxin activated J774 . 2 macrophages ) in intact cells , broken cells , and purified enzyme preparations ( COX 1 in sheep seminal vesicles ; COX 2 in sheep placenta ) . ^^^ Aspirin , indomethacin , and ibuprofen were more potent inhibitors of COX 1 than COX 2 in all models used . ^^^ Diclofenac , BW 755C , acetaminophen , and naproxen were approximately equipotent inhibitors of COX 1 and COX 2 in intact cells . ^^^ The use of such models of COX 1 and COX 2 activity will lead to the identification of selective inhibitors of COX 2 with presumably less side effects than present therapies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) have been identified in eukaryotic cells : COX 1 encoded by a 2 . 8 kb mRNA , and a mitogen inducible COX 2 encoded by a 4 kb mRNA . ^^^ We have cloned the COX 1 and COX 2 cDNAs from the cDNA library constructed from lipopolysaccharide ( LPS ) stimulated rat peritoneal macrophages . ^^^ The deduced amino acid sequence showed that COX 1 contained 602 amino acids , whereas COX 2 contained 604 amino acids . ^^^ In rat vascular smooth muscle cells , interleukin 1 beta selectively increased the expression of COX 2 , but not that of COX 1 , as assessed by enzyme activity , immunoprecipitation of COX proteins , and mRNA analysis . ^^^ However , COX 2 mRNA was expressed in vivo in the lung and kidney , but not in the heart , after systemic administration of LPS , suggesting that COX 2 but not COX 1 plays a major role in producing COX derived products of arachidonic acid during endotoxic shock . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Experiments were conducted to determine the roles of the rate limiting enzymes , cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) and cytoplasmic phospholipase A 2 ( PLA 2 ) , in transforming growth factor beta ( TGF beta ) and interleukin 1 ( IL 1 beta ) activated prostaglandin synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cox has been found to exist as two distinct genes , Cox 1 and Cox 2 . ^^^ Quantitation of PCR efficiency indicated an approximate 100 fold excess of Cox 2 messenger RNA over that for Cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of cyclooxygenase have been characterized : a ubiquitously expressed form ( COX 1 ) and a recently described second form ( COX 2 ) inducible by various factors including mitogens , hormones , serum and cytokines . ^^^ Here we quantitate by the reverse transcriptase polymerase chain reaction ( RT PCR ) the expression of COX 1 and COX 2 mRNA in human tissues including lung , uterus , testis , brain , pancreas , kidney , liver , thymus , prostate , mammary gland , stomach and small intestine . ^^^ All tissues examined contained both COX 1 and COX 2 mRNA and could be grouped according to the level of COX mRNA expression . ^^^ The highest levels of COX mRNAs were detected in the prostate where approximately equal levels of COX 1 and COX 2 transcripts were present . ^^^ In the lung high levels of COX 2 were observed whereas COX 1 mRNA levels were about 2 fold lower . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mutations were mapped to the three catalytic subunits encoding genes ( COX 1 , COX 2 and COX 3 ) of the cytochrome c oxidase ( 70 mutations ) and to the cytochrome b gene ( 15 mutations ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases 1 and 2 ( COX 1 and COX 2 ) are key enzymes in prostaglandin biosynthesis and the target enzymes for the widely used nonsteroidal anti inflammatory drugs . ^^^ COX 1 deficient mice provide a useful model to distinguish the physiological roles of COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition to a constitutive cyclo oxygenase ( Cox 1 ) , human endothelial cells also possess an inducible cyclo oxygenase ( Cox 2 ) which plays an important role in the regulation of the synthesis of prostacyclin ( prostaglandin I 2 ) . ^^^ This stimulation was accompanied by the induction of Cox 2 protein , detectable after stimulation for 1 h , which is consistent with an increase in activity reflected by prostacyclin synthesis ; no variation in the expression of Cox 1 could be observed . ^^^ Under these conditions , there was selective reduction of Cox 2 expression without modification of Cox 1 . ^^^ Our results suggest that within the time frame of our experiments these effects on kinases are specific for Cox 2 rather than Cox 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When Northern blots of IL 1 beta treated and control cells were probed with cDNAs encoding either COX 1 or COX 2 isoforms or an oligonucleotide probe encoding a portion of the human beta actin , we detected a time and dose dependent increase in the steady state levels of COX 2 , but not COX 1 or beta actin mRNA transcripts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Studies were undertaken to compare meloxicam to other NSAIDS in their ability to inhibit either constitutive cyclooxygenase ( COX 1 ) or inducible cyclooxygenase ( COX 2 ) . ^^^ In cell free enzyme preparations , however , meloxicam showed the same activity against COX 1 and COX 2 . ^^^ All other NSAIDs tested were more potent inhibitors of COX 1 than of COX 2 . ^^^ The inducible cyclooxygenase COX 2 has been implicated in the mediation of the inflammatory reaction , whereas the products of the constitutive cyclooxygenase COX 1 have cytoprotective effects in the gastric mucosa , support microcirculation in the kidney , and are antithrombogenic . ^^^ Therefore , differential inhibitory effects of NSAIDs on COX 1 and COX 2 may have a bearing on the risk benefit profile displayed in clinical practice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This report summarizes studies undertaken to compare meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase ( COX 2 ) in inflamed areas ( pleurisy of the rat , peritonitis of mice ) and their influence on the activity of the constitutive cyclooxygenase ( COX 1 ) in stomach , kidney , brain , and blood . ^^^ The in vivo findings confirm the results of in vitro tests , conducted separately , showing that meloxicam preferentially inhibits COX 2 over COX 1 . ^^^ COX 2 is the inducible isoenzyme implicated in the inflammatory response , whereas COX 1 has cytoprotective effects in the gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To examine the effects of IL 13 on PG synthesis , we measured the mRNA levels of cytosolic phospholipase A 2 ( cPLA 2 ) , constitutively expressed cyclooxygenase ( COX 1 ) and inducible COX ( COX 2 ) in mouse osteoblast like cells . ^^^ IL 1 alpha markedly stimulated the mRNA expression of COX 2 , but not that of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TNF alpha increased the amounts of mRNA for COX 2 but not for COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Of the two isoforms of cyclooxygenase ( COX 1 and COX 2 ) , COX 1 activity was inhibited by oxime 2 and 4 ' piperidinoacetophenone oxime ( oxime 3 ) with IC 50 values of 50 and 130 microM , respectively , while COX 2 activity was not inhibited . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The gastric mucosa synthesizes prostaglandins mainly via constitutive cyclooxygenase ( COX 1 ) , whereas leucocytes have inducible enzyme ( COX 2 ) . ^^^ In vitro assays with COX 1 from ram seminal vesicles , or COX 2 from sheep placenta , were performed by pre incubating the enzymes with vehicle alone ( controls ) or with drug for 5 min at 37 degrees C . ^^^ With the in vitro assay , nimesulide ( 0 . 01 to 100 mumol / l ) did not inhibit PGE formation by COX 1 but caused a concentration related inhibition of PGE formation by COX 2 ( 4 60 % ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently two forms of cyclooxygenase have been isolated , one ( COX 1 ) being `` constitutive ' ' , the other ( COX 2 ) being mitogen inducible . ^^^ Nimesulide ( CAS 51803 78 2 ) has been shown to inhibit with high selectivity COX 2 without affecting COX 1 activity , so explaining the previous observations about the selectivity of the anti prostaglandin effect of the drug . ^^^ So we evaluated the time dependency of the effect of nimesulide on COX 1 and COX 2 . ^^^ COX 1 was isolated from ram seminal vesicles , and COX 2 was from sheep placenta . ^^^ In conclusion nimesulide ' s selective inhibitory effect on COX 2 is time dependent whereas its weak effect on COX 1 is not time dependent . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of cyclooxygenase , cox 1 and cox 2 , appear to be differentially inhibited by NSAIDs . ^^^ Because cox 1 is responsible for maintaining normal physiologic function in gastric mucosa and other tissue , `` ideal ' ' NSAIDs would suppress only cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Epidermal expression of the two isoforms of the prostaglandin H generating cyclooxygenase ( COX 1 and COX 2 ) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes . ^^^ In normal human skin , COX 1 immunostaining is observed throughout the epidermis whereas COX 2 immunostaining increases in the more differentiated , suprabasilar keratinocytes . ^^^ Basal cell carcinomas express little if any COX 1 or COX 2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis . ^^^ In human keratinocyte cultures , raising the extracellular calcium concentration , a recognized stimulus for keratinocyte differentiation , leads to an increased expression of both COX 2 protein and mRNA ; expression of COX 1 protein , however , shows no significant alteration in response to calcium . ^^^ Because of a recent report that failed to show COX 2 in normal mouse epidermis , we also looked for COX 1 and COX 2 immunostaining in sections of normal and acetone treated mouse skin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One target for NSAIDs is cyclooxygenase ( COX ) , and two isoforms of this enzyme have been identified : COX 1 and COX 2 . ^^^ METHODS : COX 1 and COX 2 messenger RNA levels were determined by Northern blot analysis of total RNA isolated from colonic tumors and normal adjacent mucosa . ^^^ CONCLUSIONS : COX 2 but not COX 1 gene expression is markedly elevated in most colonic tumors examined in azoxymethane treated rodents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inducible cyclooxygenase 2 ( COX 2 ) , but not constitutive COX 1 , can be upregulated in rheumatoid synovial tissue by interleukin 1 beta and phorbol esters and is inhibited by dexamethasone . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This improved safety profile is likely to be due to meloxicam ' s selective inhibition of COX 2 relative to COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It exists in two isoforms , constitutive COX 1 ( responsible for physiological functions ) and inducible COX 2 ( involved in inflammation ) . ^^^ Inhibition of COX explains both the therapeutic effects ( inhibition of COX 2 ) and side effects ( inhibition of COX 1 ) of non steroidal anti inflammatory drugs ( NSAIDs ) . ^^^ Adverse event data of marketed NSAIDs show a relationship between a poor safety profile and more potent inhibition of COX 1 relative to COX 2 . ^^^ The most clinically advanced is meloxicam , which consistently demonstrates higher activity against COX 2 than COX 1 in several test systems . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new non steroidal anti inflammatory drug ( NSAID ) , which has a higher activity against cyclooxygenase 2 ( COX 2 ) than against cyclooxygenase 1 ( COX 1 ) , with potentially high anti inflammatory and analgesic action . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new non steroidal anti inflammatory drug ( NSAID ) which preferentially inhibits cyclooxygenase 2 ( COX 2 ) over cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam ' s improved GI safety profile is likely to be due to its preferential inhibition of inducible COX 2 relative to constitutive COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have investigated the expression of a continuous open reading frame ( ORF ) present in the mitochondrial genome of Acanthamoeba castellanii and specifying the two largest subunits ( COX 1 and COX 2 ) of the cytochrome c oxidase complex . ^^^ Between the cox 1 and cox 2 portions of the transcript , RNA sequence exactly matches gene sequence , excluding the possibility that a standard cox 1 termination codon is created by post transcriptional RNA processing or editing . ^^^ These observations indicate that although A . castellanii COX 1 and COX 2 are apparently translated from the same ORF , they do not exist in mature form as a COX 1 COX2 `` fusion ' ' protein . ^^^ Whereas translation of COX 2 could potentially be initiated from an internal AUG codon in the cox1 / 2 ORF , COX 1 must be generated either through an unusual translation termination mechanism acting between the cox 1 and cox 2 coding regions of the cox1 / 2 mRNA , or by co translational or post translational proteolytic processing of a translation product whose synthesis continues into the cox 2 coding region . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The identified genes that are typical for most fungal mitochondria include those for the large ( rnl ) and small subunit ( rns ) ribosomal RNAs , a complete set of 25 tRNAs , three ATPase subunits ( atp 6 , atp 8 and atp 9 ) , apocytochrome b ( cob ) , three subunits of the cytochrome oxidase complex ( cox 1 , cox 2 and cox 3 ) , and seven subunits of the NADH dehydrogenase complex ( nad 1 , nad 2 , nad 3 , nad 4 , nad4L , nad 5 and nad 6 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We refer to these isoforms as cyclooxygenase 1 ( COX 1 ) and COX 2 in this review . ^^^ Interestingly , disruption of the COX 1 gene results in distinct phenotypic changes different from those observed for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although two isoforms of COX ( COX 1 and COX 2 ) have been identified in the ovary , the nature and physiological significance of their regulation by transforming growth factor ( TGF ) alpha and TGF beta are unclear . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent studies , including the generation of knockout mice , show COX 1 and COX 2 to have biologically distinct roles within cells and organisms . ^^^ Because COX 1 and COX 2 are highly conserved in all residues needed for catalysis and in their purified forms have almost identical kinetic properties , we have searched for COX interacting ER proteins that might mediate these unique isoenzymic properties . ^^^ COX Nuc binding was substantiated by immunoprecipitation experiments , which showed that COX 1 and , to a lesser extent , COX 2 form complexes with Nuc in vitro . ^^^ However , when Nuc was co overexpressed with COX 1 or COX 2 , its release was reduced by > 80 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive cyclooxygenase ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) : rationale for selective inhibition and progress to date . ^^^ The widespread distribution of both COX 1 and COX 2 coupled with the capacity of most vascular beds , smooth muscle , as well as leukocytes to respond to prostanoids make drawing generalities difficult . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Enzyme activity of the newly synthesized Cox 2 in aspirin treated cells , evaluated after immunoprecipitation , was similar to untreated cells but after 18 h of cell stimulation only 50 60 % recovery of Cox 1 was observed . ^^^ Cyclooxygenase activity was related to the amount of Cox proteins present in the cells , but after induction of Cox 2 , contribution of the latter to PG production was 6 8 fold that of Cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A single amino acid difference between cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) reverses the selectivity of COX 2 specific inhibitors . ^^^ Nonsteroidal anti inflammatory drugs ( NSAIDs ) currently available for clinical use inhibit both COX 1 and COX 2 . ^^^ This suggests that clinically useful NSAIDs inhibit pro inflammatory prostaglandins ( PGs ) derived from the activity of COX 2 , as well as PGs in tissues like the stomach and kidney ( via COX 1 ) . ^^^ A new class of compounds has recently been developed ( SC 58125 ) that have a high degree of selectivity for the inducible form of cyxlooxygenase ( COX 2 ) over the constitutive form ( COX 1 ) . ^^^ This unique class of compounds exhibit a time dependent irreversible inhibition of COX 2 , while reversibly inhibiting COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is hypothesised ( De Witt et al . , 1993 ) that the analgesic / anti inflammatory effect of current NSAIDs is achieved through inhibition of COX 2 , whereas their side effects ( such as antral ulceration ) result as a consequence of inhibition of gastric COX 1 . ^^^ If key mechanisms ( such as alterations in blood flow ) of NSAID induced antral damage can be identified , then it would be hypothesised that selective inhibitors of COX 1 would be ulcerogenic and reduce antral blood flow , whereas inhibitors of COX 2 would not share either of these properties . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To characterise the effect of interleukin 4 ( IL 4 ) on the biosynthesis of cyclo oxygenases 1 ( COX 1 ) and 2 ( COX 2 ) , the rate limiting enzymes of the synthesis of prostaglandin E 2 ( PGE 2 ) , in freshly prepared rheumatoid synovial cells . ^^^ The protein and mRNA concentrations of COX 1 and COX 2 were determined by Western blotting and reverse transcription polymerase chain reaction , respectively . ^^^ They also showed increased gene expression of COX 1 and COX 2 , and synthesised these proteins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Enzymes essential for PG biosynthesis , cyclooxygenase isozymes COX 1 and COX 2 , have not yet been investigated in the spinal cord . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme are known to exist in the brain ; one of these ( type 1 COX or COX 1 ) is constitutively expressed , whereas the other form of the enzyme , which is inducible , has been called type 2 COX ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , heterologous expression of the hybrid Cox 1 open reading frame and the Cox 2 3 ' UTR results in the accumulation of high levels of the short isoform and lower levels of the long isoform . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX , prostaglandin G / H synthase ) is a key enzyme in prostaglandin synthesis and has two isoforms ( COX 1 and COX 2 ) . ^^^ COX 1 is constitutively expressed and is probably responsible for prostaglandin release under physiological conditions , whereas COX 2 is expressed at high levels upon induction . 2 . ^^^ We investigated the effect of lipopolysaccharide treatment in vivo on differential COX 1 and COX 2 mRNA expression in the rat . 3 . ^^^ Neither the down regulation of COX 1 nor the upregulation of COX 2 mRNA induced by lipopolysaccharide was significantly affected by pretreatment with dexamethasone in lung and heart , although expression of inducible nitric oxide synthase , induced by lipopolysaccharide , was markedly inhibited in the same tissues . 4 . ^^^ The down regulation of COX 1 and upregulation of COX 2 may contribute to the multi organ failure seen in sepsis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we evaluated the effect of several NSAIDs on COX 1 and COX 2 mRNA , protein expression and PGE 2 production in PMA differentiated THP 1 and U 937 human macrophages stimulated with LPS . ^^^ Macrophages pre treated with acetylsalicylic acid , indomethacin , naproxen or NS 398 and stimulated with LPS showed a marked inhibition on PGE 2 production but not on COX 1 or COX 2 mRNA and protein expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , a second isoform of COX ( COX 2 ) was discovered , which differed from COX 1 with respect to protein structure , transcriptional regulation , and susceptibility to inhibition by pharmacological agents . ^^^ It is now known that indomethacin nonselectively inhibits COX 1 and COX 2 , whereas NS 398 is a selective inhibitor of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Excretion is depressed by antioxidant vitamins , although not by the nonspecific cyclooxygenase ( COX ) inhibitor , aspirin , even though 8 epi PGF 2 alpha may be formed by either COX 1 or COX 2 . 3 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is concluded that the chiral NSAIDs studied here inhibit with comparable stereoselectivity both COX 2 and COX 1 isoenzymes , and that the inhibition of COX 2 previously observed for racemic NSAIDs should be attributed almost exclusively to their S enantiomers . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we have examined the inhibitory potency of selected compounds for the enzymes human COX 1 , human COX 2 , human MP , and rat liver 3 alpha HSD . ^^^ The compounds selected span a range of COX isoform selectivities , from specific for COX 2 to selective for COX 1 only , and include three representative tri cyclic aromatics . ^^^ Examples of COX 1 selective , and COX 2 selective inhibitors within this structural class are presented . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One of the mechanisms by which nonsteroidal antiinflammatory agents inhibit colon carcinogenesis is through the inhibition of prostaglandin production by cyclooxygenase isozymes ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biosynthesis of prostaglandins from arachidonic acid is regulated by the enzyme cyclooxygenase which exists in two forms ; the constitutive form ( COX 1 ) and the other mitogen inducible ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Second , cis fatty acid induced lipid body formation was not impaired in macrophages from COX 1 or COX 2 genetically deficient mice . ^^^ Finally , NSAIDs inhibited arachidonic acid induced lipid body formation likewise in macrophages from wild type and COX 1 and COX 2 deficient mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : Prostaglandin synthase ( cyclooxygenase ) is now known to exist in two separate isoforms , termed prostaglandin synthase 1 and 2 ( or COX 1 and COX 2 ) . ^^^ The emerging picture is that COX 1 is responsible for maintaining prostaglandin synthesis in the gastric mucosa , platelets , and kidney , whereas COX 2 is responsible for prostaglandin production in inflamed tissues , including rheumatoid arthritis ( RA ) synovium . ^^^ This review examines the validity of the hypothesis that NSAIDs exhibiting selectivity for COX 2 demonstrate an improved safety and efficacy profile when compared with NSAIDs exhibiting selectivity for COX 1 . ^^^ METHODS : Literature on the efficacy and safety ( gastric , renal , and hemostatic ) of various NSAIDs are compared with published data on their relative COX 1 and COX 2 in vitro specificity . ^^^ RESULTS : No differences in clinical efficacy are evident between NSAIDs exhibiting preferential activity for either COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The role of cyclooxygenase 2 ( COX 2 ) versus COX 1 inhibiting agents was also examined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL 4 , TGF beta 1 , and DXS abolished PGE 2 production and the expression of COX 2 and cPLA 2 but failed to affect the constitutive expression of COX 1 and secreted PLA 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The synthesis of prostaglandins in the uterus at term are modulated by two isoforms of the enzyme cyclooxygenase ( COX ) : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It has greater in vitro and in vivo inhibitory action against the inducible isoform of cyclo oxygenase ( COX 2 ) , which is implicated in the inflammatory response , than against the constitutive form of this enzyme ( COX 1 ) , inhibition of which is associated with gastric , renal and other adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When tested on human and murine recombinant COX 1 and COX 2 enzymes , DuP 697 was at least 50 fold more selective for COX 2 than for COX 1 . 3 . ^^^ Indomethacin ( 1 microM ) , a non selective COX 1 and COX 2 inhibitor , completely inhibited PGE 2 release in the normal contralateral as well as in the hydronephrotic kidney . 6 . ^^^ We suggest that renal prostaglandin production in the normal kidney is driven by the activity of constitutive COX 1 while at sites of inflammation , such as the hydronephrotic kidney , there is induction of COX 2 that can be blocked selectively by anti inflammatory glucocorticoids or selective COX 2 inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of the present study was to investigate the involvement of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in PGE 2 production by human gingival fibroblasts stimulated with lipopolysaccharides ( LPS ) from periodondopathogenic bacteria . ^^^ Treatment of the cells with indomethacin , a non selective COX 1 / COX 2 inhibitor and NS 398 , a selective COX 2 inhibitor , completely depressed PGE 2 production . ^^^ Immunohistochemical staining of COX 2 protein demonstrated that expression of COX 2 protein was increased at 24 h after P gingivalis LPS stimulation , while expression of COX 1 protein was not affected by P . gingivalis LPS . ^^^ These data suggest that human gingival fibroblasts stimulated with LPS from periodontopathogenic bacteria mainly produce PGE 2 not by COX 1 , but by COX 2 , induction of which may be regulated by tyrosine kinase and that the produced PGE 2 may be involved in the pathogenesis of periodontal diseases . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The sequence of the 3 ' UTR of the Cox 1 transcripts is highly divergent from that of the human Cox 2 transcript isoforms , suggesting a distinct function in the regulation of expression at the post transcriptional and / or translational levels . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Distinct isoforms ( COX 1 and COX 2 ) of cyclooxygenase : possible physiological and therapeutic implications . ^^^ Indeed , new pharmacological results suggest that COX 2 inhibition provides the therapeutic ( ie , anti inflammatory ) activity of NSAIDs , whereas inhibition of constitutive COX 1 is responsible for their gastric and renal side effects as well as for their antithrombotic activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In two different in vitro human test systems , tenidap inhibited COX 1 activity more potently than COX 2 , although the relative potency ratio ( COX 1 / COX 2 ) differed markedly between the two systems . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Most non steroidal anti inflammatory drugs ( NSAIDs ) are more potent at inhibiting Cox 1 than Cox 2 . ^^^ Indomethacin at a single oral dose ( 25 mg ) inhibited approximately 90 % the whole blood Cox 2 and Cox 1 activities ex vivo in healthy subjects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have examined the expression of the two isoforms of this enzyme , COX 1 and COX 2 , their regulation by tetradecanoyl phorbol acetate ( TPA ) , and the associated PGE 2 production in two human breast cancer cell lines with different biological phenotypes . ^^^ Estrogen dependent MCF 7 cells exhibited a relatively high expression of COX 1 ; COX 2 was barely detectable but was transiently induced by treatment with TPA ( 10 nM ) . ^^^ In contrast , the estrogen independent , highly invasive , metastatic MDA MB 231 cell line showed a low expression of COX 1 but a high constitutive level of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin blocks the constitutive ( COX 1 ) and inducible ( COX 2 ) forms of cyclo oxygenase , and is therefore nonspecific in its action . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive and upregulated constitutive COX ( COX 1 ) expression and inducible COX ( COX 2 ) expression are important in PGI 2 production required for the physiologic and pathologic defense of blood vessels and blood fluidity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is now known that there are 2 structurally distinct forms of the cyclo oxygenase enzyme ( COX 1 and COX 2 ) . ^^^ COX 1 is a constitutive member of normal cells and COX 2 is induced in inflammatory cells . ^^^ Inhibition of COX 2 activity represent the most likely mechanism of action for NSAID mediated analgesia , while the ratio of inhibition of COX 1 to COX 2 by NSAIDs should determine the likelihood of adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) consists of two isozymes , COX 1 and COX 2 . ^^^ We investigated messenger RNA expression of the COX 1 and COX 2 genes in the gastrointestinal cancer cell lines MKN 28 , MKN 45 , KATO 3 CACO 2 , DLD 1 and LoVo . ^^^ These cell lines expressed comparable levels of COX 1 mRNA , although their expression of COX 2 varied . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Unlike cyclooxygenase 2 ( COX 2 ) , COX 1 has never been identified , purified or cloned in a non mammalian species . ^^^ Sequence comparison showed this putative COX 1 to be evolutionarily less conserved than COX 2 . ^^^ The identification of an avian COX 1 shows that COX 1 and COX 2 existed as separate catalysts for prostaglandin synthesis before the divergence of birds and mammals . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We designed this study to clarify the functional relationship between this impaired cytochrome c oxidase activity and possible structural alterations to the mitochondrial genes cox 1 , cox 2 and cox 3 that encode three subunits of the cytochrome c oxidase . ^^^ In Northern blot analysis , we detected two different cox 3 transcripts and a reduced level of a cox 2 transcript , whereas we could not detect a transcript of cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 expression is largely constitutive , COX 2 is highly regulated by cytokines , growth factors , and tumor promoters , such as the protein kinase C ( PKC ) activator , phorbol 12 myristate 13 acetate ( PMA ) . ^^^ Nevertheless , phosphorylation of both human recombinant COX 1 and COX 2 by rat brain PKC in vitro was minimal , as was phosphorylation of peptides based on PKC consensus sequences in COX 1 ( less than 4 % of the phosphorylation of the PKC alpha pseudosubstrate peptide ) . ^^^ Specific polyclonal antibodies raised against sequences of human COX 1 ( Ala 24 Cys35 ) and COX 2 ( Asn 580 Lys598 ) were used for immunoprecipitation . ^^^ Neither COX 1 nor COX 2 was phosphorylated in vivo , irrespective of the presence of a phosphatase inhibitor ( 1 microM okadaic acid ) . ^^^ Although COX 1 and COX 2 are differentially regulated , no differences were observed in terms of susceptibility to phosphorylation by PKC either in vitro or in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H 2 : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of COX have been identified : COX 1 , which is constitutively expressed in most tissues and organs , and COX 2 , which is an inducible enzyme and is localized primarily in inflammatory cells and tissues . ^^^ We investigated the role of COX 1 and COX 2 in the spinal nociceptive transmission during the rat formalin test and the hot plate test using indomethacin , a non selective COX 1 and COX 2 inhibitor , and NS 398 , a selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been described in mammalian cells , referred to as cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^ COX 1 is a constitutively expressed enzyme ; COX 2 is an inducible enzyme that appears to be expressed in inflamed tissue and following exposure to growth factors or cytokines , such as interleukin 1 ( IL 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Presently , whether inhibition of COX 1 or COX 2 is required for the protective effect of aspirin and other NSAIDs is unclear . ^^^ Drugs are currently being developed that preferentially inhibit either COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Northern blot analysis showed that 3 h of acute hypoxia were sufficient to increase COX 2 but not COX 1 transcripts in the lung . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of the membrane protein COX are known : COX 1 , which is constitutively expressed in most tissues , is responsible for the physiological production of prostaglandins ; and COX 2 , which is induced by cytokines , mitogens and endotoxins in inflammatory cells , is responsible for the elevated production of prostaglandins during inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Administration of both enantiomers produced marked , time dependent inhibition of synthesis of serum thromboxane B 2 and exudate prostaglandin E 2 , indicating non selective inhibition of cyclo oxygenase ( COX ) isoenzymes COX 1 and COX 2 respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We cloned guinea pig cDNAs for cyclooxygenase 2 ( COX 2 ) , 15 hydroxyprostaglandin dehydrogenase ( PGDH ) that converts PGF 2 alpha to biologically inactive 13 , 14 dihydro 15 keto PGF 2 alpha ( PGFM ) and a fragment of cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To investigate factors involved in mediating the regulation of COX 1 and COX 2 gene expression , rat endometrial stromal and epithelial cell lines , were used . ^^^ In the endometrial epithelium derived cell line , CUE P both COX 1 and COX 2 genes were expressed in a constitutive fashion . ^^^ In conclusion , the present in vivo and in vitro data indicate that decidual COX 2 , but not COX 1 , gene expression is regulated during pregnancy and implicate specific cytokines as possible inducers within the decidua . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A study was conducted to examine the expression of the mRNA for the enzymes of the eicosanoid pathways ( 5 lipoxygenase ( 5 LO ) , 5 lipoxygenase activating protein ( FLAP ) , cyclo oxygenases 1 and 2 ( COX 1 , COX 2 ) , and 15 lipoxygenase ( 15 LO ) ) in normal subjects and in patients with stable atopic asthma and stable cystic fibrosis . ^^^ METHODS : Reverse transcription polymerase chain reaction ( RT PCR ) was used to examine the expression of total RNA for 5 LO , FLAP , COX 1 , COX 2 , and 15 LO in peripheral blood polymorphonuclear cells and mononuclear cells from the three subjects groups . ^^^ COX 2 and 15 LO were undetectable in either cell type in patients with cystic fibrosis whereas COX 1 levels in polymorphs were similar to those in patients with asthma . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These enzymes catalyse the release of arachidonic acid which is then converted to prostaglandins by the cyclooxygenases ( COX 1 and COX 2 ) . ^^^ We have used a human epithelial like cell line ( A 549 ) as a model system to study mRNA expression of sPLA 2 , cPLA 2 , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The immediate phase of PGD 2 generation was completely abrogated by the irreversible inhibition of pre existing COX 1 by aspirin pretreatment , whereas the delayed phase of PGD 2 generation was almost undetectable in the presence of the COX 2 inhibitor NS 398 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Slot blot analysis of cyclooxygenase 1 ( Cox 1 ) and Cox 2 demonstrated a decrease in both Cox 1 ( 29 % ) and , to a greater extent , Cox 2 ( 65 % ) protein expression after BFS stimulation . ^^^ When competitive polymerase chain reaction ( PCR ) was used , the peak levels of Cox 1 and Cox 2 messenger ribonucleic acid ( mRNA ) in unstimulated PMOs were 0 . 304+ / 0 . 13 pmol / L and 9 . 61+ / 2 . 84 pmol / L ( mean+ / SEM , n = 3 ) , respectively . ^^^ After exposure of samples to BFS for 30 minutes , the level of Cox 2 mRNA was reduced to 0 . 59+ / 0 . 449 pmol / L ( 16 fold reduction , p < 0 . 05 ) , and the level of Cox 1 mRNA was reduced to 0 . 02+ / 0 . 002 pmol / L ( 15 fold reduction , p < 0 . 05 ) . ^^^ These results indicate that prostaglandin production in PMOs is regulated by alterations in both immunoreactive Cox 1 and Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These include tests for the selectivity of known nonsteroidal antiinflammatory drugs ( NSAIDs ) on the constitutive enzyme of cyclooxygenase ( COX 1 ) compared with the inducible enzyme COX 2 . ^^^ Results with isolated COX 1 and COX 2 isozymes confirmed the known higher efficacy of S ( + ) compared with R ( ) ibuprofen . ^^^ In addition , the S ( + ) form has a several times lower potency with COX 2 than with COX 1 . ^^^ These data were evaluated in platelets containing mainly the constitutive COX 1 , with interleukin 1 , pretreated , rat mesangial cells which almost exclusively express COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Intrapleural injection of carrageenan in rats increased prostaglandin E 2 ( PGE 2 ) production and induced newly synthesized cyclooxygenase 2 ( COX 2 ) in pleural exudate cells without affecting COX 1 levels . ^^^ Only COX 1 , and nc COX 2 , was detected in gastric mucosal cells , and PGE 2 concentration of gastric mucosa was significantly decreased by indomethacin and ibuprofen . ^^^ This supports the hypothesis that inhibition of COX 1 causes unwanted side effects and inhibition of COX 2 produces anti inflammatory effects . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Lipopolysaccharide ( LPS ) stimulated prostaglandin E 2 ( PGE 2 ) formation and induction of cyclooxygenase 2 ( COX 2 ) expression without changing the levels of COX 1 protein in rat peritoneal macrophages . ^^^ NSAIDs inhibited PGE 2 production from exogenous AA mediated by both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pharmacological studies showed that formation of PGE 2 was mediated predominantly by COX 2 , PGD 2 by COX 1 , and TXB 2 by both COX 1 and COX 2 depending upon the timing of LPS stimulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND & AIMS : The role of two forms of cyclooxygenase ( COX 1 and COX 2 ) in gastric mucosal lesions is not well understood . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , the effect of mercaptoethylguanidine ( MEG ) and related compounds on the activity of the constitutive ( COX 1 ) and the inducible COX ( COX 2 ) was investigated in cells and in purified enzymes . ^^^ Immunostimulation of the J 774 macrophages by endotoxin ( lipopolysaccharide of E . coli , LPS 10 micrograms ml 1 ) and interferon gamma ( IFN gamma , 100 u ml 1 ) for 6 h resulted in a significant induction of COX 2 , and a down regulation of COX 1 . ^^^ In addition , the effect of mercaptoalkylguanidines on purified COX 1 and COX 2 activities was also studied . 3 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At present , two distinct isoforms of PGH 2 synthase / COX have been identified : COX 1 and COX 2 . ^^^ In many systems , COX 1 is a constitutively expressed isoform that is responsible for normal physiological production of PGs , whereas COX 2 is an inducible isoform that responds to cytokines , endotoxin and growth factors by producing high levels of PGs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this model , inhibition of COX 1 is thought to produce the undesirable side effects of NSAID therapy , whereas inhibition of COX 2 is thought to be responsible for the anti inflammatory effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) are described : COX 1 is a constitutive enzyme and is widely expressed in most tissues , COX 2 is an inducible enzyme and is abundant throughout the gastrointestinal tract . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Roles of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
New research has revealed that PG are synthesized by 2 forms of the enzyme cyclooxygenase , COX 1 and COX 2 . ^^^ Since COX 1 generally produces PG responsible for cytoprotective functions and COX 2 produces PG in inflammatory reactions , it is a reasonable hypothesis that drugs that are selective inhibitors of COX 2 should be effective antiinflammatory agents with few toxic side effects . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the pivotal enzyme in PG biosynthesis , exists in 2 isoforms : constitutive COX 1 , which produces the PG required for maintenance of normal cell activity ( e . g . , gastric cytoprotection ) , and COX 2 , which is induced in restricted tissue specific fashion ( e . g . , by inflammatory stimuli ) . ^^^ The antiinflammatory action of NSAID may result from inhibition of COX 2 , whereas their gastric side effects may result in large part from inhibition of COX 1 ; thus , a preferred NSAID should inhibit COX 2 but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive cyclooxygenase ( cox 1 mRNA ) and inducible cyclooxygenase ( cox 2 mRNA ) synthesis were unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The IC 50 values on cyclooxygenase 2 ( COX 2 ) in intact cells determined by different authors have been successfully correlated with respective IAM parameters , whereas no correlation was found with COX 1 activity data . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Inhibition of constitutively expressed cyclooxygenase ( Cox 1 ) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti inflammatory drugs ( NSAID ) , while their therapeutic action may be due to inhibition of the enzyme Cox 2 , which is specifically expressed at sites of inflammation . ^^^ METHODS : We assessed the gastrointestinal tolerability of flosulide ( 20 mg twice a day ) , a highly selective Cox 2 inhibitor with that of naproxen ( 500 mg twice a day ) , which has equal affinity for Cox 1 and 2 in 19 patients with osteoarthrosis in a randomized , double blind , crossover endoscopy study . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This amino acid effect is shown in all protein coding genes in the mitochondrial genome , including cox 1 , cox 2 , and cyt b , mitochondrial genes which are commonly used for phylogenetic studies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Vanadate also stimulated an increase in COX 2 protein levels , but did not affect significantly the levels of constitutively expressed COX 1 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGs are synthesized from arachidonate by either of two cyclooxygenases , cyclooxygenase 1 ( Cox 1 ) or cyclooxygenase 2 ( Cox 2 ) , which are present in a wide variety of mamalian cells . ^^^ Cox 1 is thought to be a constitutively expressed enzyme , and the expression of Cox 2 is inducible by cytokines or other stimuli in a variety of cell types . ^^^ Indomethacin , an inhibitor of Cox 1 and Cox 2 , further reduced the number of surviving crypts in irradiated mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of structural modification of enol carboxamide type nonsteroidal antiinflammatory drugs on COX 2 / COX 1 selectivity . ^^^ In subsequent screening in microsomal assays using human COX 1 and COX 2 , we discovered that it possessed a selectivity profile for COX 2 superior to piroxicam and other marketed NSAIDs . ^^^ While a few examples were found with greater potency in the COX 2 assay , no compound tested had a better COX 2 / COX 1 selectivity profile than that of 5 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cerebral vessels were fixed in 4 % formalin and paraffin embedded , and constitutive and inducible COX ( COX 1 and COX 2 , respectively ) levels were assessed using indirect immunofluorescence . ^^^ CONCLUSIONS : We concluded that anoxic stress increases COX 2 but not COX 1 levels in cerebral endothelium . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been characterized , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of at least 2 cyclo oxygenase ( COX ) isoenzymes , referred to as COX 1 and COX 2 , has updated our knowledge of nonsteroidal anti inflammatory drugs ( NSAIDs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of cyclooxygenases : COX 1 ( a constitutive form ) and COX 2 ( an inducible form ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This stimulation was accompanied by increased expression of inducible enzymes , NO synthase , and Cox 2 , contrasting with no variation in constitutive Cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunohistochemical studies demonstrated that cox 1 was localized in both epithelial and stromal cells , whereas cox 2 was localized solely in the luminal epithelium and to a lesser extent in the superficial glands . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis showed that the inducible cyclooxygenase enzyme ( COX 2 ) was expressed only in IL 1 beta treated cells , whereas the constitutive isoform of cyclooxygenase ( COX 1 ) remained unaltered . ^^^ The close parallelism between the kinetics of COX 2 protein expression and PGE 2 accumulation , as well as the constitutive nature of COX 1 isoform , indicate that IL 1 beta driven PGE 2 formation in human bronchial smooth muscle cells is mediated by de novo expression of COX 2 enzyme . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is expressed constitutively , whereas COX 2 is expressed in response to pro inflammatory stimuli . ^^^ COX 1 and COX 2 protein were measured by Western blot analysis with specific antibodies for COX 1 and COX 2 . ^^^ Under control culture conditions HASM cells expressed COX 1 , but not COX 2 , protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In CHO cells stably transfected with human COX isozymes , DFU inhibited the arachidonic acid dependent production of prostaglandin E 2 ( PGE 2 ) with at least a 1 , 000 fold selectivity for COX 2 ( IC 50 = 41 + / 14 nM ) over COX 1 ( IC 50 > 50 microM ) . ^^^ Indomethacin was a potent inhibitor of both COX 1 ( IC 50 = 18 + / 3 nM ) and COX 2 ( IC 50 = 26 + / 6 nM ) under the same assay conditions . ^^^ The results indicate that COX 1 inhibitory effects can be detected for all selective COX 2 inhibitors tested by use of a sensitive assay at low substrate concentration . ( ABSTRACT TRUNCATED ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The isoforms of NOS and COX responsible for metabolite release were characterized pharmacologically by use of inhibitors and at the molecular level by reverse transcription polymerase chain reaction with specific primers for iNOS , eNOS , COX 1 and COX 2 . ^^^ In separate experiments the role of the endothelium in the release of nitrite , nitrate and prostaglandins and in the expression of iNOS , eNOS , COX 1 and COX 2 was determined by comparing responses in endothelium denuded and endothelium intact segments of rat aorta . 3 . ^^^ In freshly prepared tissue , mRNAs for eNOS , COX 1 , iNOS and COX 2 were detected . ^^^ After 24 h in culture , there was an apparent increase in the level of mRNAs for iNOS and COX 2 but not for eNOS or COX 1 , an effect that was further enhanced when LPS was included in the culture medium . ^^^ The expressions of mRNA for eNOS , COX 1 , iNOS or COX 2 were not greatly different in vessels with intact or disrupted endothelium . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Platelet microparticles can also induce expression of COX 2 and prostacyclin ( PGI 2 ) production , but not expression of COX 1 , in human endothelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been characterized , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : The purpose of this study was to evaluate the expression of prostaglandin E 2 ( PGE 2 ) and the two cyclooxygenase isoforms ( cox 1 and cox 2 ) in human abdominal aortic aneurysm ( AAA ) tissue . ^^^ An immunohistochemical analysis for PGE 2 was performed , as was in situ hybridization for cox 1 and cox 2 on tissue sections . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 2 inhibitors NS 398 and nimesulide only slightly inhibited PGE 2 production , whereas the COX 1 / COX 2 inhibitors indomethacin , piroxicam and tenoxicam strongly inhibited PGE 2 production . ^^^ After the macrophages were treated with aspirin to inactivate existing COX 1 and COX 2 , however , treatment with 12 0 tetradecanoylphorbol 13 acetate increased PGE 2 production . ^^^ Furthermore , COX 2 protein levels were markedly increased by 12 0 tetradecanoylphorbol 13 acetate treatment , whereas COX 1 protein levels did not change . ^^^ In this case , both the COX 2 and the COX 1 / COX 2 inhibitors inhibited PGE 2 production . ^^^ Effects of auranofin on COX 1 dependent and COX 2 dependent PGE 2 production were examined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of COX 2 leads to the therapeutically desired inhibition of the synthesis of pro inflammatory PGs , but at the same time produces side effects associated with inhibition of COX 1 and the consequent suppression of the production of PGs necessary for normal cellular functions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX ) , the enzyme responsible for the conversion of arachidonic acid ( AA ) to prostaglandin H 2 ( PGH 2 ) , exists in two forms , termed COX 1 and COX 2 which are encoded by different genes . ^^^ Treatment of the cells with PMA induced a time dependent increase in the expression of both COX 1 and COX 2 mRNAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX ) is a rate limiting enzyme that converts arachidonic acid to prostaglandins ( PGs ) and exists in two isoforms , COX 1 and COX 2 . ^^^ Overall , the results suggest that the uterine COX 1 gene is influenced by ovarian steroids , while the COX 2 gene is regulated by the implanting blastocyst during early pregnancy . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In mouse osteoblastic cells , both IL 1alpha and IL 6 with sIL 6R markedly induced messenger RNA expression of COX 2 , but not COX 1 , as determined by Northern blot analysis , and luciferase activity in cells stably transfected with a COX 2 promoter luciferase fusion construct . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Diarylpyrrole 1 is a very potent ( COX 2 , IC 50 = 60 nm ) and selective ( COX 1 / COX 2 = > 1700 ) inhibitor whereas the isomeric 2 is completely inactive against COX 2 . ^^^ Modifications of the substituents on the fluorophenyl ring in 1 yields very potent inhibitors of COX 2 ( IC 50 = 40 80 nm ) with excellent selectivity ( 1200 to > 2500 ) vs COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study we standardized a technique to determine the IC50S of cyclooxygenase inhibitors on recombinant human COX 1 and COX 2 expressed in mammalian cells and used it to study the compounds tenoxicam , aspirin and indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compound 19a also showed potent inducible cyclooxygenase ( COX 2 ) inhibitory activity ( IC 50 = 0 . 24 microM ) with no COX 1 inhibition even at 100 microM . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using rat models for SD and focal ischemia we investigated the expression of cyclooxygenase 1 ( COX 1 ) , the constitutive form , and cyclooxygenase 2 ( COX 2 ) , the inducible form of a key enzyme in prostaglandin biosynthesis and the target enzymes for nonsteroidal anti inflammatory drugs . ^^^ Whereas COX 1 mRNA levels were undetectable and uninducible , COX 2 mRNA and protein levels were rapidly increased in the cortex , especially in layers 2 and 3 after SD and transient focal ischemia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study demonstrates that human cultured ASM cells release prostanoids in response to IL 1 beta stimulation and that the response is mostly mediated by the induction of COX 2 rather than COX 1 isoenzyme , implying that airway smooth muscle may be an important source of prostaglandins in human airways and that COX 2 may play an important role in the regulation of the inflammatory process in asthma . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Firstly NSAIDs , which act by inhibiting the enzymes that synthesise prostaglandins , cyclooxygenases ( COX 1 , COX 2 ) , but which also act upon lipo oxygenases : Their efficacy is interesting , although somewhat limited by both their ceiling effect and the frequent adverse gastrointestinal reactions they produce . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It was recently found that there are two enzymes which can form prostaglandins : COX 1 and COX 2 . ^^^ Whereas COX 1 is normally expressed in many tissues , expression of COX 2 can be induced in response to inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
EPA treatment did not alter the amount of COX 1 and COX 2 protein in VSMC . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Under this condition HL 60 cells up regulated COX 1 and COX 2 mRNA , whereas endothelial mRNA levels did not change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This year many papers have been published speculating about those NSAIDs that are reported to selectively inhibit the isoform of the cyclooxygenase enzyme that is induced in inflammatory conditions ( Cox 2 ) rather than that associated with normal physiologic function ( Cox 1 ) . ^^^ Reports have shown that the more Cox 2 selective NSAIDs ( from three to 10 fold more selective for Cox 2 over Cox 1 ) seem to have less gastrointestinal toxicity associated with their use ; however , little evidence has yet emerged from phase 1 , 2 , or 3 studies about the clinical effects of the highly selective Cox 2 inhibitors ( 300 fold or more selective for Cox 2 over Cox 1 ) . ^^^ In addition , intriguing animal studies have shown the effects of knockout of the genes controlling the activities of either Cox 1 or Cox 2 in mice . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These prostaglandins were produced via COX 1 , which like COX 2 , is induced by endotoxin administration . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX exist , COX 1 , which is constitutively expressed , and COX 2 , which is an inducible isoform . ^^^ It is thought that the antiinflammatory actions of NSAIDs are caused by the inhibition of COX 2 , whereas the unwanted side effects , such as gastrointestinal and renal toxicity , are caused by the inhibition of the constitutively expressed COX 1 . ^^^ Individual NSAIDs show different selectivities against the COX 1 and COX 2 isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It has recently been postulated that NSAIDs ' antiinflammatory efficacy arises from inhibition of the COX 2 isoform of cyclooxygenase , whereas inhibition of the COX 1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Thus , the selectivity of NSAIDs against COX 2 relative to COX 1 may provide a means of differentiating between them according to their risk of toxicity at therapeutic doses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 1 is a constitutive enzyme present at all times and is thought to produce the cytoprotective prostaglandins , COX 2 represents the inducible form of cyclooxygenase leading to production of proinflammatory prostaglandins . ^^^ A biopsy was taken from the most affected area . mRNAs for COX 1 and COX 2 were detected using reverse transcription polymerase chain reaction . ^^^ RESULTS : The fraction of patients demonstrating COX 2 mRNA significantly increased with increasing disease activity ( p < 0 . 005 ) , whereas the fraction of patients demonstrating COX 1 mRNA remained unchanged ( p > 0 . 05 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the enzyme responsible for prostanoid production , exists as two isoforms : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mice have been prepared that lack expression of COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study assessed the hypothesis that PVT increases Kupffer cell PGE 2 production via up regulation of Kupffer cell phospholipase A 2 ( PLA 2 ) as well as constitutive ( COX 1 ) and inducible ( COX 2 ) cyclooxygenase . ^^^ Kupffer cells from PVT treated rats were then cultured in the presence of inhibitors of PLA 2 , COX 1 , or COX 2 . ^^^ When Kupffer cells were treated with mepacrine to inhibit PLA 2 ( 5575+ / 453 pg / ml ) , PGE 2 production was not different from that by PVSal treated controls ( 6467+ / 614 pg / ml ) , but when Kupffer cells were incubated in the presence of the COX 1 inhibitor flurbiprofen ( 3512+ / 407 pg / ml ) or the COX 2 inhibitor nimesulide ( 2800+ / 830 pg / ml ) , production was decreased 46 . 7 % and 56 . 7 % , respectively , over control activity without added inhibitor . ^^^ PVT also increased Kupffer cells COX 1 and COX 2 mRNA as measured by Northern blot . ^^^ In summary , PVT increased Kupffer cell PGE 2 production , up regulated transcription of Kupffer cells COX 1 and COX 2 mRNA , and prolonged cardiac allograft survival . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of COX have been identified , COX 1 ( constitutive form ) and COX 2 ( a form highly inducible in response to inflammatory stimuli ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin synthesis requires cyclooxygenase 1 ( COX 1 ) or 2 ( COX 2 ) , which mediate the conversion of arachidonate to prostaglandin H 2 . ^^^ COX 1 is the predominant constitutive isoform , whereas COX 2 expression is typically low . ^^^ In cultured medullary interstitial cells , COX 2 mRNA predominated , with little COX 1 expression . ^^^ Interstitial cell COX 2 mRNA but not COX 1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At the doses employed , celecoxib inhibited only COX 2 and not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 tissue expression : implications and predictions . ^^^ One would predict , based on current information regarding the differential tissue expression of COX 1 and COX 2 , that highly selective inhibitors of COX 2 will provide effective antiinflammatory activity with marked reduction in toxicity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because COX 2 inhibitors do not inhibit COX 1 isoenzyme activity at pharmacologic concentrations , they are devoid of many of the toxicities that are typical side effects of NSAID . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) isoform expression , intracellular localization , and function in endothelial cells from the newborn pig cerebral microvessels were investigated using COX 1 and COX 2 specific antibodies and the COX 2 inhibitor NS 398 . ^^^ Cerebral microvessels , microvascular endothelium , and cultured endothelial cells constitutively express both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition to constitutive COX 1 , inducible COX 2 has been discovered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tranilast did not affect constitutive cyclooxygenase ( COX 1 ) or COX 2 activity in non stimulated or IL lbeta stimulated fibroblasts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Incubation of anandamide with lysates and the intact cell line expressing COX 2 but not that of COX 1 produced prostaglandin E 2 ethanolamide . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To determine if a cause and effect relationship exists between Cox isoenzyme overexpression and tumorigenesis , the human Cox 1 and Cox 2 isoenzymes were transfected into ECV immortalized endothelial cells . ^^^ Although numerous clones of Cox 1 expressing cells were obtained , Cox 2 overexpression resulted in growth disadvantage and increased cell death . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ex vivo inhibition of cyclooxygenase product synthesis ( prostaglandin E 2 , thromboxane B 2 ) in whole blood was used as an indicator of activity for the constitutive COX 1 isoform , although inhibition of the synthesis of these mediators in the chamber exudate during an inflammatory process is believed to represent COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Aspirin is an approximately 150 to 200 fold more potent inhibitor of the ( constitutive ) isoform of the platelet enzyme ( COX 1 ) than the ( inducible ) isoform ( COX 2 ) which is expressed by cytokines , inflammatory stimuli , and some growth factors . ^^^ This explains the different dosage requirements of aspirin as an antithrombotic ( COX 1 ) and an anti inflammatory drug ( COX 2 ) , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) isoforms COX 1 and COX 2 convert arachidonic acid to prostaglandin ( PG ) precursors and are a limiting step in PG production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Animals were sacrificed 1 , 12 , or 36 weeks after the last AOM or saline injection , and their colonic mucosa , as well as the grossly visible colon tumors from rats sacrificed 36 weeks after the last AOM injection , were analyzed for the expression levels of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Newly developed NSAIDs , highly selective for cyclo oxygenase 2 ( COX 2 ) , may exert potent anti inflammatory effects without affecting COX 1 or the gastrointestinal mucosa . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Of the two Cox isoforms , Cox 1 is constitutively expressed in nearly all cells ; whereas Cox 2 is induced by a wide range of ligands . ^^^ Analysis of accumulated and de novo synthesis of constitutive Cox 1 and inducible Cox 2 proteins showed no age related difference in Cox 1 protein levels , but Mphi from old mice had higher accumulated and newly synthesized LPS stimulated Cox 2 protein levels than young mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two genetically distinct isoforms have been discovered , COX 1 and COX 2 . ^^^ While COX 1 is thought to account for homeostatic amounts of eicosanoids , COX 2 is induced during inflammation leading to pathologic amounts of eicosanoids . ^^^ Since NSAIDs inhibit both COX isoforms , antiinflammatory drug research has refocused to discovering COX 2 inhibitors that do not inhibit COX 1 . ^^^ For this purpose , we have developed a whole cell assay system using the human erythroleukemic cell line HEL as a source for COX 1 and the human monocytic cell line Mono Mac 6 as a source for COX 2 . ^^^ Mono Mac 6 cells express high amounts of COX 2 upon stimulation with lipopolysaccharide ( LPS ) in the absence of any detectable COX 1 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both cyclo oxygenase isoforms ( COX 1 and COX 2 ) may also form free 8 epi PGF 2 alpha as a minor product . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In in vitro experiments , indometacin inhibited COX 1 about 1 . 7 times more potently than COX 2 . ^^^ NS 398 inhibited COX 2 with an IC 50 of 0 . 32 microM , but never affected COX 1 activity , even at 100 microM . ^^^ In the same assay system , meloxicam inhibited COX 2 about 12 times more selectively than COX 1 . ^^^ One reason for its in vivo pharmacological profile may be related to its relative selectivity for COX 2 over COX 1 . ^^^ Thus , meloxicam may belong to a group of COX 2 selective anti inflammatory agents with a better safety profile than conventional COX 1 and COX 2 nonselective anti inflammatory agents . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The message encoding COX isoenzymes ( constitutive COX 1 and inducible COX 2 ) have been described in the rat kidney . ^^^ The presence of COX 2 in TAL ( a tubular segment postulated to be devoid of COX 1 ) may contribute to the handling of ions through local production of prostaglandins . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Northern blot analysis was performed to quantify cyclooxygenase COX 1 ( constitutive ) , COX 2 ( inducible ) and phospholipase A 2 ( PLA 2 ) messenger RNA ( mRNA ) production in response to treatment . ^^^ The results indicate that roIFN tau treatment did not affect COX 1 and PLA 2 mRNA production in either cell type , whereas COX 2 expression was upregulated in both . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two cyclooxygenase ( Cox ) enzymes , Cox 1 and Cox 2 , that are responsible for initiating PGE 2 synthesis . ^^^ This report examines differences in the roles of Cox 1 and Cox 2 in regulating cytokine synthesis in macrophages . ^^^ This effect was specifically linked to activation of Cox 2 and not Cox 1 . ^^^ The experimental findings demonstrate that the effects of Cox 1 and Cox 2 activity on macrophage IL 6 synthesis are segregated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The key enzymes are cytosolic phospholipase A 2 ( cPLA 2 , Mr 85 , 000 ) and the cyclo oxygenases ( COXs ) which exist in constitutive ( COX 1 ) and inducible forms ( COX 2 ) . ^^^ In human stomach tumours and associated macroscopically normal tissues , we determined the fatty acid composition by gas chromatography , amounts of cPLA 2 , COX 1 and COX 2 by immunoblotting with specific antibodies and cPLA 2 enzyme activity using a tritiated substrate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is the rate limiting enzyme in the synthesis of prostaglandins ( PGs ) and exists in two isoforms , COX 1 and COX 2 . ^^^ We demonstrate herein that the targeted disruption of COX 2 , but not COX 1 , in mice produces multiple failures in female reproductive processes that include ovulation , fertilization , implantation , and decidualization . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , partial bovine COX 1 ( 777 pb ) and COX 2 ( 449 bp ) cDNAs were cloned and sequenced . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An expanding body of evidence indicates that downregulation of the cyclooxygenases ( Cox 1 and Cox 2 ) will be an important strategy for preventing cancer because cyclooxygenases catalyze the formation of prostaglandins ( PGs ) , and PGs have multiple effects that favor tumorigenesis . ^^^ This is important because simultaneous inhibition of Cox 1 ( constitutively expressed ) and Cox 2 ( inducible isoform ) , which is achieved with classical NSAIDs , interferes with the housekeeping functions of Cox 1 and thereby causes serious side effects , such as peptic ulcer disease . ^^^ Simultaneous inhibition of Cox 1 and Cox 2 hence is not a realistic approach for chemoprevention in individuals at low to moderate risk for cancer . ^^^ Through understanding the biochemistry of these enzymes and the regulation of Cox 1 and Cox 2 gene expression , we review how Cox 2 can be regulated selectively as a target for chemopreventive therapy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cortical COX 2 mediated prostaglandin formation is probably important in low salt states whereas medullary COX 1 produced prostaglandins seem to be more important for renal adaptation to a high salt intake . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pretreatment with indomethacin ( 10 mg kg [ 1 ] , s . c . ) , a nonselective COX 1 and COX 2 inhibitor , attenuated the gastric hyperaemic response caused by TC without affecting p . d . and acid loss , resulting in haemorrhagic lesions in the mucosa . ^^^ The expression of COX 1 mRNA was consistently detected in the gastric mucosa before and after TC treatment , while a faint expression of COX 2 mRNA was detected only 2 h after TC treatment . 5 . ^^^ These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC induced barrier disruption , and suggest that COX 1 but not COX 2 is a key enzyme in maintaining ' housekeeping ' functions in the gastric mucosa under both normal and adverse conditions . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pathological analyses and measurements of lipid peroxidation , tumor necrosis factor ( TNF ) alpha , COX 1 and COX 2 messenger RNA ( mRNA ) , endotoxin , and liver and plasma thromboxane were performed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study supports a mediator role for endogenous PGs in duodenal HCO 3 secretion in response to mucosal acidification and suggests that COX 1 but not COX 2 is a key enzyme in regulating this process and maintaining the mucosal integrity against acid in the duodenum . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ibuprofen , a cyclooxygenase ( COX ) inhibitor nonselective for either COX 1 or COX 2 isoform , upregulates cerebrovascular prostaglandin E 2 ( PGE 2 ) and PGF2alpha receptors in newborn pigs . ^^^ Hence , we determined PGE 2 and PGF2alpha receptor density and functions in brain vasculature by using newborn pigs treated with saline , ibuprofen , COX 1 inhibitor ( valerylsalicylate ) , or COX 2 inhibitors ( DUP 697 and NS 398 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Studies were undertaken to assess expression of inducible cyclooxygenase ( COX ) 2 in bladder during fetal development and COX 1 and COX 2 expression after outlet obstruction . ^^^ In adult bladder , both COX 1 and COX 2 were detectable at low levels under basal conditions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There is now convincing evidence , obtained with a number of structurally distinct inhibitors , that selective COX 2 inhibitors possess anti inflammatory effects with an improved gastrointestinal tolerability compared with conventional nonsteroidal anti inflammatory drugs ( NSAIDs ) affecting both COX 1 and COX 2 . ^^^ As more selective COX 2 inhibitors are being developed , assays with a high degree of sensitivity to inhibition are needed to compare the relative effects of compounds on COX 1 activity . ^^^ Among the compounds that have been reported to show selectivity for COX 2 , the rank order of potency against COX 1 was DuP 697 > SC 58451 > celecoxib > nimesulide meloxicam piroxicam NS 398 RS 57067 > SC 57666 > SC 58125 > flosulide > etodolac > L 745 , 337 > DFU T 614 , with IC 50 values ranging from 7 nM to 17 microM . ^^^ However , the microsomal assay was more sensitive to inhibition than cell based assays and allowed the detection of inhibitory effects on COX 1 for all NSAIDs and selective COX 2 inhibitors examined with discrimination of their potency under conditions of limited availability of arachidonic acid . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we investigated expression of the two isoforms of the prostaglandin forming enzyme , cyclooxygenase 1 ( Cox 1 ) and cyclooxygenase 2 ( Cox 2 ) , in sheep embryos . ^^^ Using Western blot and immunohistochemical analyses , we demonstrated that Cox 2 was highly expressed in embryos from Day 8 to Day 17 of development whereas Cox 1 was undetectable during this time . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Calcium ionophore dependent PGE 2 synthesis was associated with COX 2 expression , whereas COX 1 and COX 2 seemed to participate in arachidonic acid dependent PGE 2 synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inducible form of cyclooxygenase 2 ( COX 2 ) but not of the constitutive form COX 1 was implicated in the generation of both PGE 2 and PGD 2 in these cells by use of specific inhibitors and effects of dexamethasone . ^^^ Neither COX 1 nor COX 2 protein levels were affected by TNFalpha or PKA activators used alone , whereas in association , marked up regulation of COX 2 mRNA and protein was observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , we investigated the expression of COX 1 and COX 2 in human placenta and placental bed . ^^^ COX 1 and COX 2 were localized immunohistochemically with the identification of positive cells by double immunofluorescence staining . ^^^ Expression of both COX 1 and COX 2 could be observed in placenta and placental bed . ^^^ In placental bed , protein and mRNA levels of COX 1 were increased in the pre eclamptic group ( P < 0 . 05 ) , whereas COX 2 expression did not differ significantly from normal pregnancies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ibuprofen had no effect on constitutive COX ( COX 1 ) or inducible COX ( COX 2 ) mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These findings suggest that duodenal ulcerogenicity of IND in the presence of histamine is mainly due to the inhibitory action on acid stimulated bicarbonate secretion mediated by COX 1 , but not by COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Most available nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit both the constitutive cyclooxygenase 1 ( COX 1 ) and the inducible cyclooxygenase 2 ( COX 2 ) , resulting in inhibition of prostaglandin ( PG ) and thromboxane ( TX ) biosynthesis . ^^^ The inhibition of COX 2 might be the cause of the favourable anti inflammatory , analgesic and antipyretic effects of NSAIDs , whereas that of COX 1 might result in unwanted gastrointestinal , renal and possibly other side effects . ^^^ In several in vitro assays using either purified COX 2 and COX 1 preparations or cell preparations ( both from animal and human origins ) expressing COX 1 or COX 2 , ten out of eleven different groups have demonstrated that nimesulide selectively inhibits COX 2 . ^^^ The COX 2 / COX 1 inhibitory ratio varies , according to the assay preparation , from about 0 . 76 to 0 . 0004 i . e . a 1 . 3 to 2 , 512 fold higher selectivity for COX 2 than for COX 1 . ^^^ Moreover , an in vivo whole blood assay performed on healthy volunteers demonstrated a significant fall in COX 2 PGE 2 production without any effect on COX 1 TXB 2 production in subjects treated with nimesulide ( 100 mg b . i . d . for 2 weeks ) versus no effect on COX 2 PGE 2 and an almost total suppression of COX 1 TXB 2 in subjects treated with aspirin ( 300 mg t . i . d . for 2 weeks ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , Ca2+ ionophore stimulated immediate PGE 2 generation was regulated predominantly by the constitutive enzymes cPLA 2 and COX 1 , even when type IIA sPLA 2 and COX 2 were maximally induced after IL 1 beta / TNF alpha treatment , revealing functional segregation of the constitutive and inducible PG biosynthetic enzymes . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To compare the expression of the cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , in synovial tissue samples between patients with inflammatory arthritis ( i . e . , rheumatoid arthritis [ RA ] , ankylosing spondylitis [ AS ] , or psoriatic arthritis [ PsA ] ) and patients with osteoarthritis ( OA ) . ^^^ Paraffin embedded sections of synovial tissue from patients with OA ( n = 18 ) , RA ( n = 35 ) , AS ( n = 9 ) , and PsA ( n = 16 ) were immunostained for COX 1 and COX 2 . ^^^ In addition , samples of OA and RA synovial tissue were analyzed for levels of COX 1 and COX 2 messenger RNA ( mRNA ) using reverse transcriptase polymerase chain reaction . ^^^ The expression of COX 2 , but not the expression of COX 1 , was found to be elevated in a disease related pattern in the synovial tissue from patients with RA , AS , or PsA in comparison with OA samples , and was especially high in AS synovial tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E 2 ( PGE 2 ) and on the expression of the cyclooxygenase isoforms , COX 1 and COX 2 , in various human cell types . ^^^ Total RNA was extracted from the cells and analyzed for COX 1 and COX 2 messenger RNA ( mRNA ) expression using reverse transcriptase polymerase chain reaction or Northern blotting . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Conversion of increased arachidonic acid release to PGE 2 by COX 1 is mainly involved in the short term effect , whereas B 2 receptor related COX 2 induction is important in the long term PGE 2 release . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( Cox 1 ) and Cox 2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids . ^^^ We studied the effects of plasma HDL and LDL on the synthesis of prostacyclin , Cox 1 / Cox 2 mRNA , and protein expression by rabbit aortic smooth muscle cells . ^^^ In addition , Northern blot analyses did not reveal differences in Cox 1 mRNA levels between control and HDL treated cells , whereas Cox 2 mRNA levels were significantly increased in treated cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed and produces PGs and thromboxane A 2 during normal physiologic activities , while COX 2 is an inducible enzyme stimulated by growth factors , lipopolysaccharide , and cytokines during inflammation or cell injury . ^^^ Results presented here demonstrate that TNF alpha elicits prolonged and regulatable induction of COX 2 in WISH cells , while COX 1 is constitutively expressed and unchanged in response to TNF alpha stimulation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Polyclonal antibodies to human COX 1 and COX 2 were localized with immunoperoxidase staining . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Time course studies on the mRNA expression for c fos in the hind brain and cyclooxygenase ( COX ) isoforms in the peritoneal cells , as well as on the peritoneal 6 keto PGF1alpha accumulation , after stimulation indicated that COX 1 but not COX 2 was responsible for the peritoneal synthesis of PGs which were suggested to evoke c fos expression in the hind brain . ^^^ Pharmacological experiments using mofezolac , a preferential inhibitor against COX 1 , and NS 398 , a selective inhibitor against COX 2 , confirmed the involvement of COX 1 derived PGs in the induction of c fos expression in the hind brain following the noxious stimulation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using Northern and RT PCR analysis , we have determined in 15 control and 10 sporadic AD human neocortical samples ( age range , 60 82 yr ; postmortem interval [ PMI ] range , 0 . 7 16 . 0 hr ) the levels of COX 2 RNA in relation to the constitutively expressed COX 1 and beta actin RNA message levels . ^^^ Our results indicate that in short PMI brain , COX 1 and COX 2 transcripts are relatively low abundance RNA messages , ranging from a mean of 6 . 8 % of the beta actin signal in controls to 8 . 5 % of the beta actin signal in AD affected brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of acute systemic inflammatory response and cytokines on the transcription of the genes encoding cyclooxygenase enzymes ( COX 1 and COX 2 ) in the rat brain . ^^^ Animals were also killed at various times after intravenous administration of interleukin 1beta , tumor necrosis factor alpha , and interleukin 6 , and mRNAs encoding COX 1 and COX 2 were assayed by in situ hybridization histochemistry . ^^^ In contrast , intravenous injection of interleukin 6 did not alter genetic expression of COX 2 , and none of the above described models affected the synthesis of COX 1 gene in the rat brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The results suggest that prostaglandin modulates the febrile effects of LPS in swine and that inhibition of inducible cyclooxygenase ( Cox 2 ) suppresses fever without producing the stressful side effects that accompany constitutive cyclooxygenase ( Cox 1 ) inhibition , as exemplified by IND ( a mixed Cox 1 / Cox 2 antagonist ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 are constitutively expressed in endothelial cells from newborn pig cerebral microvessels . ^^^ Similar changes were observed in other vascular cells from newborn pigs that also express COX 1 and COX 2 ( cerebral microvascular smooth muscle cells and aortic endothelial cells ) but not in human umbilical vein endothelial cells or Swiss 3T3 fibroblasts that express COX 1 only . ^^^ COX 2 , but not COX 1 , was detected in endothelial fractions immunoprecipitated with anti phosphotyrosine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the ontogeny and cellular localization of COX 1 ( constitutive ) and COX 2 ( inducible ) gene expression in lungs from late gestation fetal lambs , 1 wk old newborn lambs ( NB 1 ) , and 1 to 4 mo old newborn lambs ( NB 2 ) . ^^^ These findings indicate that there is differential expression of COX 1 and COX 2 in the developing lung and that the enzymes are expressed in a cell specific manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Lipopolysaccharide ( LPS , 1 mg / kg , i . v . ) was administered to rats ( LPS treated rats ) and expression of COX 1 mRNA and COX 2 mRNA in the aorta and peripheral blood leukocytes was examined by RT PCR . ^^^ This approach is useful to directly analyze the inhibitory activity of NSAIDs for COX 1 and COX 2 in vivo . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A radiochemical enzyme assay for studying cyclooxygenase ( COX ) catalyzed prostaglandin biosynthesis in vitro was optimized with respect to both COX 1 and COX 2 activity . ^^^ The assay can be used to assess the relative selectivity of plant derived inhibitors on COX 1 and COX 2 Assay conditions were optimized for both enzymes with respect to concentration of cofactors ( l epinephrine , reduced glutathione , and hematin ) , activation time ( enzyme and cofactors ) , reaction time , and pH . ^^^ Quercitrin was found to be inactive toward both COX 1 and COX 2 catalyzed prostaglandin biosynthesis . ^^^ The optimization procedure resulted in a considerable reduction of the amount of enzyme required for adequate prostglandin biosynthesis and a reliable method suited to evaluate natural products on inhibition of COX 2 catalyzed prostaglandin biosynthesis , as well as on COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin E 2 ( PGE 2 ) production in immortalized , nontransformed cells derived from wild type , cyclooxygenase 1 deficient ( COX 1 ( / ) ) or cyclooxygenase 2 deficient ( COX 2 ( / ) ) mice was examined after treatment with interleukin ( IL ) 1beta , tumor necrosis factor alpha , acidic fibroblast growth factor , and phorbol ester ( phorbol myristate acetate ) . ^^^ Compared with their wild type counterparts , COX 1 ( / ) or COX 2 ( / ) cells exhibited substantially enhanced expression of the remaining functional COX gene . ^^^ Furthermore , both basal and IL 1 induced expression of cytosolic phospholipase A 2 ( cPLA 2 ) , a key enzyme regulating substrate mobilization for PGE 2 biosynthesis , was also more pronounced in both COX 1 ( / ) and COX 2 ( / ) cells . ^^^ Thus , COX 1 ( / ) and COX 2 ( / ) cells have the ability to coordinate the upregulation of the alternate COX isozyme as well as cPLA 2 genes to overcome defects in prostaglandin biosynthetic machinery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that COX 2 , and not COX 1 , gene expression is dominant in pancreatic islet tissue under both basal and IL 1 stimulated conditions . ^^^ These studies provide documentation of NF IL 6 in the pancreatic islet and that COX 2 , rather than COX 1 , is dominantly expressed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , conventional NSAIDs inhibit both cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , and cause gastrointestinal side effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase is now known to exist in two separate isoforms which are called COX 1 and COX 2 . ^^^ It is now believed that eicosanoids produced by COX 1 activity are essential for the physiological ( house keeping ) functions while those produced by COX 2 lead to various pathological changes in body tissues . ^^^ Older nonsteroidal antiinflammatory drugs like aspirin and indomethacin are non selective inhibitors of COX activity and therefore , in addition to inhibiting COX 2 activity , inhibit the formation of eicosanoids by COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Urate crystal administration reduced COX 1 , but induced COX 2 expression in peritoneal cells . ^^^ The reduction of COX 1 may contribute to the attenuation of PG synthesis after 1 and 2 h , but PG synthesis remained inhibited up to 6 h , when COX 2 levels were high . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Clinical and pharmacological value is discussed of selective blockade of cyclogenase isoenzymes ( COX ) COX 1 and COX 2 in the antiinflammatory effect and development of unfavourable side effects . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , it has been shown that COX exists in two related but unique isoforms , COX 1 and COX 2 . ^^^ We evaluated the effect of 2 papillotoxic agents , including a nonsteroidal anti inflammatory drug , indomethacin , and a chemical agent , 2 bromoethanamine hydrobromide ( 2 BEA ) , on COX 1 and COX 2 in the renal papilla as a means of assessing what changes occur in the expression of these isoforms during the development of RPN . ^^^ The immunohistochemical analyses of kidneys showed that both COX 1 and COX 2 were present in the renal papilla of control rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new non steroidal anti inflammatory drug ( NSAID ) , with a favourable ratio of inhibition of cyclooxygenase 2 ( COX 2 ) / cyclooxygenase 1 ( COX 1 ) , giving the drug the potential to produce few gastric adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The ubiquitous cyclooxygenase 1 ( COX 1 ) subserves housekeeping functions , whereas the inducible cyclooxygenase 2 ( COX 2 ) is expressed by limited cell types and tightly controlled . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One well documented target for NSAIDs is prostaglandin endoperoxide synthase ( cyclooxygenase ) and two isoforms of this enzyme have been identified , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Glomerular expression of the major rate limiting enzymes for prostanoid synthesis , cyclooxygenase isoforms ( COX 1 and COX 2 ) and cytosolic phospholipase A 2 ( cPLA 2 ) , was investigated in anti Thy 1 nephritis in rats . ^^^ Immunofluorescence microscopy , using antibodies against COX isoforms , showed that both COX 1 and COX 2 were negligible or faintly detectable in the glomeruli of control rat kidneys . ^^^ In contrast , the immunofluorescence for COX 1 was intensified on days 4 and 10 along the glomerular capillary walls probably in glomerular epithelial and / or endothelial cells , whereas COX 2 staining was exclusively enhanced in the glomerular epithelial cells at 1 h and day 10 during the course of anti Thy 1 nephritis . ^^^ These findings indicate that prostanoids generated through induction of COX 1 , COX 2 , and cPLA 2 are implicated in the mediation of the mesangial cell injury model . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Aspirin and conventional nonsteroidal anti inflammatory drugs are nonselective inhibitors of cyclooxygenase 1 ( COX 1 ) and COX 2 enzymes . ^^^ Two classes of selective COX 2 inhibitors : ( 1 ) sulfonamides , such as L 745 , 337 , and ( 2 ) tricyclic methyl sulfone derivatives , such as SC 58125 , have been developed . 10 ray crystal structures of COX 1 and COX 2 have provided valuable information regarding the structural basis for their COX 2 selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) , the key enzyme in PG synthesis , have been characterized : a constitutively expressed form , COX 1 , and an inducible form , COX 2 . ^^^ COX 1 and COX 2 mRNA expression was determined by total RNA extraction and reverse transcription polymerase chain reaction . ^^^ COX 1 and IL 1beta induced COX 2 mRNA expression were not inhibited by MTX . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although the COX 1 gene was found to be expressed at constitutively low levels , the TATA containing COX 2 gene , which contains AP 1 like , GAS , and NF kappaB DNA binding sites in its immediate promoter , was found to be strongly induced by IL 1beta or PAF ( P < 0 . 001 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Surgical specimens from 44 patients with breast cancer who had undergone lumpectomy or mastectomy were analyzed by immunoblot analysis and immunohistochemical analysis to determine the expression profile of the constitutively expressed form of cyclooxygenase ( COX 1 ) and the inducible form ( COX 2 ) ; the specimens from 14 patients included normal breast tissue . ^^^ Immunohistochemical staining of specimens that expressed COX 1 and / or COX 2 revealed that COX 1 was localized in stromal cells adjacent to the tumor but not in tumor cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase 1 ( COX 1 ) and 2 COX 2 ) . ^^^ COX 1 mRNA was present in the glomerulus and all along the collecting duct , whereas COX 2 mRNA was restricted to the macula densa containing segment ( MD ) , cortical thick ascending limb ( CTAL ) , and , at significantly lower levels , in the inner medullary collecting duct . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostanoid generation may proceed via both isoforms of cyclooxygenase , Cox 1 and Cox 2 . ^^^ Cox 1 is thought to be ubiquitously expressed , whereas Cox 2 is mostly assumed to be dynamically regulated , responding to inflammatory stimuli . ^^^ The cellular localization of Cox 1 and Cox 2 in the lung , an organ with high cyclooxygenase activity , is not known . ^^^ In normal rat lungs the expression and localization of Cox 1 and Cox 2 were examined with immunogold silver staining and the RT PCR technique . ^^^ Expression of both Cox 1 and Cox 2 was readily detectable in rat lungs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Differential effects of inhibition of isoforms of cyclooxygenase ( COX 1 , COX 2 ) in chronic inflammation . ^^^ OBJECTIVE AND DESIGN : The anti inflammatory effects of therapeutic dosing of drugs with greater selectivity for the inhibition of the constitutive ( COX 1 ) or inducible isoform ( COX 2 ) of cyclooxygenase were assessed in a model of chronic inflammation . ^^^ Aspirin , more selective in vitro for the inhibition of COX 1 ( 10 , 200 ( mg / kg ) and nimesulide , a selective in vitro inhibitor of COX 2 ( 0 . 5 , 5 mg / kg ) were dosed p . o . daily from 3 days after injection of the inflammatory stimulus . ^^^ CONCLUSION : In this model of chronic inflammation , aspirin , more selective for the inhibition of COX 1 is more effective than the selective COX 2 inhibitors nimesulide and NS 398 at inhibiting granuloma dry weight , vascularity and COX activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The level of the expression of COX 2 protein peaked at 6 h , whereas the level of COX 1 protein was not significantly changed . ^^^ The application of Gd 3 , a blocker for SA channel , or the removal of extracellular Ca2+ inhibited the production of COX 2 mRNA without any effect on the production of COX 1 or GAPDH mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To test the hypothesis that TCDD induces immune suppression by altering the production of immunomodulatory AA metabolites , we examined the effects of TCDD on splenic AA release , LTB 4 and PGE 2 production , and cox 1 and cox 2 expression . ^^^ We examined the direct induction of cox 1 and cox 2 by TCDD and the indirect induction of cox 2 via TCDD induced IL 1 . ^^^ Interestingly , exposure to TCDD did not alter message or protein levels of cox 1 , cox 2 , or IL 1 over the course of the response to P 815 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As expected , they lack mtDNA encoded subunits COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclo oxygenases 1 ( Cox 1 ) and 2 ( Cox 2 ) catalyse the conversion of arachidonic acid to prostaglandin endoperoxides , leading to the formation of prostaglandin and thromboxane mediators of inflammation . ^^^ METHODS : We studied Cox 1 and Cox 2 immunoreactivities in nasal polyp , maxillary sinus , and turbinate biopsies obtained from eight patients with chronic allergic rhinitis and sinusitis and / or nasal polyps , 15 patients with chronic non allergic rhinitis and sinusitis and / or nasal polyps and five control subjects ( patients requiring nose surgery not related to sinusitis or nasal polyps ) . ^^^ RESULTS : Both Cox and Cox 2 were mainly expressed in the epithelium ( basal , ciliated ) and were found in 16 / 28 and 25 / 28 subjects for Cox 1 and Cox 2 respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Results for RT PCR and Western blot analysis showed that COX 1 as well as an IL 1beta and TNF alpha inducible COX 2 are expressed in HT 29 Cl . 19A . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Distribution of COX 1 and COX 2 in normal and inflamed tissues . ^^^ Recently two forms of COX were identified a constitutively expressed COX 1 and a cytokine inducible COX 2 . ^^^ Potent anti inflammatory agents like the glucocorticoids are known to inhibit specifically the expression of COX 2 while commercially available NSAIDs like indomethacin inhibit both COX 1 and COX 2 . ^^^ These findings have led to the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non regulated or constitutive form of COX ( COX 1 ) , whereas therapeutic benefit derives from inhibition of the inducible enzyme , COX 2 . ^^^ We have examined the relative distribution of COX 1 and COX 2 in both normal and inflamed tissues and report that COX 1 expression dominates normal tissues while COX 2 mRNA is induced at the inflammatory site . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To extend these observations , we examined the ( R ) and ( S ) enantiomers of RS ketorolac , ( S ) ketorolac exhibited potent COX 1 and COX 2 enzyme inhibition , whereas ( R ) ketorolac was > 100 fold less active on both COX subtypes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new oxicam which has a low COX 2 / COX 1 ratio , i . e . it has an inhibitory effect focused on the inflammatory proteins ( COX 2 ) with relative saving of the homeostatic proteins ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs inhibit constitutive ( COX 1 ) and induced cyclooxygenase ( COX 2 ) , blocking prostaglandin production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase isozymes Cox 1 and Cox 2 as enzymes essential for prostaglandin biosynthesis were therefore investigated in rat spinal cord . mRNA and protein of both enzymes was detected in cervical and lumbar sections of the spinal cord of normal animals . ^^^ Enzyme activity of Cox 1 and Cox 2 could be determined by the use of specific inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Apoptosis induction and inhibition of colon 26 tumour growth and angiogenesis : findings on COX 1 and COX 2 inhibitors in vitro & in vivo and topical diclofenac in hyaluronan . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After characterization of the COX 1 enzyme in 1976 , a second COX gene was discovered in 1991 encoding for the inducible COX 2 . ^^^ The range of activities of NSAIDs against COX 1 compared to COX 2 explains the variations in the side effects of NSAIDs at their antiinflammatory doses . ^^^ Drugs which have the highest potency on COX 2 and less effect on COX 1 will have potent antiinflammatory activity with fewer side effects . ^^^ All the results published so far support the hypothesis that the unwanted side effects of NSAIDs , such as damage to the gastric mucosa and kidneys , are due to their ability to inhibit COX 1 , while their antiinflammatory ( therapeutic effects ) are due to inhibition of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Transcriptional regulation of fatty acid cyclooxygenase isozymes ( COX 1 and COX 2 ) were studied using two cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study was undertaken to determine the mechanism ( s ) by which ceramide and IL 1 interact to enhance PGE 2 production by examining their respective effects on the rate limiting enzymes in PGE 2 synthesis , cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , and cytosolic phospholipase A 2 ( cPLA 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL 1 beta induced COX 2 but not COX 1 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since then , there has been general acceptance of the concept that these drugs work by inhibition of the enzyme cyclo oxygenase ( COX ) , which we now know to have at least two distinct isoforms : the constitutive isoform , COX 1 , and the inducible isoform , COX 2 . ^^^ It is therefore attractive to suggest that the anti inflammatory actions of NSAIDs are due to inhibition of COX 2 , whereas the unwanted side effects , such as irritation of the stomach lining , are due to inhibition of COX 1 . ^^^ Drugs that have the highest COX 2 activity and a more favorable COX 2 : COX 1 activity ratio will have a potent anti inflammatory activity with fewer side effects than drugs with a less favorable COX 2 : COX 1 activity ratio . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In order to reduce the gastroduodenal side effects of NSAIDs , selective cyclo oxygenase ( COX ) 2 inhibitors have been developed , which inhibit the inducible COX 2 isoform in inflammatory tissue but have only limited effect on the constitutive COX 1 isoform in the stomach . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we examined cyclooxygenases 1 and 2 ( COX 1 and COX 2 ) and cytosolic phospholipase A 2 ( cPLA 2 ) to determine whether the rate limiting enzymes in the eicosanoid synthetic pathway are altered by ciprofibrate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Chemopreventive effects of NSAIDs against colorectal cancer : regulation of apoptosis and mitosis by COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Evidence therefore suggests that the GI toxicity associated with NSAID use is primarily the result of inhibition of COX 1 , and antiinflammatory effects are largely due to inhibition of COX 2 . ^^^ A drug that specifically inhibits COX 2 without affecting COX 1 would , theoretically , reduce inflammation without leading to GI side effects . ^^^ A variety of biologic assays have been developed to characterize the relative activities of NSAID against COX 1 and COX 2 . ^^^ Several NSAID have been reported to show more potent inhibition of COX 2 than of COX 1 in vitro ; however , the clinical relevance of differential inhibition of COX isozymes is as yet unknown . ^^^ As yet , no clinically available NSAID has been shown to have significant in vivo effects on COX 2 while sparing COX 1 activity in humans . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of COX 2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 mRNA was expressed in macrophages irrespective of OPZ stimulation , but COX 2 mRNA was expressed only after OPZ stimulation , and COX 2 protein was simultaneously induced . ^^^ Nimesulide affected neither the levels of COX 1 mRNA and COX 2 mRNA at 4 h after OPZ stimulation nor the levels of COX 2 protein at 10 h after OPZ stimulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , the relative contribution of cyclo oxygenase 1 ( COX 1 ) and COX 2 inhibition to this phenomenon was examined by use of whole cell patch clamp recordings in brain slices . ^^^ These findings suggest that COX 1 , rather than COX 2 inhibition , mediates the synergistic analgesic actions of opioids and non steroidal anti inflammatory drugs ( NSAIDs ) in the midbrain PAG . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By immunocytochemistry , COX 1 and COX 2 enzymes were localized to NSCLC tumors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of COX 1 and COX 2 inhibition on induction and maintenance of carrageenan evoked thermal hyperalgesia in rats . ^^^ Two isozymes of the COX enzyme have been reported , COX 1 and COX 2 , but the agents thus far examined are not isozyme selective . ^^^ This study demonstrates that at least spinal COX 2 , if not both COX 1 and COX 2 , are necessary for the initiation of thermal hyperalgesia , whereas nonspinal sources of prostanoids ( synthesized by COX 2 and perhaps also COX 1 ) are important for the maintenance of thermal hyperalgesia associated with tissue injury and inflammation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : Both isoforms of cyclo oxygenase , COX 1 and COX 2 , are inhibited to varying degrees by all of the available nonsteroidal anti inflammatory drugs ( NSAIDs ) . ^^^ Because inhibition of COX 1 by NSAIDs is linked to gastrointestinal ulcer formation , those drugs that selectively inhibit COX 2 may have less gastrointestinal toxicity . ^^^ We measured the extent to which NSAIDs and other anti inflammatory or analgesic drugs inhibit COX 1 and COX 2 in humans . ^^^ Blood was assayed for serum generated thromboxane B 2 synthesis ( COX 1 assay ) and for lipopolysaccharide stimulated prostaglandin E 2 synthesis ( COX 2 assay ) . ^^^ RESULTS : Inhibitory potency and selectivity of NSAIDs for COX 1 and COX 2 activity in blood varied greatly . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
VEGF ( 10 ng / ml ) induced constitutive COX 1 expression in both HUVEC and BAE , but not the cytokine inducible isoform , COX 2 , inducible NOS or endothelial NOS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NCX 4016 on COX 1 and COX 2 activity were compared , as was their analgesic activity . ^^^ Aspirin , but not NCX 4016 , markedly suppressed systemic COX 1 and COX 2 activity , and colonic prostaglandin synthesis . ^^^ This effect occurred independent of inhibition of COX 1 or COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 1 and COX 2 mRNA was detected by RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase regulates colon carcinoma induced angiogenesis by two mechanisms : COX 2 can modulate production of angiogenic factors by colon cancer cells , while COX 1 regulates angiogenesis in endothelial cells . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the effects of interleukin 1alpha ( IL 1alpha ) , tumor necrosis factor alpha ( TNF alpha ) , dexamethasone , and 17beta estradiol on the expression of cyclooxygenase 1 ( COX 1 ) and COX 2 in bovine chondrocytes . ^^^ METHODS : Northern blot analysis was used to quantify COX 1 and COX 2 mRNA expression in primary cultures of bovine chondrocytes and prostaglandin production to evaluate COX activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Analysis of fibroblast proteins showed the induction of cyclooxygenase 1 ( Cox 1 ) by TGF beta 1 and the induction of Cox 2 by IL 1 beta and TNF alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Many of aspirin ' s therapeutic effects arise from its acetylation of cyclooxygenase 2 ( COX 2 ) , whereas its antithrombotic and ulcerogenic effects result from its acetylation of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results demonstrate that dietary n 6 PUFAs upregulate COX 2 and , to some extent , COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of serum thromboxane ( TX ) B 2 and inflammatory exudate prostaglandin ( PG ) E 2 were used as indicators of the magnitude and time course of blockade of cyclo oxygenase isoforms COX 1 and COX 2 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Comparative molecular modeling study of the three dimensional structures of prostaglandin endoperoxide H 2 synthase 1 and 2 ( COX 1 and COX 2 ) . ^^^ The ovine COX 1 structure , solved by 10 ray diffraction methods and sharing a 61 % sequence identity with human COX 2 , was used as template . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Unlike COX 2 , levels of COX 1 mRNA were comparable in lupus patients and control subjects and were not influenced by the disease activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cultured EC and SMC demonstrate higher levels of both COX 1 and COX 2 with PCR analyses than do vascular wall biopsies from HUAB and HUVB . ^^^ This indicates a difference in the native expression of COX 1 and COX 2 in cultures of EC and SMC compared to that in biopsies from intact vessel walls . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 on carrageenan induced paw inflammation were assessed , along with extent of suppression of COX 1 and COX 2 . ^^^ The role of COX 1 in inflammation was also assessed in COX 2 deficient mice . ^^^ The degree of suppression of prostaglandin synthesis at the site of inflammation correlated significantly with inhibition of COX 1 but not COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , all prenyl hydroquinones inhibited the release of nitrite and PGE 2 in LPS stimulated J 774 cells , without direct effects on cyclo oxygenase 1 ( COX 1 ) , cyclo oxygenase 2 ( COX 2 ) or inducible nitric oxide synthase ( iNOS ) activities in several cell free systems . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , two isozymes of cyclooxygenase , COX 1 and COX 2 , which are key enzymes in prostaglandin ( PG ) biosynthesis , were identified and COX 2 was induced following the activation of cells by a variety of proinflammatory agents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclo oxygenase 1 ( COX 1 ) is believed to produce prostaglandins vital to mucosal defence , whereas cyclo oxygenase 2 ( COX 2 ) is induced at sites of inflammation . ^^^ In this study , we examined COX 1 and COX 2 expression shortly after administration of NSAIDs or ethanol . ^^^ Three hours later the stomach was excised , the severity of damage scored and samples taken for RT PCR of COX 1 and COX 2 mRNA and immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our results suggest that PGs mediating nociception in the formalin test of the rat are most likely produced via the COX 1 as well as COX 2 pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When exposed to lipopolysaccharide ( LPS ) , the induction of COX 2 and the enhancement of PGE 2 synthesis upon CaI were much lower in TGM as compared with RM the releasability of arachidonic acid upon CaI stimulation was relatively unchanged in RM but was reduced in TGM Thus , in TGM as compared with RM , a lower level of COX 1 expression and a lower level of COX 2 induction , and the reduction of arachidonate releasability by LPS exposure , are mainly responsible for lower PGE 2 synthetic ability upon CaI stimulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Phenylbutazone and FM have distinct effects on carrageenan induced cyclooxygenase ( COX 2 ) and platelet COX ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression and cellular localization of COX 1 and COX 2 in normal human colon and inflammatory bowel disease ( IBD ) surgical resections were studied . ^^^ METHODS : COX 1 and COX 2 protein expression and cellular localization were assessed by Western blotting and immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA expression and PGE 2 production were measured by Northern blot assay and enzyme linked immunosorbent assay , respectively . ^^^ RESULTS : LPS increased Mphi COX 2 mRNA expression but had no effect on COX 1 mRNA expression . ^^^ Inhibition of NFkappaB with TPCK reduced COX 2 but not COX 1 gene expression and decreased PGE 2 production by LPS stimulated Mphi . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cytosolic PLA 2 and COX ( the constitutive COX 1 and the inducible COX 2 ) was assessed by using immunohistochemical and quantitative immunoblotting procedures . ^^^ Cultured astrocytes and neurons expressed the three enzymes : cytosolic PLA 2 , COX 1 , and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms , COX 1 , a constitutive enzyme and COX 2 , the induced form , products of two different genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : These data demonstrate that the in vitro and in vivo pharmacological profile of meloxicam is structurally dependent and that minor structural changes can lead to significant differences in the selectivity for COX 1 and COX 2 in vitro and to different profiles in vivo suggesting different therapeutic potential . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase , the rate limiting enzyme in prostaglandin synthesis , occurs in two isoforms distinguished on the basis of constitutive ( COX 1 ) or inducible ( COX 2 ) expression patterns in mammalian tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study presents the development and validation of a new radioimmunoassay of 15 keto dihydro PGF2alpha as an index of lipid peroxidation via cyclooxygenase ( COX 1 and COX 2 ) pathway . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 mRNA was measured using a previously validated quantitative RT PCR assay . ^^^ RESULTS : COX 2 expression exceeded that of COX 1 by approximately eight fold . ^^^ COX 1 expression did not change but COX 2 expression was found to increase four fold with labour . ^^^ As in the amnion , it is COX 2 and not COX 1 which is upregulated with labour . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Caco 2 cells expressed very low levels of Cox 1 but highly expressed Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins are well characterised inflammatory mediators , whose formation is regulated by constitutive ( COX 1 ) or inducible ( COX 2 ) isoforms of cyclo oxygenase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The experiences with currently used NSAID , which show an increasing incidence of side effects as COX 1 inhibition increases , and studies with the COX 2 selective NSAID salsalate and meloxicam , which have less adverse effects than nonselective COX inhibitors in equivalent antiphlogistic dosage , prove the concept of selective COX 2 inhibition to avoid the NSAID typical side effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Detection of COX 1 and COX 2 isoforms in synovial fluid cells from inflammatory joint diseases . ^^^ OBJECTIVE : To investigate the expression of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in cells from synovial fluid ( SF ) of patients with acute or chronic arthritis . ^^^ COX 1 and COX 2 gene expression was studied by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ RESULTS : There was expression of COX 1 mRNA in all and COX 2 mRNA in most of the SF samples from acute or chronic arthritis . ^^^ By immunocytochemistry , both COX 1 and COX 2 immunoreactivity was restricted to a variable fraction of mononuclear cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent data demonstrate that there are 2 isoforms of the cyclo oxygenase enzyme , called COX 1 and COX 2 . ^^^ Normal physiologic functions appear to be maintained by COX 1 , while COX 2 appears to mediate the inflammatory response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study was undertaken to determine the effects of short term administration of LPS on gastric secretion and gastric damage induced by 100 % ethanol and to assess the role of the gene expression of two isoforms of cyclooxygenase ( COX ) , constitutive ( COX 1 ) and inducible ( COX 2 ) , and endogenous prostaglandins ( PG ) on these effects of LPS . ^^^ COX 2 mRNA was not detected in rats treated with ethanol but , when LPS was applied before ethanol , the enhanced expression of COX 2 was detected without affecting COX 1 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of a Th 1 cell associated cytokine ( interferon gamma [ IFN gamma ] ) and Th 2 cell associated cytokines ( interleukin [ IL ] 4 , IL 10 , and IL 13 ) on prostaglandin ( PG ) production by human alveolar macrophages ( AM ) were examined in terms of four parameters : PGE 2 synthesis , cyclooxygenase ( COX ) activity , and the protein and mRNA of two COX isozymes ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To estimate the importance of vasoactive prostaglandins and nitric oxide ( NO ) for HPV modification , we examined the roles of constitutive and inducible forms of cyclooxygenase ( COX 1 and COX 2 ) and those of NO synthase ( eNOS and iNOS ) . ^^^ Indomethacin was used for inhibiting both COX 1 and COX 2 , while NS 398 was used as a selective inhibitor of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : The effects of CDB were evaluated using the following assays : 1 ) acute inflammation induced by the injection of carrageenan , bradykinin and serotonin into the subplantar region of the hind paw of rats ; 2 ) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats ; 3 ) acute pain induced by the i . p . injection of phenyl p quinone into mice resulting in the production of writhes ; 4 ) cyclooxygenase ( COX ) activity , including COX 1 and COX 2 , evaluated using whole blood ; and 5 ) activity of peptidylglycine alpha monooxygenase ( PAM ) isolated from Xenopus laevis skin . ^^^ In addition , CDB significantly inhibited COX 1 activity ( IC 50 approximately = 17 microM ) while having only a weak inhibitory activity on both COX 2 and PAM activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The ratio of PGE 2 to PGD 2 produced by HUVECs was similar to that obtained by purified COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition to cyclooxygenase 1 ( COX 1 ) , COX 2 is also constitutively expressed in human HSC , and the use of dexamethasone and of SC 58125 , a selective COX 2 inhibitor , revealed that COX 2 accounts for basal COX activity . ^^^ Moreover , COX 2 mRNA and protein were up regulated by ET 1 and TNF alpha , whereas COX 1 was unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A comparison of the steady state levels of Cox1p through Cox4p in the COX 1 , COX 2 , COX 3 and COX 4 mutants shows the interdependance of the accumulation of these four subunits in the mitochondrial membranes . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A dose and time dependent increase in COX 2 mRNA and protein expression was evoked by IL 1beta , whereas the levels of COX 1 , the constitutively expressed isoform , remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results suggest that human ASM can be a source of IL 8 and also that endogenous prostanoids , involving both COX 1 and COX 2 , have a novel role in mediating BK induced IL 8 production . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gastric blood flow ( GBF ) was measured by H 2 gas clearance technique and gastric mucosal specimens were taken for the assessment of cell proliferation rate in gastric mucosa by bromodeoxyuridine ( BrdU ) uptake , mucosal generation of prostaglandin E 2 measured by radioimmunoassay , and for expression of SP , TGF alpha COX 1 and COX 2 mRNA as determined by RT PCR . ^^^ COX 1 expression was detected in vehicle control gastric mucosa and after single exposure to ASA or after six consecutive ASA insults , while COX 2 mRNA was not detected in vehicle control gastric mucosa , but appeared after single ASA insult and was sustained after subsequent ASA doses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By 6 h after hippocampal colchicine injection in rat , COX 2 ( but not COX 1 ) mRNA expression was elevated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Newborn pigs were treated intravenously every 8 hours for 48 hours with saline , 40 mg / kg nonselective COX inhibitor ibuprofen , 80 mg / kg COX 1 inhibitor valeryl salicylate , or 5 mg / kg DuP 697 and 5 mg / kg NS 398 , COX 2 inhibitors . ^^^ Retinal vessel EP 1 , EP 3 , and FP receptor densities increased approximately threefold after treatments with COX 1 or COX 2 inhibitors , and five to sixfold after ibuprofen treatment . ^^^ CONCLUSIONS : Data suggest that increased COX 1 and COX 2 catalyzed prostaglandin synthesis contribute equivalently to the downregulation of retinovascular EP 1 , EP 3 , and FP receptors and their vasoconstrictor functions in newborn pigs ; the EP 2 receptor was not significantly influenced by ontogenic alterations in prostaglandin levels . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Vitamin E supplementation completely reversed the increased COX activity in old mice to levels comparable to those of young mice but had no effect on macrophage COX activity of young mice or on COX 1 and COX 2 protein or COX 2 mRNA expression in young or old mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The conversion of arachidonic acid ( AA ) to prostaglandin H 2 is catalyzed at least by two isoforms of cyclooxygenase , named Cox 1 and Cox 2 . ^^^ Cox 1 is thought to be ubiquitously expressed , enrolled in physiological processes , whereas Cox 2 is mostly assumed to be dynamically regulated , responding to inflammatory conditions . ^^^ These data suggest a physiological role of Cox 2 rather than Cox 1 in the regulation of vascular tone in rat lungs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This isoprostane is also produced by the cyclooxygenase enzymes COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The isoform , which is constitutively expressed ( Cox 1 ) , and mediates physiological functions of prostaglandins , and the inducible isoform ( Cox 2 ) which is upregulated by inflammatory stimuli . ^^^ This study attempts to determine whether a Cox 2 selective inhibitor , flosulide , differs from the mixed type Cox 1 and Cox 2 inhibitor aspirin in respect of renal function and eicosanoid excretion in experimental nephritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , we assessed the effects of meloxicam , a selective inhibitor of COX 2 , and indomethacin , an unselective inhibitor of COX 1 and COX 2 , on furosemide stimulated plasma renin activity ( PRA ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase isoforms have been identified and are referred to as COX 1 and COX 2 . ^^^ Under many circumstances the COX 1 enzyme is produced constitutively ( i . e . , gastric mucosa ) whereas COX 2 is inducible ( i . e . , sites of inflammation ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
They support the concept that , in these cells , the COX 2 isoform is preeminent over COX 1 for the stimulated production of prostanoids , and also suggest that neutrophil COX 2 displays a distinct profile of expression among circulatory cells . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : The proportion of COX 2 to COX 1 expression was elevated in most human colorectal cancers and adenomas , but not in hyperplastic polyps . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Flavan 3 ols isolated from some medicinal plants inhibiting COX 1 and COX 2 catalysed prostaglandin biosynthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the efficacy and safety of SC 58635 ( celecoxib ) , an antiinflammatory and analgesic agent that acts by selective cyclooxygenase 2 ( COX 2 ) inhibition and is not expected to cause the typical gastrointestinal ( GI ) , renal , and platelet related side effects associated with inhibition of the COX 1 enzyme . ^^^ CONCLUSION : SC 58635 achieves analgesic and antiinflammatory efficacy in arthritis through selective COX 2 inhibition , without showing any evidence of 2 of the toxic effects of COX 1 inhibition associated with nonsteroidal antiinflammatory drugs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The former action was due to inhibition of COX 1 , while the latter effect was accounted for by inhibition of COX 2 and was mimicked by the COX 2 selective inhibitor NS 398 . ^^^ NO ASA , although it inhibited both COX 1 and COX 2 activity , had no deleterious effects on gastric ulcerogenic and healing responses . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) have been described : constitutive ( COX 1 ) and inducible ( COX 2 ) . ^^^ In normal kidney , cortical COX 1 IP was immunolocalized predominantly to mesangial cells and collecting tubules , whereas COX 2 IP was found in a subset of cortical thick ascending limb of Henle ' s loop ( CTAL ) cells in the region of the macula densa ( MD ) . ^^^ SC 58560 , a selective COX 1 inhibitor , did not inhibit PG production in the remnant glomeruli at concentrations up to 10 ( 4 ) M , whereas SC 58236 , a relatively selective COX 2 inhibitor , significantly inhibited PG production by RA glomeruli . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent studies have shown the existence of two isoforms of cyclooxygenase : COX 1 , now often referred to as the constitutive form , and COX 2 , an inducible form which is the major isoenzyme involved in prostaglandin synthesis in inflammation and other pathological situations . ^^^ In the present study , we evaluated the inhibitory properties of cyclooxygenase inhibitors on human COX 1 and COX 2 using a heterologous expression system . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) have been identified : a constitutive isoform ( COX 1 ) , found in abundance in platelets and the vascular endothelium , and an `` inflammatory ' ' cytokine inducible isoform ( COX 2 ) . ^^^ Untreated venous or arterial cells contained undetectable levels of COX 1 or COX 2 and released low levels of metabolites . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we examined the effects of cholecalciferol , a primary keratinocyte metabolite and precursor of the hydroxylated form of vitamin D 3 , 1alpha , 25 dihydroxyvitamin D 3 [ 1alpha , 25 ( OH ) 2D3 ] , on prostaglandin E 2 ( PGE 2 ) production in human keratinocytes by examining its respective effects on cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , and cytosolic phospholipase A 2 ( cPLA 2 ) expression , the rate limiting enzymes regulating PGE 2 biosynthesis and differentiation of keratinocytes . ^^^ Although cPLA 2 mRNA and protein were constitutively expressed in untreated HaCaT cells , expression levels did not increase in response to cholecalciferol treatment ; however , unlike COX 1 and cPLA 2 expression , COX 2 mRNA and COX 2 protein expression increased in response to cholecalciferol treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These findings demonstrate that 1 ) in normal bladders , the activation of B 1 and B 2 receptors evokes contraction that is largely mediated by COX 1 metabolites , whereas the COX 2 appears to be involved in PGE 2 production after the activation of B 1 receptor only , without interfering with contraction , and 2 ) in inflamed bladders , the activation of B 1 and B 2 receptors still produce PGE 2 , but the contractile response is not reduced by COX inhibitors , a result that indicates that additional mechanisms play a compensatory role . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vivo selectivity of nonsteroidal anti inflammatory drugs on COX 1 COX 2 and gastrointestinal ulcers , in rats ] . ^^^ This work was aimed to study COX 1 and COX 2 selectivity in 16 non steroidal anti inflammatory drugs ( NSAIDs ) , at ulcerogenic doses in 2 experimental models : 1 ) provided subcutaneously ( sc ) , after solid food ( SF ) , ( antrum ulcers and intestinal erosions ) ; and 2 ) orally ( O ) ( fundic and intestinal erosions ) . ^^^ CONCLUSIONS : COX 2 COX 1 selectivity was demonstrated `` in vivo ' ' in aceclofenac , meloxicam , nabumetone , nimesulide and paracetamol . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Roles of COX 1 and COX 2 in gastrointestinal pathophysiology . ^^^ In this review , COX 1 and COX 2 proteins have been shown to be homologous in protein structure and ability to synthesize PG , but they have been also shown to be induced differently . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RT PCR was done on total RNA for mRNA expression of the constitutive ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A Western analysis revealed COX 1 to be constitutively expressed , whereas COX 2 was hardly expressed until 30 min after the PQ injection in the peritoneal cells . ^^^ These data thus indicate that potent analgesic activity of mofezolac against the present model to be more closely related to its potent inhibitory activity against COX 1 but not against COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cox 1 , cox 2 and cox 3 genes were used to evaluate the feasibility and efficiency of this approach . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This triterpenoid showed a significant COX 2 inhibitory effect , directly on the enzyme activity , with an IC 50 value of 130 microM and a COX 2 / COX 1 selectivity ratio of 0 . 6 . ^^^ Furthermore , no significant inhibition on COX 2 or COX 1 was observed by the triterpenoid , 18beta glycyrrhetinic acid ( 3 ) . ^^^ The direct inhibitory effect of 1 and 2 on COX 2 catalyzed prostaglandin biosynthesis increased with preincubation , indicating a time dependent inhibition , while the effect on COX 1 was found to be independent of preincubation time . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The enzymes cyclooxygenase 1 and cyclooxygenase 2 ( COX 1 and COX 2 ) catalyze the conversion of arachidonic acid to prostaglandin ( PG ) H 2 , the precursor of PGs and thromboxane . ^^^ While there are abundant data indicating that the inducible isoform , COX 2 , is important in inflammation and pain , the constitutively expressed isoform , COX 1 , has also been suggested to play a role in inflammatory processes . ^^^ To address the latter question pharmacologically , we used a highly selective COX 1 inhibitor , SC 560 ( COX 1 IC 50 = 0 . 009 microM ; COX 2 IC 50 = 6 . 3 microM ) . ^^^ SC 560 inhibited COX 1 derived platelet thromboxane B 2 , gastric PGE 2 , and dermal PGE 2 production , indicating that it was orally active , but did not inhibit COX 2 derived PGs in the lipopolysaccharide induced rat air pouch . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists in 2 related but unique isoforms : one is constitutive ( COX 1 ) and functions in normal cell physiology , and the other is inducible ( COX 2 ) and is expressed in response to inflammatory stimuli . ^^^ In this study , we evaluated COX 1 and COX 2 expression in the kidneys of mixed breed dogs , Sprague Dawley rats , cynomolgus monkeys , and humans . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX enzyme family consists of the classical COX 1 enzyme , which is constitutively expressed in many tissues , and a second enzyme , i . e . , COX 2 , which is induced by various stimuli , such as mitogens and cytokines , and is involved in many inflammatory reactions . ^^^ Because nonsteroidal anti inflammatory drugs inhibit both COX 1 and COX 2 , these drugs also cause unwanted side effects , exemplified by gastrointestinal bleeding . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Treatment of rat serosal connective tissue mast cells ( CTMC ) with nerve growth factor ( NGF ) induced only the delayed phase of PGD 2 generation that depended on inducible cyclooxygenase 2 ( COX 2 ) , but not constitutive COX 1 , even though the subcellular distributions of these isoforms were similar . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 was examined with Western blot . ^^^ Protein levels of COX 2 , but not COX 1 , were substantially increased in amnion cells treated with HA fragment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
New NSAIDS : COX 1 , COX 2 , what about them ? ] . ^^^ Although such a mechanism was already described 25 years ago , the recent discovery of two isoforms of cyclooxygenase , the cyclooxygenase 1 ( COX 1 ) constitutively expressed in most tissues and the cyclooxygenase 2 ( COX 2 ) , inducible , has prompted research in developing new NSAID that would be safer whilst maintaining their efficacy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Serum thromboxane B 2 was determined as an index of Cox 1 activity and endotoxin induced prostaglandin E 2 formation in whole blood as an index of Cox 2 activity . ^^^ Nimesulide was highly selective against ovine Cox 2 , so that at concentrations attained in vivo , it had no effect on Cox 1 but completely suppressed Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX enzyme family consists of the classical COX 1 enzyme , which is constitutively expressed in many tissues , and a second isozyme , i . e . , COX 2 , which is induced by various stimuli , such as mitogens and cytokines , and is involved in many inflammatory reactions . ^^^ Because nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit both COX 1 and COX 2 , these drugs also cause unwanted side effects , exemplified by gastrointestinal bleeding . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since nimesulide is considered to be a selective inhibitor of COX 2 , it has not been studied in detail in relation to its mechanistic effects on platelets , which express COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MF Tricyclic was compared with the nonselective COX 1 / COX 2 inhibitor indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The efficacy of the sulfides in inhibiting COX 2 activity in inflammatory cells , our recent results on the selectivity of 70 in attenuating growth of COX 2 expressing colon cancer cells , and its selectivity for inhibition of COX 2 over COX 1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two Cox genes have been cloned ( Cox 1 and Cox 2 ) , of which Cox 2 has recently been found to be expressed in several human carcinomas . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , the benefit in UV protection of meloxicam as a preferential COX 2 antagonist was not above the reported benefit of the `` old ' ' COX 1 inhibiting NSAIDS . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : There are two isoforms of cyclo oxygenase ( COX ) , namely COX 1 and COX 2 . ^^^ METHODS : The expression of COX 1 and COX 2 isoenzymes has been studied in the bronchial mucosa of 10 normal and 18 asthmatic subjects , 11 of whom had aspirin sensitive asthma ( ASA ) and seven had non aspirin sensitive asthma ( NASA ) RESULTS : There was a significant fourfold and 14 fold increase , respectively , in the epithelial and submucosal cellular expression of COX 2 , but not of COX 1 , in asthmatic patients . ^^^ There was no significant difference in the total number of cells staining for either COX 1 or COX 2 between subjects with ASA and NASA , but the number and percentage of mast cells that expressed COX 2 was significantly increased sixfold and twofold , respectively , in individuals with ASA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
For instance , COX 2 ( and not COX 1 ) is thought to be involved in ovulation and in labor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , in situations where the release of protective PGs by COX 1 has been lost , the induction of COX 2 may compensate and reduce inflammatory responses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Despite variability among these systems , which precludes direct comparison of data , analysis of the ratio of inhibition of COX 1 to COX 2 by non steroidal anti inflammatory drugs , suggests inhibitors can be classified based on their COX selectivity . ^^^ Although in vitro systems are important for characterizing COX 1 and COX 2 inhibitory activity , the clinical relevance of these data should be considered carefully . ^^^ The level of inhibition of COX 1 and COX 2 , in vivo at a given dose in patients , can not be predicted from in vitro data alone . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The lowest COX 2 selectivities , which means the highest COX 1 selectivities , were observed in indomethacin , aspirin , and oxaprozin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis using isoform specific antibodies showed that the inducible cyclooxygenase enzyme ( COX 2 ) was expressed by 4 h in LPS and IL 1beta treated cells while the constitutive COX 1 remained unaltered in its expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition : current status and future perspective . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of Cox 1 and Cox 2 genes was quantified in the organum vasculosum lamina terminalis ( OVLT ) and choroid plexus ( CP ) in an attempt to determine whether altered expression of prostaglandin ( PG ) synthetic enzymes in brain vasculature is involved in LPS fever . ^^^ Although vascular endothelial cells in both structures expressed Cox 1 and Cox 2 mRNAs , neither increased in the OVLT following LPS . ^^^ However , in the CP , Cox 1 mRNA was enhanced ( p < 0 . 05 ) at 30 and 120 min after LPS injection and Cox 2 showed a similar ( NS ) change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Bioactivation of NNK was more extensive by COX 2 than COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of both enzymes occur : a constitutive one , Cox 1 and the inducible counterpart Cox 2 ; also NOS has a constitutive counterparts ( cNOS ) and an inducible form , called iNOS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is responsible for the production of physiological levels of prostanoids , whereas COX 2 is upregulated during inflammatory states and produces prostanoids responsible for the generation of fever , pain or other inflammatory responses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Three recent developments with respect to therapy with nonsteroidal anti inflammatory drugs ( NSAIDs ) are the identification of two isoenzymes of cyclooxygenase ( COX 1 and COX 2 ) , the development of NO NSAIDs , and the availability of low dose over the counter ( OTC ) NSAIDs . ^^^ COX 1 products mainly have a physiologically regulating and protective effect , while COX 2 products result in inflammation . ^^^ However , recent animal data indicate that high doses of COX 2 antagonists are usually necessary to obtain an adequate anti inflammatory effect , which doses also antagonize COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibitory activity and the mechanism of action of JTE 522 ( 4 ( 4 cyclohexyl 2 methyloxazol 5 yl ) 2 fluorobenzenesulfonamid e ) , a novel selective cyclooxygenase ( COX ) 2 inhibitor , on human COX 1 and COX 2 were investigated and compared with those of reference compounds . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis showed that this is due to greater COX 1 protein expression in newborn than in fetal vascular cells ; COX 2 protein expression was not detected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The PG synthase cyclooxygenase ( COX ) has two forms , COX 1 and COX 2 . ^^^ COX 2 , but not COX 1 , contributes to ulcer healing . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Efficacy with selective blockade of COX 2 may be inferior to that achieved with combined inhibition of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoenzymes : COX 1 , mostly involved in the production of prostaglandins that are important for the normal function of the organism , such as protection of the stomach , vascular homeostasis and kidney function , and COX 2 which is induced by proinflammatory stimuli and is mostly present in inflammatory cells . ^^^ Conceivably , the COX 1 and COX 2 functions are not separated very strictly . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In any case , specific COX 2 inhibitors are expected to show antiinflammatory and analgesic activities equivalent to those of NSAID , as well as significant reductions in the incidence of the life threatening side effects ( i . e . , GI bleeding ) associated with COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The non steroidal anti inflammatory drug ( NSAID ) indomethacin inhibits both constitutive and inducible forms of cyclo oxygenase ( COX 1 and COX 2 , respectively ) , while nimesulide is a selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclo oxygenase ( COX ) have been identified ; a constitutive isoform ( COX 1 ) , found in abundance in platelets and the vascular endothelium , considered important for the roles of prostanoids and a cytokine / mitogen inducible isoform ( COX 2 ) , which is thought responsible for the majority of the inflammatory prostanoid production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MATERIALS AND SUBJECTS : In vitro studies were performed using rat basophilic leukemia ( RBL 1 ) cells , human polymorphonuclear leukocytes ( PMNL ) , COX 1 from ram seminal vesicle , COX 2 from sheep placenta and human venous blood . ^^^ Influence on COX was determined in the perfused rabbit ear , in PMNL and in a test assay using COX 1 and COX 2 . 5 LOX activity was studied using PMNL and RBL 1 . ^^^ In the isolated enzyme preparations of COX 1 and COX 2 the IC 50 was 10 microM and 8 microM , that of indomethacin 9 . 2 mM and 2 . 4 microM . ^^^ CONCLUSIONS : MGL is a COX 1 , COX 2 and 5 LOX inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 and gastrointestinal diseases ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The protein level of COX 2 was examined in these cell lines by Western analysis , and mRNA levels of COX 1 / 2 by Northern analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A series of novel 2 pyridinyl 3 ( 4 methylsulfonyl ) phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase , COX 1 , and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We examined the effect of intrathecally administered NS 398 , a selective COX 2 inhibitor and indomethacin , an non selective COX 1 and COX 2 inhibitor , on the development of thermal hyperalgesia induced by the activation of NMDA or AMPA receptors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The activity of COX 1 was not inhibited by TJ 14 even at a dose of 1000 microg / ml , while COX 2 was inhibited at dose levels between 10 and 1000 microg / ml . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A reverse transcriptase polymerase chain reaction study detected the expression of COX 1 and COX 2 mRNA in intact rat epididymis and in cultured epididymal epithelia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Analysis of COX 1 and COX 2 protein levels in HCA 7 tumor lysates revealed a slight decrease in COX 2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is a constitutive enzyme , generally involved in cell functions , while COX 2 is commonly an enzyme which is inducible in response to various stimuli , including mitogens . ^^^ Recently , specific inhibitors of COX 1 and COX 2 enzymes have been developed . ^^^ PURPOSE : The present study was undertaken to determine the effects of specific COX 1 and COX 2 inhibitors on the proliferation and the induction of apoptosis of intestinal epithelial cells . ^^^ The effects of serum on proliferation were then evaluated in the presence of the COX 1 inhibitor , valerylsalicyclic acid ( VSA ) , the COX 2 inhibitor , SC 58125 , or indomethacin . ^^^ The presence of COX 1 and COX 2 protein was evaluated by Western blotting . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSION : These data imply a regulatory role for COX 2 but not COX 1 in the spinal modulation under acute and chronic peripheral inflammation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed enhanced expression of the COX 2 protein in some tumors as compared with normal esophageal squamous epithelium , whereas similar amounts of the COX 1 protein were found in normal and cancerous tissues . ^^^ OSC 2 cells expressed COX 2 but not COX 1 , whereas OSC 1 cells expressed high levels of COX 1 but showed only a very weak COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Specific NF kappaB blockade selectively inhibits tumour necrosis factor alpha induced COX 2 but not constitutive COX 1 gene expression in HT 29 cells . ^^^ While COX 1 is mostly constitutively expressed , the COX 2 isoform is inducible by proinflammatory cytokines . ^^^ We conclude that NF kappaB activation is critical in mediating COX 2 , but not COX 1 gene expression in HT 29 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Experiments on cells transfected with either COX alone revealed subtle differences between the PG biosynthetic properties of the two isozymes in that COX 1 and COX 2 were favored over the other in the presence of high and low exogenous AA concentrations , respectively . ^^^ Moreover , COX 2 , but not COX 1 , could turn on endogenous AA release , which was inhibited by a cPLA 2 inhibitor . ^^^ When PLA 2 and COX were coexpressed , AA released by cPLA 2 , sPLA 2 IIA and sPLA 2 5 was converted to PGE 2 by both COX 1 and COX 2 during the immediate response and predominantly by COX 2 during the delayed response . ^^^ Ca2+ independent PLA 2 ( iPLA 2 ) ( type 6 ) , which plays a crucial role in phospholipid remodeling , failed to couple with COX 2 during the delayed response , whereas it was linked to ionophore induced immediate PGE 2 generation via COX 1 in marked preference to COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) mRNA were measured by ribonuclease protection assays in total RNA extracted from intercaruncular and caruncular endometrium , myometrium , cotyledons , and cervical mucosa of pregnant cows . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In AD brains , protein levels of COX 1 were increased in both cytosolic and particulate fractions , and COX 2 protein was also increased in the particulate fraction . ^^^ Thus , expression levels of COX 1 , COX 2 , and PPARgamma may change in AD brains . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 ( COX 2 ) more selectively than cyclooxygenase 1 ( COX 1 ) . ^^^ Molecular modelling studies have been carried out on complexes of 1 with COX 1 and with mutants of COX 1 simulating COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of Cox 2 was also elevated in most tumors , whereas Cox 1 was frequently expressed at lower levels in the tumor tissue than in the paired normal tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , which catalyzes the conversion of arachidonic acid to prostanoids exists in two isoforms , COX 1 and COX 2 . ^^^ The purpose of this study was to determine the relative contributions of COX 1 and COX 2 in the production of prostanoids by human intestinal smooth muscle ( HISM ) cells when stimulated by interleukin 1beta ( IL 1beta ) and lipopolysaccharide ( LPS ) . ^^^ Furthermore the effects of specific COX 1 and COX 2 inhibitors on the proliferation of smooth muscle cells was also evaluated . ^^^ Unstimulated and stimulated cells were exposed to the specific COX 1 inhibitor valerylsalicylic acid ( VSA ) and the COX 2 inhibitors NS 398 and SC 58125 . ^^^ Immunoblot analysis using isoform specific antibodies showed that both COX 1 and COX 2 were present constitutively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exposure of EC to cyclic strain induced promoter activity and expression of COX 2 but not of COX 1 . ^^^ These results demonstrate that , unlike shear stress , cyclic strain does not affect COX 1 expression and is a weak inducer of COX 2 promoter activity in bovine aortic EC with minimal effect on mRNA expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We measured protein levels of CO subunits encoded by mitochondrial ( COX 1 , COX 2 ) and nuclear ( COX 4 , COX VIc ) DNA in autopsied brain of patients with AD whom we previously reported had decreased cerebral cortical CO activity . ^^^ In the spinocerebellar ataxia disorders , COX 1 and COX 2 levels were significantly decreased in cerebellar cortex ( 22 to 32 % ) but were normal or close to normal in cerebral cortex , an area relatively unaffected by neurodegeneration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Rats were treated with the COX 1 / COX 2 inhibitor indomethacin and the selective COX 2 inhibitors meloxicam and SC 58125 . ^^^ The data suggest that COX 1 and COX 2 products mediate these effects differently because the selective COX 2 inhibitors had less influence on chemokine expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) the rate limiting enzyme in PG biosynthesis has two isoforms , the constitutive COX 1 and an inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The non specific cyclooxygenase ( COX ) inhibitor , indomethacin , the selective COX 1 inhibitors , resveratrol and valerylsalicylate , and the specific COX 2 inhibitors , NS 398 , etolodac and DFU ( 5 , 5 dimethyl 3 ( 3 fluorophenyl ) 4 ( 4 methylsulphonyl ) phenyl 2 ( 5H ) furanone ) all caused a significant dose dependent inhibition of the biosynthesis of PGE immunoreactive material . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The stimulation of intestinal epithelial cell cyclooxygenase ( COX ) enzymes with inflammatory agents and the inhibition of COX 1 and COX 2 enzymes has the potential to increase understanding of the role of these enzymes in intestinal inflammation . ^^^ Valerylsalicylic acid ( VSA ) was employed as the COX 1 inhibitor , and SC 58125 and NS 398 were used as the COX 2 inhibitors . ^^^ Western immunoblotting demonstrated the presence of constitutive COX 1 and inducible COX 2 enzyme . ^^^ Ca Ion stimulated prostanoid formation was uniformly inhibited by COX 2 , but not COX 1 , inhibitors . ^^^ IL 1 beta stimulated PGE 2 and PGE 2 alpha formation was significantly decreased by both COX 1 and COX 2 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists in two isoforms , COX 1 and COX 2 , COX 1 is present and is constitutively expressed in most cells and tissues , whereas COX 2 is felt to principally mediate inflammation . ^^^ This review addresses the roles of COX 1 and COX 2 isoforms in physiologic and pathophysiologic states and reviews potential therapeutic roles for selective COX inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the role of two isoforms , COX 1 and COX 2 , in the development and metastasis of gastric carcinoma . ^^^ COX 1 and COX 2 protein expression were evaluated using Western blotting analysis , and their relative band densities were semi quantified using standard densitometry scanning techniques . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It was found that immunoreactive COX 2 protein levels were approximately 3x higher than COX 1 levels in NMU induced mammary tumors . ^^^ Moreover , the high menhaden oil diet ( rich in n 3 fatty acids ) significantly suppressed both COX 1 ( 28 % ) and COX 2 ( 36 % ) protein levels when compared to the high corn oil diet . ^^^ The mechanism ( s ) by which n 3 fatty acids suppress COX 1 and COX 2 remain to be determined . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme have been identified : COX 1 and COX 2 . ^^^ Recent studies have suggested that COX 2 , but not COX 1 , may play a role in colorectal tumorigenesis . ^^^ In the present study , we investigated the expression of COX 2 as well as COX 1 in human hepatocellular carcinoma ( HCC ) tissues using immunohistochemistry and immunoblotting . ^^^ The expression of COX 1 was weaker than that of COX 2 in hepatic neoplastic and non neoplastic parenchymal cells . ^^^ Immunoblotting also confirmed up regulation of COX 2 , but not COX 1 , in well differentiated HCCs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of the present study was to investigate the involvement of cyclooxygease 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in prostaglandin ( PG ) production by human periodontal ligament ( PDL ) fibroblasts stimulated with a proinflammatory cytokine , inerleukin 1beta ( IL 1beta ) , and to examine the effect of interleukin 4 ( IL 4 ) , a Th 2 cytokine , and interferon gamma ( IFN gamma ) , a Th 1 cytokine , on PG production by the cells . ^^^ Indomethacin , a non selective COX 1 / COX 2 inhibitor , and NS 398 , a selective COX 2 inhibitor , completely inhibited PGE 2 production by IL 1beta stimulated cells . ^^^ Northern blot analysis showed that COX 2 mRNA was detected in IL 1beta stimulated PDL cells , although not detected in unstimulated cells , while expression of COX 1 mRNA was in the same extent in both the cells . ^^^ Northern blot analysis showed that IL 4 depressed COX 2 mRNA expression with no effect on COX 1 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The former action is due to inhibition of COX 1 , while the latter effect may be accounted for by inhibition of COX 2 and mimicked by NS 398 , the COX 2 selective NSAID . ^^^ NCX 4016 , despite inhibiting both COX 1 and COX 2 , protects the stomach against damage and preserves the healing response of gastric ulcers , probably because of the beneficial action of NO . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We hypothesized that COX 2 inhibitors may not affect the ductus if the predominant COX isoform is COX 1 . ^^^ In contrast to our hypothesis , fetal lamb ductus arteriosus expressed both COX 1 and COX 2 immunoreactive protein ( by Western analysis ) . ^^^ Although COX 1 was found in both endothelial and smooth muscle cells , COX 2 was found only in the endothelial cells lining the ductus lumen ( by immunohistochemistry ) . ^^^ The relative contribution of COX 1 and COX 2 to PGE 2 synthesis was consistent with the immunohistochemical results : in the intact ductus , PGE 2 formation was catalyzed by both COX 1 and COX 2 in equivalent proportions ; in the endothelium denuded ductus , COX 2 no longer played a significant role in PGE 2 synthesis . ^^^ NS 398 , a selective inhibitor of COX 2 , was 66 % as effective as the selective COX 1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Moreover , relative to COX 1 or COX 2 , diclofenac induced enzyme activity shows significantly reduced sensitivity to inhibition by diclofenac or other competitively acting nonsteroid antiinflammatory drugs ( NSAIDs ) and the enzyme activity is insensitive to aspirin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 : functions and pharmacological effects ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of the cyclooxygenase COX 1 and COX 2 were found . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The author gives a brood outline of the circumstances of the inhibition of cyclooxygenase ( COX ) giving special emphasis to the different role of the two isoforms COX 1 and COX 2 . ^^^ To set a correct determination of COX 2 / COX 1 quotiens is difficult because of numerous methodical problems . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Implantation and decidualization are defective in cyclooxygenase 2 ( Cox 2 ) , but not Cox 1 , deficient mice . ^^^ We therefore used Northern and in situ hybridization to investigate changes in uterine expression of Cox 1 and Cox 2 genes during various stages of pregnancy in the spotted skunk . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have shown the HUVEC from normal pregnancy contained COX 1 protein but not COX 2 protein and released 6 keto PGF 1 alpha 277 + / 5 ng / ml ( for 24 h ) . ^^^ In contrast , HUVEC from preeclampsia contained both COX 1 and COX 2 protein and released significantly lesser amounts of 6 keto PGF 1 alpha ( 159 + / 8 ng / ml for 24 h ; p < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , two forms of cyclooxygenase have been found to exist : COX 1 and COX 2 , the constitutive and inducible forms , respectively . ^^^ COX 1 exists in the stomach , intestine , kidneys and platelets , while COX 2 , the inducible form , is expressed during inflammation . ^^^ The therapeutic effects of NSAIDs are largely the result of inhibition of the enzyme cyclooxygenase 2 ( COX 2 ) , whereas the toxic effects ( e . g . , gastrointestinal , renal and platelet effects ) are primarily due to the inhibition of COX 1 . ^^^ Individual NSAIDs show different potencies against COX 1 compared with COX 2 and this explains the variations in the side effects of NSAIDs at their anti inflammatory doses . ^^^ Drugs with high potency against COX 2 and a better COX 2 / COX 1 activity ratio will have anti inflammatory activity with fewer gastrointestinal side effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Comparative computer modeling of the 10 ray crystal structures of cyclooxygenase isoforms COX 1 and COX 2 has led to the design of COX 2 selectivity into the nonselective inhibitor flurbiprofen . ^^^ The COX 2 modeling was based on a postulated binding mode for flurbiprofen and took advantage of a small alcove in the COX 2 active site created by different positions of the Leu 384 sidechain between COX 1 and COX 2 . ^^^ The design hypothesis was tested by synthesis and biological assay of a series of flurbiprofen analogs , culminating in the discovery of several inhibitors having up to 78 fold selectivity for COX 2 over COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 : so what . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Nonsteroidal anti inflammatory drugs ( NSAIDs ) such as aspirin , ibuprofen , and indomethacin ( INN , indometacin ) inhibit both the constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms of cyclooxygenase . ^^^ Single oral doses of rofecoxib and indomethacin were then assessed in subjects with use of ex vivo COX isoform specific assays ( serum thromboxane B 2 [ TXB 2 ] and lipopolysaccharide [ LPS ] stimulated whole blood prostaglandin E 2 and assays of COX 1 and COX 2 activity , respectively ) . ^^^ RESULTS : Rofecoxib showed a > 800 fold COX 2 selectivity with use of CHO cells that express human COX 1 and COX 2 . ^^^ All active treatments showed greater improvement than placebo ( P < . 001 ) CONCLUSIONS : Rofecoxib inhibited COX 2 without evidence of COX 1 inhibition , even at oral doses of up to 1000 mg . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Neither hyperglycemia nor diabetes altered COX 1 expression , but embryonic COX 2 expression was diminished on gestational day 10 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the activity of carprofen and other nonsteroidal anti inflammatory drugs ( NSAID ) against isozymes of canine cyclooxygenases ( COX 1 and COX 2 ) . ^^^ PROCEDURE : Constitutive COX 1 was obtained from washed canine platelets , and COX 2 was obtained from a canine macrophage like cell line that was induced with endotoxin . ^^^ Activity of carprofen and other NSAID against COX 1 and COX 2 was compared . ^^^ Ratio of the COX 1 to COX 2 IC50 was used as a measure of isozyme selectivity . ^^^ Potency of carprofen for canine COX 2 was more than 100 fold greater than for canine COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive astroglial COX 1 or COX 2 did not play any role in purine induced reactive astrogliosis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LC at higher concentrations ( 6 . 8 10 10 ( 5 ) M ) and INDO 10 ( 6 ) M inhibited PGE 2 formed by COX 2 and also partly by COX 1 activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclo oxygenase , constitutive ( COX 1 ) and inducible ( COX 2 ) enzyme , have been reported . ^^^ In the present study , we have immunohistochemically mapped the distribution of both COX 1 and COX 2 during various physiological states of the rat uterus . ^^^ Observation of the stained sections under the light microscope revealed that , in non pregnant rat uterus , both COX 1 and COX 2 were abundantly expressed in the endometrium , with minimal staining observed in the myometrium . ^^^ In pregnant rats , although the expression of both COX 1 and COX 2 was localized primarily to the endometrium with very little staining in the myometrium on day 1 of gestation , both of these enzymes were also apparent in myometrial cells by day 4 of gestation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The benefits derived from NSAIDs are believed to be due to suppression of cyclooxygenase 2 ( COX 2 ) , while the harmful side effects are believed to be due to suppression of cyclooxygenase 1 ( COX 1 ) . ^^^ COX 2 specific inhibitors that do not inhibit COX 1 may meet arthritis sufferers ' needs for therapies that are safe , convenient , and as effective as conventional NSAIDs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Unlike conventional nonsteroidal anti inflammatory drugs , which inhibit both forms of the COX enzyme , celecoxib inhibits COX 2 preferentially to COX 1 in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This is possible because celecoxib is a cyclooxygenase 2 ( COX 2 ) specific inhibiting agent that inhibits the conversion of arachidonic acid to the prostaglandins that mediate pain and inflammation while having no effect on the formation of the prostaglandins that mediate normal homeostasis in the gastrointestinal tract , kidneys , and platelets and that are formed under the control of cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme , cyclo oxygenase ( COX 1 and COX 2 ) , in human fetal membranes throughout pregnancy , at mRNA , protein and activity levels . ^^^ Protein concentrations of COX 1 did not change , whilst concentrations of COX 2 increased from the first to the third trimester . ^^^ These data suggest that it is up regulation of COX 2 , rather than of COX 1 , which mediates increased prostaglandin synthesis within the fetal membranes at term . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of the cyclooxygenase ( COX ) enzyme have been identified : COX 1 , which is expressed constitutively , and COX 2 , which is induced in inflammation . ^^^ It had IC 50 values of 0 . 14 and 100 microM against recombinant human COX 2 and purified ovine COX 1 , respectively . ^^^ It inhibited COX 2 activity in the J774A . 1 cell line with an IC 50 of 0 . 18 microM and inhibited COX 1 activity in platelets with an IC 50 of 3 . 1 microM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The selectivity for COX 2 over COX 1 is dramatically improved by substituting the 2 phenyl group with halogens in the meta position or by replacing the phenyl ring with a 2 or 3 pyridyl ring . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While both co cultured EC and SMC expressed cyclooxygenase ( Cox 1 and Cox 2 ) , they were differentially regulated by pulsatile flow , EC Cox 1 and Cox 2 protein expression were both decreased . ^^^ Indomethacin treatment increased the expression of both Cox 1 and Cox 2 in co cultured SMC under high flow conditions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of the present study was to investigate the involvement of cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , and tyrosine kinase on prostaglandin E 2 ( PGE 2 ) production in human gingival fibroblasts stimulated by interleukin 1beta ( IL 1beta ) and / or epidermal growth factor ( EGF ) . ^^^ The tyrosine kinase inhibitors , Herbimycin A and PD 153035 hydrochloride , reduced COX 2 mRNA levels as well as PGE 2 production induced by IL 1beta or the combination of IL 1beta and EGF whereas COX 1 mRNA levels were not affected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The predominant isozyme expressed in cortical thymic epithelial cells was COX 1 , while COX 2 predominated in the medulla . ^^^ Selective inhibition of COX 2 , but not COX 1 , blocked the adhesion of CD4+CD8+ and CD4+CD8 thymocytes to medullary cell lines . ^^^ These data further support the differential regulation of COX 1 and COX 2 expression and function in thymic stromal cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of leukocyte infiltration was observed with indomethacin and nimesulide , but only at doses that inhibited both COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Also , COX 2 , not COX 1 , was found to mediate delayed PGE 2 production because the response was completely blocked by the specific COX 2 inhibitor NS 398 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Half maximal inhibition ( IC 50 ) using end point assays reflects the competitive component on COX 1 ( IC50=4 19 microM ) and the inactivation component on COX 2 ( IC50=0 . 003 0 . 006 microM ) . ^^^ Although IC 50 determinations are useful for structure / activity analyses , the complex and distinct mechanisms of enzyme inhibition of each COX isoform by the NSAIDs renders comparison of inhibitory activity on COX 1 and COX 2 using IC 50 ratios of questionable validity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Conventional nonsteroidal anti inflammatory drugs inhibit both cyclooxygenase ( Cox ) isoforms ( Cox 1 and Cox 2 ) and may be associated with nephrotoxicity . ^^^ Healthy older adults ( n = 36 ) were admitted to a clinical research unit , placed on a fixed sodium intake , and randomized under double blind conditions to receive the specific Cox 2 inhibitor , MK 966 ( 50 mg every day ) , a nonspecific Cox 1 / Cox 2 inhibitor , indomethacin ( 50 mg t . i . d . ) , or placebo for 2 weeks . ^^^ Our data suggest that acute sodium retention by nonsteroidal anti inflammatory drugs in healthy elderly subjects is mediated by the inhibition of Cox 2 , whereas depression of GFR is due to inhibition of Cox 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OAS 1000 was therefore evaluated as an inhibitor of 4 enzymes of the arachidonic acid metabolic pathways ( prostaglandin G / H synthase 1 ( PGHS 1 , COX 1 ) , prostaglandin G / H synthase 2 ( PGHS 2 , COX 2 ) , arachidonate 5 lipoxygenase ( 5 LOX ) , and arachidonate 15 lipoxygenase ( 15 LOX ) ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) , the enzyme that catalyzes the conversion of arachidonic acid to prostanoids , are now recognized : a constitutively expressed COX 1 and a highly regulated COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As a result of research into the differences between COX 1 and COX 2 , new insights into the role of each isoform in normal homeostasis and in their responses to exogenous stimuli have emerged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we assessed the febrile response to LPS of congenitally constitutive COX 1 ( COX 1 / ) and COX 2 ( COX 2 / ) deficient C57BL / 6J derived mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of cyclooxygenase ( COX ) , COX 1 and COX 2 . ^^^ A human colon carcinoma cell line , COLO 320DM , was transfected with an eukaryotic expression vector carrying cDNA of either COX 1 or COX 2 , the expression of which was driven by a powerful elongation factor 1alpha promoter in pEF BOS . ^^^ Both COX 1 and COX 2 expressing cells possessed a similar enzyme activity , 8 10 nmol / 10 min per mg protein . ^^^ Although COX 1 and COX 2 are believed to have fundamentally different biological roles , essentially no differences in growth stimulation were observed between the COX 1 and COX 2 overexpressions in our experiments . ^^^ A COX inhibitor , indomethacin , suppressed the stimulated growth , increased DNA synthesis and induction of epidermal growth factor receptor in COX 1 and COX 2 transfected cells . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In unstimulated airway smooth muscle cells , COX 1 , but not COX 2 protein was detectable by Western blotting . ^^^ The induction of COX 2 protein by the cytokine mixture was attenuated by dexamethasone ( 100 nM ) , whereas the level of COX 1 protein was unaffected by either the cytokines or by dexamethasone . 8 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The desired effects of NSAIDs are related to inhibition of COX 2 , whereas inhibition of COX 1 has been linked to the typical side effects of NSAIDs , especially in the stomach and kidney . ^^^ The great differences between effects and side effects in the numerous substances can be explained because of different interactions of the NSAIDs on COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent research has shown that COX exists as at least two isoenzymes , COX 1 and COX 2 . ^^^ Compelling evidence suggests that COX 1 synthesizes prostaglandins that are involved in the regulation of normal cell activity ( including G 1 cytoprotection ) , whereas COX 2 appears to produce prostaglandins mainly at sites of inflammation . ^^^ These findings led to the search for compounds that would inhibit COX 2 without affecting COX 1 . ^^^ These preliminary trials show that celecoxib achieves analgesic and antiinflammatory efficacy in arthritis through specific COX 2 inhibition without showing evidence of two of the toxic effects of COX 1 inhibition associated with NSAID . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here , we have analyzed the localization of COX 1 and COX 2 in rat experimental autoimmune encephalomyelitis ( EAE ) , C 6 glioblastoma and 9L gliosarcoma by immunohistochemistry . ^^^ Double labeling experiments confirmed expression of COX 2 in vWF+ ( endothelial ) cells and COX 1 in ED1+ ( macophages ) , OX6+ ( MHC class 2 ) and in W3 / 13+ ( lymphoblasts ) cells . ^^^ These data provide further evidence that expression of COX 1 in macrophages / microglial cells and COX 2 in endothelial cells might represent important regulatory mechanisms in inflammatory processes associated with autoimmunity and neoplasia of the rat brain . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In mammals , the increased generation of prostaglandins ( PG ) during the onset of inflammatory responses and activation of immune cell types has been attributed to the induction of a novel cyclo oxygenase ( COX ) isoform , termed COX 2 , which is distinct from the well characterized constitutive activity ( COX 1 ) . ^^^ The predicted translation product had high homology to known mammalian and chicken COX 2 ( 83 84 % ) and COX 1 ( 77 % ) sequences . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : Cyclooxygenase , either the cox 1 or cox 2 isoform , controls synthesis of prostaglandin E 2 ( PGE 2 ) , which regulates expression of matrix metalloprotease 9 ( MMP 9 ) . ^^^ In situ , hybridization for cox 1 and cox 2 showed that cox 2 , but not cox 1 , was expressed and was co localized by immunohistochemistry to macrophages associated with the aortic wall . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin synthesis is catalyzed by cyclooxygenase ( COX ; prostaglandin synthase ) which occurs as two isozymes , COX 1 and COX 2 . ^^^ COX 1 and COX 2 are constitutively expressed in brain whereas COX 2 type is also inducible in brain by excitatory neurotransmission . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is expressed physiologically while inducible COX 2 is expressed in pathological situations . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AA also provides a substrate for cyclooxygenase ( COX ) , resulting in PGE 2 production . 1 , 25 mediates its effects through COX 1 , the constitutive enzyme , but not COX 2 , the inducible enzyme . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A series of novel sulfone substituted 4 , 5 diarylthiazoles have been synthesized and evaluated for their inhibition of the two isoforms of human cyclooxygenase ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent information indicates that prostanoids are produced by two cyclooxygenase ( COX ) enzymes , COX 1 and COX 2 . ^^^ Unstimulated and stimulated cells were exposed to specific COX 1 and COX 2 inhibitors . ^^^ In freshly isolated normal gallbladder mucosal cells , continuously produced 6 keto PGF1alpha was inhibited by both COX 1 and COX 2 inhibitors while PGE 2 levels were not affected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 1 is diffusely expressed in lymphoid cells in embryonic day 15 . 5 thymus , COX 2 expression is sparse , apparently limited to stromal cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
GB tissue from control and BDL groups was examined for COX 1 , COX 2 , PS , and inducible nitric oxide synthase ( iNOS ) content by Western blot analysis , analyzed by densitometry , and reported as densitometry units . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The antiinflammatory action of aspirin generally has been attributed to direct inhibition of cyclooxygenases ( COX 1 and COX 2 ) , but additional mechanisms are likely at work . ^^^ Here , we show that the antiinflammatory effects of aspirin and sodium salicylate , but not glucocorticoids , are largely mediated by the antiinflammatory autacoid adenosine independently of inhibition of prostaglandin synthesis by COX 1 or COX 2 or of the presence of p 105 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the extent of human cyclooxygenase 1 ( COX 1 ) inhibition by meloxicam , which has been reported to preferentially inhibit cyclooxygenase 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , the uterine expression of COX 1 and COX 2 throughout the menstrual cycle [ late follicular , day 5 postovulation ( PO ) , day 10 PO , and day 14 PO ] and pregnancy ( days 12 18 , day 39 , day 51 , and near term ) was analyzed using semiquantitative RT PCR , in situ hybridization , and immunocytochemistry . ^^^ Treatment of animals with the antiprogestin ( ZK 137 . 316 ) for 9 days ( beginning on the day of the LH surge ) inhibited COX 1 expression in the epithelium when the tissue was analyzed on day 10 PO , whereas COX 2 expression disappeared in the epithelium and increased in the stroma . ^^^ Finally , near term decidua expressed very little COX 1 or COX 2 mRNA . ^^^ These studies suggest that in the baboon endometrium , COX 1 expression is regulated primarily by progesterone , whereas regulation of COX 2 expression may involve additional mediators of embryonic origin at the site of implantation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mice deficient in COX 1 are fertile but have decreased pup viability , whereas mice deficient in COX 2 fail to ovulate and have abnormal implantation and decidualization responses . ^^^ In both COX 1 and COX 2 deficient mice , pituitary gonadotropins were selectively increased , whereas hypothalamic LHRH and serum gonadotropin levels were similar to those in wild type animals ( + / + ) . ^^^ Wild type and COX 1 ( / ) mice ovulated in response to PMSG / hCG ; very few COX 2 ( / ) animals responded to this regimen . ^^^ Collectively , these data demonstrate that COX 2 , but not COX 1 , is required for the gonadotropin induction of ovarian PG levels ; that COX 2 related prostanoids are required for stabilization of the cumulus oophorum during ovulation ; and that ovulation can be restored in the COX 2 ( / ) animals by simultaneous treatment with gonadotropins and PGE 2 or interleukin 1beta . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Infected mice had increased phospholipase A 2 mRNA expression in the spleen and cyclooxygenase 1 ( COX 1 ) and COX 2 expression in the brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The preliminary in vivo experience with COX 2 selective inhibitors has provided evidence for proof of concept for the COX 1 and COX 2 hypothesis , namely that the selective inhibition of COX 2 derived prostaglandins is sufficient to inhibit inflammation and is nonulcerogenic . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast to L 1 preadipocytes , adipocytes and rat liver , RT PCR and Western analyses did not detect COX 1 or COX 2 expression in cultured primary hepatocytes . ^^^ Taken together , these studies show that COX 1 and COX 2 do not contribute to the n 6 PUFA suppression of hepatocyte lipogenic gene expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All 3 corticosteroids markedly reduced COX 2 with little effect on COX 1 , cPLA 2 ( Type 4 ) , or iPLA 2 ( Type 6 ) immunoreactivity or their relative distribution in cytosol versus membrane fractions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed , whereas COX 2 is induced by proinflammatory stimuli . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found both COX 1 and COX 2 to be constitutively expressed in all organs tested , i . e . , brain , heart , liver , kidney , spleen and intestine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Replacement of valine with isoleucine at this position provides access to a binding site that is larger in COX 2 than in COX 1 . ^^^ We made these conclusions from a three dimensional molecular model of the active site of human COX 2 , constructed using the 10 ray coordinates of COX 1 from sheep seminal vesicles and COX 2 from mouse fibroblasts as templates , with the aid of sequence alignment methods and molecular modelling techniques . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Antipromotion activity was indicated by antiinflammatory effects , inhibition of production of arachidonic acid metabolites catalyzed by either COX 1 or COX 2 , and chemical carcinogen induced neoplastic transformation of mouse embryo fibroblasts . ^^^ As judged by the reverse transcriptase polymerase chain reaction , resveratrol selectively inhibited TPA induced expression of c fos and transforming growth factor beta 1 ( TGF beta 1 ) , but did not affect other TPA induced gene products including COX 1 , COX 2 , c myc , c jun , and tumor necrosis factor alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Generally , COX 1 is constitutively expressed in most tissues , where it maintains physiological processes ; inducible COX 2 is considered a pro inflammatory enzyme and a chief target for the treatment of inflammatory diseases . ^^^ The selective COX 2 inhibitor NS 398 and the dual COX 1 / COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Blood samples were taken before and up to 6 h after dosing and the plasma obtained from it was tested for its ability to inhibit prostanoid formation in IL 1beta treated A 549 cells ( COX 2 system ) and human washed platelets ( COX 1 system ) . ^^^ All drugs , except sodium salicylate , inhibited COX 1 and COX 2 when added directly to the test systems . ^^^ Plasma from aspirin treated rats was without effect on either COX 1 or COX 2 , consistent with the rapid in vivo metabolism to salicylate . ^^^ Conversely , plasma from sulindac treated rats inhibited COX 1 and COX 2 with potencies according with in vivo metabolism to sulindac sulphide . ^^^ Diclofenac was COX 1 / 2 non selective when tested in vitro , but a slightly preferential inhibitor of COX 2 when tested ex vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These comparisons of the actions of > 40 NSAIDs and novel COX 2 selective agents , including celecoxib , rofecoxib and diisopropyl fluorophosphate , demonstrate a distribution of compound selectivities toward COX 1 that aligns with the risk of serious gastrointestinal complications . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of antiinflammatory drugs on COX 1 and COX 2 activity in human articular chondrocytes . ^^^ OBJECTIVE : To study the effect of steroidal and nonsteroidal antiinflammatory drugs ( NSAID ) on cyclooxygenase ( COX 1 and COX 2 ) activity in human articular chondrocytes . ^^^ Unstimulated and interleukin 1 ( IL 1 ) stimulated chondrocytes were used as models to study the effects of drugs on COX 1 and COX 2 . ^^^ Indomethacin and diclofenac were the most potent inhibitors of COX 1 ( IC 50 = 0 . 063 microM and 0 . 611 microM , respectively ) and COX 2 isoforms ( IC 50 = 0 . 48 microM and IC 50 = 0 . 63 microM , respectively ) . ^^^ Among all drugs tested dexamethasone showed the greatest selectivity for COX 2 and meloxicam was the NSAID with the best COX 2 / COX 1 ratio ( r = 0 . 12 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TPA treatment also elevates the expression of cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , c myc , c fos , c jun , transforming growth factor beta 1 ( TGF beta 1 ) and tumor necrosis factor alpha ( TNF alpha ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Concentration response curves for the inhibition of monocyte COX 2 and platelet COX 1 were obtained in vitro after the incubation of meloxicam with whole blood samples . ^^^ In contrast , the administration of 7 . 5 and 15 mg of meloxicam caused dose dependent reductions in monocyte COX 2 activity by 51 % and 70 % , respectively , and in platelet COX 1 activity by 25 % and 35 % , respectively . ^^^ Although the IC 50 value of meloxicam for inhibition of COX 1 was 10 fold higher than the IC 50 value of COX 2 in vitro , this biochemical selectivity was inadequate to clearly separate the effects of meloxicam on the two isozymes after oral dosing as a function of the daily dose and interindividual variation in steady state plasma levels . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Compared with currently available NSAIDs ( which inhibit COX 1 and COX 2 isoforms of cyclooxygenase ) , MK 0966 ( a specific COX 2 inhibitor ) is expected to cause less gastrointestinal toxicity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclo oxygenase ( COX ) exists as two isoforms , COX 1 , the constitutive isoform , and COX 2 , which is inducible by cytokines or inflammatory stimuli and may participate in airway inflammation . ^^^ METHODS : We measured COX 1 and COX 2 in cultured human airway smooth muscle ( HASM ) cells , MRC 5 fibroblasts and normal human epithelial cells ( NHBE ) using immunocytochemical analysis . ^^^ CONCLUSION : COX 1 is expressed constitutively in human airway fibroblasts , smooth muscle and epithelial cells but epithelial cells also show constitutive expression of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , known to exist in two isoforms , COX 1 and COX 2 , is a key enzyme in prostaglandin synthesis and the target for most nonsteroidal anti inflammatory drugs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Moreover , side effects and adverse events may be significantly reduced through the use of COX 2 specific inhibitors , new agents that alleviate pain and inflammation without the liability for adverse events caused by COX 1 inhibition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonetheless , in the clinical setting of reduced renal perfusion as seen in various forms of cardio renal disease , dehydration , and the aging kidney , the adequacy of renal prostaglandin production mediated predominantly by cyclooxygenase 1 ( COX 1 ) and , potentially , by COX 2 enzyme activity becomes of major significance in the activation of compensatory renal hemodynamics . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , it has been found that there are two closely related forms of COX , which are now known as COX 1 and COX 2 . ^^^ The basis for these important differences lies in the genes for COX 1 and COX 2 and the regulation of these genes . ^^^ All conventional nonsteroidal anti inflammatory drugs ( NSAIDs ) nonspecifically inhibit both COX 1 and COX 2 at standard anti inflammatory doses . ^^^ The beneficial anti inflammatory and analgesic effects occur through the inhibition of COX 2 , but the gastrointestinal toxicities and the mild bleeding diathesis occur as a result of concurrent inhibition of COX 1 . ^^^ Agents that would inhibit COX 2 while sparing COX 1 represent an attractive therapeutic development and could represent a major advance in the treatment of rheumatoid arthritis and osteoarthritis , as well as a diverse array of other conditions . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , these drugs inhibit both cyclooxygenase 1 ( COX 1 ) , which is essential for the regulation of homeostasis in many tissues , as well as COX 2 , which is an important mediator of pain and inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) may be present in cells in both constitutive ( COX 1 ) and inducible ( COX 2 ) forms . ^^^ After total mRNA extraction , COX 1 and COX 2 mRNA expression were measured using a reverse transcriptase ( RT ) semiquantitative PCR technique . ^^^ Hybrid primers of COX 1 . glyceraldehyde 3 phosphate dehydrogenase ( GAPDH ) or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists as constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms . ^^^ Nonsteroidal antiinflammatory drugs ( NSAIDs ) such as ibuprofen and diclofenac inhibit both COX 1 and COX 2 . ^^^ Specific inhibition of COX 2 by rofecoxib results in antipyretic activity in monkeys and humans comparable to dual COX 1 / COX 2 inhibitors such as diclofenac or ibuprofen . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists as two isoforms : COX 1 , which is constitutively expressed in most cell types , and COX 2 , which is inducible by LPS and cytokines in a variety of cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Structure activity relationship studies have demonstrated that central pyridine ring substituents play an important role in the COX 2 potency , selectivity vs the COX 1 enzyme , and oral activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Levels of both Cox 2 and constitutive cyclooxygenase ( Cox 1 ) were assessed using Western blot analysis . ^^^ Prior incubation of macrophages with ox LDL resulted in a strong inhibition of Cox 2 induced by LPS , without effect on Cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast to arylacetic acid NSAIDs , the alpha methylacetic acid sodium salt of 8a , or the methyl alpha methylacetate ester ( 7a ) did not inhibit cyclooxygenase 1 ( COX 1 ) or 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 2 mRNA level in aged cells was higher than that in young cells , whereas COX 1 mRNA remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
STUDY DESIGN : Molecular biological analysis of COX 1 and COX 2 in laryngeal papilloma . ^^^ Normal buccal mucosa biopsies showed low density or nondetectable autoradiographic signal for both COX 1 and COX 2 mRNAs . ^^^ Immunohistochemical staining for COX 1 and COX 2 showed a similar pattern to that seen with in situ hybridization in both normal and papilloma tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We determined COX 1 and COX 2 expression , and the corresponding PGE 2 secretions , in 4 ER negative human breast cancer cell lines , the MCF10A breast epithelial cell line , and the same non cancerous line transfected with a mutated ras gene . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study represents the first to examine the levels of mRNA expression of CYP 19 , COX 1 , and COX 2 genes in human breast cancer specimens and normal breast tissue samples using semi quantitative RT PCR methods . ^^^ Linear regression analysis using a bivariate model shows a strong linear association between CYP 19 expression and the sum of COX 1 and COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the key enzyme in PG biosynthesis , exists in two isoforms , COX 1 and COX 2 . ^^^ Western blot analyses showed that the newborn ( 4 day old ) brain expressed lower levels of COX 1 ( 8 fold ) , COX 2 ( 20 fold ) , bNOS ( 12 fold ) , and ecNOS ( 5 fold ) than in the 1 day old . ^^^ MV showed approximately equal levels of COX 2 , lower levels of COX 1 ( 4 fold ) , bNOS ( 5 fold ) , and higher levels of ecNOS ( 20 fold ) in comparison to 4 day old cerebral MV . ^^^ Purified MV showed lower ecNOS ( 14 fold ) , COX 1 ( 2 fold ) , and about equal levels of bNOS and COX 2 in comparison with MV from 6 week old pigs . ^^^ Treatment with noo nitro L arginine ( LNA ) , a NOS inhibitor , downregulated COX 1 expression in the newborn brain and both COX 1 and COX 2 cerebral MV expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA and protein levels were determined by RT PCR or Western blotting in Sprague Dawley rats on varying water intakes , in Brattleboro rats and in Long Evans controls . ^^^ We conclude that in inner medulla , COX 2 but not COX 1 is upregulated by hyperosmolality . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 compensation in the uterus of COX 1 deficient mice during the pre implantation period . ^^^ The two isoforms of cyclooxygenase , COX 1 and COX 2 , have distinct expression patterns in the mouse uterus during the peri implantation period and suggest their independent contribution to uterine PGs . ^^^ Most importantly , COX 1 ( / ) uteri displayed COX 2 expression on the morning of day 4 , when COX 2 is normally absent . ^^^ These data indicate that COX 1 derived PGs are important during uterine preparation for implantation , and that COX 2 compensation occurs in the absence of COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discoveries that cyclooxygenase ( COX ) 2 is an inducible form of COX involved in inflammation and that COX 1 is the major isoform responsible for the production of prostaglandins ( PGs ) in the gastrointestinal tract have provided a rationale for the development of specific COX 2 inhibitors as a new class of anti inflammatory agents with improved gastrointestinal tolerability . ^^^ Rofecoxib is a potent inhibitor of the COX 2 dependent production of PGE ( 2 ) in human osteosarcoma cells ( IC ( 50 ) = 26 + / 10 nM ) and Chinese hamster ovary cells expressing human COX 2 ( IC ( 50 ) = 18 + / 7 nM ) with a 1000 fold selectivity for the inhibition of COX 2 compared with the inhibition of COX 1 activity ( IC ( 50 ) > 50 microM in U 937 cells and IC ( 50 ) > 15 microM in Chinese hamster ovary cells expressing human COX 1 ) . ^^^ Rofecoxib is a time dependent inhibitor of purified human recombinant COX 2 ( IC ( 50 ) = 0 . 34 microM ) but caused inhibition of purified human COX 1 in a non time dependent manner that could only be observed at a very low substrate concentration ( IC ( 50 ) = 26 microM at 0 . 1 microM arachidonic acid concentration ) . ^^^ In an in vitro human whole blood assay , rofecoxib selectively inhibited lipopolysaccharide induced , COX 2 derived PGE ( 2 ) synthesis with an IC ( 50 ) value of 0 . 53 + / 0 . 02 microM compared with an IC ( 50 ) value of 18 . 8 + / 0 . 9 microM for the inhibition of COX 1 derived thromboxane B ( 2 ) synthesis after blood coagulation . ^^^ Using the ratio of the COX 1 IC ( 50 ) values over the COX 2 IC ( 50 ) values in the human whole blood assay , selectivity ratios for the inhibition of COX 2 of 36 , 6 . 6 , 2 , 3 , and 0 . 4 were obtained for rofecoxib , celecoxib , meloxicam , diclofenac , and indomethacin , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of COX , called COX 1 and COX 2 has led to further research into dissociating NSAID efficacy and intolerance . ^^^ COX 1 AND COX 2 : It appears that the antiinflammatory and antalgesic effects of NSAID is related to COX 2 inhibition while the undesirable effects on the gastric mucosa would be related to COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that , in the hepatoma cell lines , CCL13 / Chang and HepG 2 , indomethacin , a selective cyclo oxygenase 1 and 2 ( COX 1 and COX 2 ) inhibitor , increases IFN alpha stimulation of interferon stimulated response element ( ISRE ) dependent transcription in a dose dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several currently available nonsteroidal anti inflammatory drugs ( NSAIDs ) have been evaluated for their relative selectivity in inhibiting the two cyclooxygenase ( COX ) isozymes , COX 1 and COX 2 . ^^^ Rankings of the COX 2 / COX 1 inhibition ratios of various NSAIDs as they relate to the agents ' toxicities have been used as evidence that COX 2 selectivity is an important factor in the upper gastrointestinal ( GI ) safety of some NSAIDs . ^^^ What is needed are specific COX 2 inhibitors that do not inhibit COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent research has shown that COX exists as at least two isoenzymes , COX 1 and COX 2 . ^^^ Compelling evidence suggests that COX 1 synthesizes prostaglandins that are involved in the regulation of normal cell activity ( including GI cytoprotection ) , whereas COX 2 appears to produce prostaglandins mainly at sites of inflammation . ^^^ These findings led to the search for compounds that would inhibit COX 2 without affecting COX 1 . ^^^ These preliminary trials show that celecoxib achieves analgesic and anti inflammatory efficacy in arthritis through specific COX 2 inhibition without showing evidence of two of the toxic effects of COX 1 inhibition associated with NSAIDs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX 1 and COX 2 inhibitors in nerve injured rats . ^^^ In order to investigate the role of cyclooxygenase ( COX ) isozymes , relatively selective COX 1 ( piroxicam ) and COX 2 N [ 2 cyclohexyloxy 4 nitrophenyl ] metanesulfonamide ( NS 398 ) inhibitors were administered i . th . ( 60 microg ) alone or together with i . th . morphine . ^^^ These findings suggest that spinal prostanoids produced via both COX 1 and COX 2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX inhibitor combination therapy . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The constitutive enzyme COX 1 is found in most tissues and is believed to confer gastric mucosal protective action , and COX 2 , the inducible enzyme , is implicated in pain and inflammation . ^^^ Selective inhibition of COX 1 and COX 2 may allow prediction of drugs ' major effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The neuroprotective potency of NSAIDs appeared to be unrelated to their selective ability to inhibit cyclooxygenase 1 ( COX 1 ) or cyclooxygenase 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effects of nimesulide and indometacin on COX 1 and COX 2 : a comparative study . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Arachidonic acid oxygenation by COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to investigate whether COX 2 contributes to portal hypertension and whether a COX 2 blockade induces the same sort of gastric mucosal injury as a COX 1 blockade . ^^^ The mean arterial pressure ( MAP ) , portal pressure ( PP ) , visceral blood flow volume ( BFV ) , serum levels of 6 keto prostaglandin F1alpha ( PGF1alpha ) , thromboxane B 2 ( TXB 2 ) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors ( indomethacin , a highly selective COX 1 inhibitor ; NS 398 , a highly selective COX 2 inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
ET 3 ( 100 nM ) caused transient increases in the expression of both COX 2 mRNA and protein , but not those of COX 1 , in cultured astrocytes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we use primary embryonic fibroblasts derived from cyclooxygenase deficient transgenic embryos to further investigate the role of the two cyclooxygenases , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) , in the process of neoplastic transformation . ^^^ Our results show that when a cyclooxygenase enzyme is present , the transformed cells have marked increases in COX 2 and / or COX 1 expression . ^^^ Different nonsteroidal antiinflammatory drugs ( NSAIDs ) were used to examine their possible antineoplastic effects on the transformed cells , which have various levels of expression of COX 1 or COX 2 . ^^^ Our findings with cyclooxygenase knockout cells confirm recent reports that some of the antiproliferative and antineoplastic effects of NSAIDs are independent of the inhibition of either COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate anti inflammatory effects of lornoxicam in vitro on COX 1 / COX 2 , on NO formation from iNOS and on the formation of the pro inflammatory cytokines TNF alpha , IL 1beta , IL 6 , and IL 8 . ^^^ In whole blood inhibition of COX 1 was performed by measuring TXB 2 formation after clotting , and COX 2 inhibition was examined in LPS stimulated whole blood cultures . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA expressions were determined by Northern blot assays with mouse specific cDNA probes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In a human whole blood assay , measuring the accumulation of TxB 2 in response to calcium ionophore as a measure of COX 1 activity and in response to incubation with bacterial endotoxin as a measure of COX 2 activity , leflunomide inhibited COX 1 and COX 2 with IC 50 values of 31 and 185 microg ml 1 ; for A 771726 the corresponding values were 40 and 69 microg ml 1 . 6 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At the same time , COX inhibitors were tested to identify COX 1 and COX 2 activity . ^^^ In contrast , in the cell free homogenate of cultured human mast cells , EPA inhibited both COX 1 and COX 2 activities . ^^^ These findings suggest that COX 1 and COX 2 have different substrate flow systems in mast cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to examine the expression of the two isoforms of the central prostaglandin synthetic enzyme , cyclo oxygenase ( COX 1 and COX 2 ) in human myometrium throughout pregnancy and to test the hypothesis that COX in the myometrium may play a role in labour onset . ^^^ Expression of COX 1 and COX 2 at the mRNA level was analysed using reverse transcriptase polymerase chain reaction ( RT PCR ) and at the protein level using Western blotting . ^^^ These data would suggest that up regulation of COX 2 , rather than COX 1 , mediates increased prostaglandin synthesis in human myometrium at term . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin synthesising enzyme cyclooxygenase ( cox ) exists in two forms , one constitutive ( cox 1 ) and the other inducible ( cox 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 appears to regulate many normal physiologic functions , and COX 2 mediates the inflammatory response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , a non selective COX 1 / COX 2 inhibitor , and NS 398 , a selective COX 2 inhibitor , completely inhibited PGE 2 production by the IL 1alpha stimulated cells . ^^^ Expression of COX 2 protein in IL 1alpha stimulated cells was increased , compared with that in unstimulated cells , whereas COX 1 protein expression was almost the same in both the cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CMT 3 and 8 inhibit the sp . act . of COX 2 ( but not COX 1 ) in cell free extracts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The second approach is based on the discovery of two isoforms ( COX 1 and COX 2 ) of the cyclo oxygenase enzyme . ^^^ It was hypothesized that the constitutively expressed COX 1 isoenzyme leads to the synthesis of prostaglandins with homeostatic functions whereas COX 2 is merely responsible for the production of prostaglandins mediating pain , fever and inflammation . ^^^ There is some evidence that both COX 1 and COX 2 isoforms are involved in the production of prostaglandins associated with inflammation and homeostatic functions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 , COX 2 , and inducible nitric oxide synthase protein in human gastric antrum with Helicobacter pylori infection . ^^^ These findings were paralleled by marked increases in iNOS and in COX 1 and COX 2 protein expression . ^^^ However , the expression of COX 1 and COX 2 and the parallel increase of prostaglandin E 2 could imply that these factors could limit the extend of mucosal damage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 is constitutively expressed in a wide range of tissues , COX 2 is cytokine inducible . ^^^ Although COX 1 expression is observed in normal tissue , enhanced COX 2 expression has been attributed a key role in the development of edema , impeding blood flow and immunomodulation observed in pathologically altered tissues . ^^^ Here , we have analyzed the expression of COX 1 and COX 2 in 50 gliomas and 10 control brains with no neuropathological alterations by immunohistochemistry ; 22 glioblastoma multiforme , 9 anaplastic astrocytomas , 5 protoplasmic astrocytomas , 1 gemistocytic astrocytoma and 13 fibrillary astrocytomas were included in the study . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro enzyme assays indicated that despite its high potency in inhibiting growth and inducing apoptosis , CP 248 , like exisulind , lacked cyclooxygenase ( COX 1 and COX 2 ) inhibitory activity even at concentrations up to 10 mM . ^^^ Moreover , despite variations of COX 1 and COX 2 expression , the three benign and malignant prostate cell lines showed similar sensitivity to growth inhibition and induction of apoptosis by these three compounds . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We examined effects of I / R on expression of COX 1 and COX 2 isoforms in large cerebral arteries of anesthetized piglets . ^^^ Tissues were analyzed for COX 1 and COX 2 mRNA and protein using RNase protection assay and immunoblot analysis , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot and nuclease protection demonstrate that cultured MICs constitutively express COX 2 , with little constitutive COX 1 expression . ^^^ SC 58236 , a COX 2 selective inhibitor , but not SC 58560 , a COX 1 inhibitor , preferentially blocks PGE 2 synthesis in MICs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Accumulation of COX 2 , but not COX 1 , mRNA increased when cells were challenged with TNF ( 1 nM ) or PMA ( 1 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 protein expression was detected by the Western blot assay in three of five pancreatic carcinoma cell lines ( BxPC 3 , Capan 1 , and MDAPanc 3 ) , whereas COX 1 protein was detected in two of the five cell lines ( BxPC 3 and Capan 1 ) . ^^^ No correlation was found between the level of COX 2 or COX 1 expression and the extent of growth inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These observations suggest that , in the COX protein , a structural association of COX 2 with COX 1 is necessary to stabilize the binding of heme a 3 to COX I . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inhibition of either or both COX isoforms ( COX 1 and COX 2 ) . ^^^ METHODS : COX 1 and COX 2 expression by HuGE cells was investigated by western blot analysis , indirect immunofluorescence , reverse transcriptase polymerase chain reaction , and measurement of prostaglandin E ( 2 ) synthesis . ^^^ RESULTS : Under normal culture conditions ( 30 % serum ) , HuGE cells expressed COX 1 and low levels of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The development of cyclooxygenase ( COX ) deficient mice has allowed investigation into the individual physiological roles of the COX 1 and COX 2 isoforms . ^^^ In the following article , the phenotypes of the two Ptgs ( genes coding for COX 1 and COX 2 ) knockouts are summarized , and recent studies to investigate the effects of COX deficiency on cancer susceptibility , inflammatory response , gastric ulceration , and female reproductive processes are discussed . ^^^ However , for the maintenance of normal physiology , it appears that deficiency of COX 2 has more profound effects than deficiency of COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Some compounds showed strong ( 0 . 3 nM ) inhibitory activity on COX 2 and were found somewhat selective ( up to 16 ) on COX 2 over COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 is involved in physiologic maintenance , COX 2 seems to be involved in inflammation , mitogenesis , and specialized signal transductions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These compounds are a new class of drugs that specifically inhibit the enzyme COX 2 while having no effect on COX 1 across the whole therapeutic dose range . ^^^ The objectives of the meeting were to review the currently available data regarding the roles and biology of COX 1 and COX 2 , and to foster a consensus definition on COX 2 specificity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two COX isoforms , constitutive COX 1 and inducible COX 2 , has led to the hypothesis that selective inhibition of COX 2 will minimize the potential for GI toxicity without compromising efficacy . ^^^ These results may provide support for the hypothesis that selective inhibition of COX 2 relative to COX 1 might be an effective approach towards improved NSAID therapy . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of this study is to examine the expression of the key enzymes in prostaglandin synthesis : cyclooxygenase 1 ( COX 1 , constitutive ) and cyclooxygenase 2 ( COX 2 , inducible ) , during phagocytosis of ROS by RPE cells . ^^^ COX 1 and COX 2 mRNA expression was studied by quantitative competitive reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ During phagocytosis of ROS by RPE cells , RT PCR revealed an increase in mRNA expression of COX 2 , but not of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX ) is the rate limiting enzyme in the synthesis of PGs and exists in two isoforms , COX 1 and COX 2 . ^^^ In the present study , the expression of COX 1 and COX 2 was studied during the implantation period in healthy fertile women before and after treatment with the antiprogesterone , mifepristone . ^^^ Using polyclonal antibodies against COX 1 and COX 2 , immunostaining for COX 1 was found mainly in the glandular and luminal epithelium and for COX 2 mainly in the luminal epithelium and the perivascular cells . ^^^ After treatment with mifepristone , expression of COX 1 in glandular epithelium and COX 2 in luminal epithelium significantly decreased whilst the immunostaining for COX 2 in the perivascular cells remained strong . ^^^ This study shows the expression of both COX 1 and COX 2 during the implantation period and also indicates that treatment with mifepristone in early luteal phase impairs glandular epithelial function and endometrial receptivity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunohistochemistry was performed to localize these cytokines , cyclooxygenase ( COX ) 1 , COX 2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription polymerase chain reaction ( RT PCR ) to identify COX 1 and COX 2 expression . ^^^ Inflammatory mediators were localized to cervical tissue and COX 1 and COX 2 expression was confirmed by RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent discovery of the cyclooxygenase ( COX ) isoenzymes COX 1 and COX 2 has improved our knowledge of the action of NSAIDs . ^^^ COX 1 is continuously expressed in almost all tissues , where it converts arachidonate to the prostaglandins ( PGs ) important in homeostatic function ; COX 2 is present in immune cells , blood vessel endothelial cells , and synovial fibroblasts . ^^^ In theory , a drug such as celecoxib that selectively inhibited COX 2 might block inflammation , pain , and fever while reducing the side effects ( gastric erosions and ulcers ) associated with inhibition of COX 1 . ^^^ In animal models of inflammation and pain , celecoxib has shown marked suppression of PG production and inflammation compared with indomethacin , the standard COX 1 / COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( Cox 1 ) and Cox 2 convert arachidonic acid to prostaglandin H ( 2 ) , the precursor of other prostaglandins and thromboxanes , eicosanoids important in vascular pathophysiology . ^^^ Cox 1 mRNA and protein localized on endothelial and medial smooth muscle cells of normal arteries ( n = 5 ) , whereas Cox 2 expression was not detectable . ^^^ In contrast , atheromatous ( n = 7 ) lesions contained both Cox 1 and Cox 2 , colocalizing mainly with macrophages of the shoulder region and lipid core periphery , whereas smooth muscle cells showed lower levels , as demonstrated by immunohistochemical and in situ hybridization analysis . ^^^ In accord with immunohistochemical studies , Western blot analysis of protein extracts from normal arteries revealed constitutive Cox 1 , but not Cox 2 , expression . ^^^ Extracts of atheromatous lesions , however , contained both Cox 1 and Cox 2 protein , detected as two immunoreactive proteins of approximately 70 and 50 kd . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Thirty four cases of primary NSCLC were examined for both constitutive ( COX 1 ) and inducible COX ( COX 2 ) by means of in situ hybridization and immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase , a key enzyme in eicosanoid synthesis , has recently been shown to exist in two isoforms : the constitutive COX 1 and the inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dexamethasone ( 2 micromol / L ) , which also inhibited the HDL induced PGI ( 2 ) release , reduced significantly both Cox 2 mRNA and protein levels without affecting cPLA ( 2 ) and Cox 1 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , 2 isoforms of the enzyme responsible for prostaglandin synthesis , cyclooxygenase , have been described as cyclooxygenase 1 ( COX 1 ) , a constitutive isoform , and cyclooxygenase 2 ( COX 2 ) , an inducible isoform . ^^^ We inhibited prostaglandin synthesis by COX 1 and COX 2 with indomethacin ( 3 mg / kg ) and prostaglandin synthesis by COX 2 with NS 398 ( 3 mg / kg ) and tested the effect of these inhibitors on the renal functional changes elicited by renal ablation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new non steroidal anti inflammatory drug , that possesses a selective inhibition of the inducible isoform of cyclooxygenase enzyme ( COX 2 ) relative to the constitutive one , COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , a 1 h incubation with IL 1beta markedly increased the inducible COX 2 mRNA level , which was inhibited by an IL 1r antagonist and dexamethasone , whereas IL 1beta showed no effect on the level of constitutive COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isozymes of cyclooxygenase ( COX 1 and COX 2 ) . ^^^ Nonsteroidal anti inflammatory drugs currently used inhibit both COX 1 and COX 2 more or less , and causes gastric erosion and ulceration by inhibiting local production of prostaglandin E 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By immunohistochemistry , both COX 1 and COX 2 were localized to intercalated cells of the CCD on paraffin embedded mouse kidney sections . ^^^ When COX enzyme activity was measured in the M 1 cells , both indomethacin ( COX 1 and 2 inhibitor ) and the specific COX 2 inhibitor NS 398 effectively blocked PGE 2 synthesis . ^^^ These studies have for the first time localized COX 2 to the CCD and provided evidence that the intercalated cells of the CCD express both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pretreatment with 6 MNA , 30 microM , a COX 2 inhibitor with some activity on COX 1 , diclofenac , 1 microM ( COX 1 and 2 ) , or 1 ( 7 carboxyheptyl ) imidazole , 10 microM [ thromboxane ( TX ) synthase inhibitor ] but not indomethacin , 10 microM ( COX 1 inhibitor ) preserved the vasodilation induced by 5 HT after ischemia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Genetic evidence for distinct roles of COX 1 and COX 2 in the immediate and delayed phases of prostaglandin synthesis in mast cells . ^^^ Activation of mast cells from COX 2 ( / ) mice stimulates the release of PGD ( 2 ) during the first 30 min , whereas activation of mast cells from COX 1 ( / ) mice does not generate any PGD ( 2 ) in the first 2 h . ^^^ On the other hand , COX 2 ( / ) cells do not participate in delayed phase of PGD ( 2 ) synthesis , while COX 1 ( / ) cells secrete low levels of PGD ( 2 ) between 2 and 4 h after activation . ^^^ These data demonstrate that ( 1 ) the first phase of PG synthesis is COX 1 dependent and ( 2 ) the second , delayed phase of PG synthesis is dependent on activation induced synthesis and activity of COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study confirms that COX 2 derived prostanoids are important clinical mediators of pain and other symptoms of knee OA and that inhibition of COX 1 is not required to provide clinical benefit . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Biphenotypic B / macrophage cells express COX 1 and up regulate COX 2 expression and prostaglandin E ( 2 ) production in response to pro inflammatory signals . ^^^ A potential role for B / macrophage cells in inflammation was shown by their ability to express prostaglandin H synthase 1 ( COX 1 ) and prostaglandin H synthase 2 ( COX 2 ) and by their production of prostaglandin ( PG ) E ( 2 ) . ^^^ COX 1 and COX 2 mRNA expression is not observed in the precursor B lymphocytes and is not known to be a property of B lineage cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We describe that Cox 1 and Cox 2 are synthesized in rat pancreatic acinar cells . ^^^ Upon induction of pancreatitis , Cox 2 mRNA increases while Cox 1 expression remains constant . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although much effort has recently been focused on the inducible COX 2 isoform , little is known about COX 1 expression in human brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 protein , but not COX 1 protein , was induced in HUVEC from women with a normal pregnancy ( nHUVEC ) treated with serum from patients with preeclampsia ( pSerum ) , but not with serum from women with a normal pregnancy ( nSerum ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Rat hepatocytes and CC 1 cells , a rat hepatocyte cell line , displayed COX 1 but not COX 2 mRNA expression and predominantly produced thromboxane A ( 2 ) ( TXA ( 2 ) ) and 15 hydroxyeicosatetraenoic acid ( 15 HETE ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Increased COX 2 , but not COX 1 , mRNA expression in Helicobacter pylori gastritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study tested the hypothesis that the natriuretic response to increased RIHP during direct renal interstitial volume expansion is dependent on COX 1 but not COX 2 . ^^^ RIHP and fractional excretion of sodium ( FE ( Na ) ) were measured before and after direct renal interstitial volume expansion in control rats ( n=7 ) , rats infused with the COX 1 inhibitor piroxicam ( n=6 , 1 . 5 mg / kg ) , and rats infused with the COX 2 inhibitors NS 398 ( n=5 , 1 . 5 mg / kg ) and meloxicam ( n=6 , 0 . 3 mg / kg ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western immunoblot analysis showed that the observed effect of silymarin on COX activity was due to inhibition of TPA inducible COX 2 with no change in constitutive COX 1 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX exist : COX 1 represents the constitutively expressed enzyme , whereas COX 2 is the inducible isoform . ^^^ High dose flosulide treatment reduced renal prostaglandin production and caused a marked decline in COX 1 and COX 2 protein expression . ^^^ COX 1 and COX 2 protein expression was affected by high dose flosulide , which therefore might lose its selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The hypothesis that the gastrointestinal side effects of NSAIDs result from inhibition of COX 1 , but not COX 2 ( ref . 11 ) , prompted the development of NSAIDs that selectively inhibit only COX 2 ( such as celecoxib and rofecoxib ) . ^^^ Finally , we show that both COX 1 and COX 2 are important for the regulation of angiogenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoenzymes of COX have been identified , COX 1 and COX 2 . ^^^ The purpose of this study was to characterize COX 1 and COX 2 expression in human invasive transitional cell carcinoma of the urinary bladder by immunohistochemistry and Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Modulation of gastric levels of COX 1 and COX 2 mRNA by 1 R was evaluated using Northern blot and reverse transcription polymerase chain reaction . 2 . 1 R induced gastric damage was dose dependently aggravated by administration of indomethacin ( 1 10 mg kg ( 1 ) ) , NS 398 ( 0 . 4 4 mg kg ( 1 ) ) or DFU ( 0 . 02 2 mg kg ( 1 ) ) as assessed macroscopically and histologically . 3 . ^^^ Low doses of 16 , 16 dimethyl prostaglandin ( PG ) E ( 2 ) , that did not protect against ethanol induced mucosal damage , reversed the effects of the selective COX 2 inhibitors , indomethacin and dexamethasone . 5 . 1 R had no effect on gastric COX 1 mRNA levels but increased COX 2 mRNA levels in a time dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery that there are two pathways to influence cyclooxygenase activity and prostaglandin production and that some NSAIDs have a more marked COX 2 and COX 1 inhibition opens new perspectives . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two COX isoenzymes ( constitutive or COX 1 and inducible or COX 2 ) have been described in the rat kidney . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , the role of the cyclooxygenase isoenzymes COX 1 and COX 2 during chronic exposure to TCDD was studied in more detail . ^^^ Long term treatment with TCDD ( 4 7 weeks ) induced the expression of COX 1 and COX 2 mRNA in C3H / M2 fibroblasts ( up to 2 fold ) . ^^^ However , in contrast to TPA , the TCDD mediated enhancement of malignant cell transformation may not specifically depend on the induction of COX 2 but , additionally , the induction of COX 1 activity may be necessary . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , mRNA expression of the inducible form of cyclooxygenase ( COX 2 ) , but not the constitutive form ( COX 1 ) , the major enzymes in prostaglandin production , was increased by PFF . ^^^ We subjected bone cells originating from the iliac crest of nine elderly women , between 56 and 80 yr of age , for 1 h to PFF and measured prostaglandin production and COX 1 and COX 2 mRNA expression . ^^^ PFF also increased the expression of COX 2 mRNA by 2 . 9 fold , but did not change COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We examined the expression of the PGH 2 synthases , cyclooxygenase 1 ( COX 1 ) and COX 2 , in uterine tissues during late pregnancy , using PGF receptor deficient ( FP / ) mice . ^^^ Thus , in uterine tissues , myometrial expression of COX 2 is closely associated with the occurrence of parturition , but uterine expression of COX 1 is induced much earlier and kept at a high level until parturition occurs . ^^^ These results suggest that COX 1 derived PGs are responsible for the induction of luteolysis , and that COX 2 derived PGs play a role in the final pathway of parturition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A nonspecific COX inhibitor , not a specific COX 2 inhibitor , reduced growth and angiogenesis of non COX expressing cancer xenograft by inhibition of COX 1 in vascular endothelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These agents preserve the COX 1 that is responsible for the production of cytoprotective prostaglandins in the stomach and selectively inhibit COX 2 induced at the sites of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our data show that incorporation of n 3 fatty acids ( but not other polyunsaturated or saturated fatty acids ) into articular cartilage chondrocyte membranes results in a dose dependent reduction in : ( 1 ) the expression and activity of proteoglycan degrading enzymes ( aggrecanases ) and ( 2 ) the expression of inflammation inducible cytokines ( interleukin ( IL ) 1alpha and tumor necrosis factor ( TNF ) alpha ) and cyclooxygenase ( COX 2 ) , but not the constitutively expressed cyclooxygenase COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several studies have demonstrated that COX 1 and COX 2 inhibitors could inhibit the in vitro growth of human lung cancer cell lines . ^^^ In this report , we evaluated the growth inhibitory effects of sulindac sulfide , a COX 1 and COX 2 inhibitor ; exisulind ( sulindac sulfone ) , a novel proapoptotic agent that does not inhibit COX enzymes ; and nordihydroguaiaretic acid ( NDGA ) , a lipoxygenase inhibitor on human lung cancer cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The central tenets of the rationale for developing selective COX 2 inhibitors are that prostaglandins that contribute to inflammation are derived from COX 2 , whereas prostaglandins that are involved in normal physiological processes are derived from the constitutively expressed isoform COX 1 . ^^^ Moreover , there is strong evidence that COX 1 contributes to inflammation and pain , so selective inhibition of COX 2 will not necessarily produce the same degree of efficacy that is seen with mixed inhibitors of COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro analysis of COX 2 / COX 1 ratios requires consideration of the target tissues being examined , the details of incubation periods , outcome measures , and other parameters . ^^^ Based on approximate equipotence , highly selective COX 2 inhibitors may cause fewer peptic ulcers and bleeds than drugs that are COX 1 preferential . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although recognition of the differential activities of new and established NSAIDs on the activities of the cyclooxygenases ( COXs ) affecting production of inflammatory prostaglandins ( from COX 2 ) and those that are physiologically important ( from COX 1 ) may have significance for the prostaglandin components of the underlying inflammatory and physiologic processes , there are important features of their chemical structures that determine the various cellular and biochemical actions of these agents . ^^^ These physicochemical properties may contribute to the low irritancy of the new COX 2 selective drugs quite apart from their sparing of COX 1 in the GI mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is expressed in most tissues , whereas COX 2 usually is absent , but is induced by numerous physiologic stimuli . ^^^ Surprisingly , disruption of Cox 1 ( Ptgs 1 ) in the mouse did not result in gastrointestinal abnormalities . cox 2 ( Ptgs 2 ) null mice show reproductive anomalies and defects in kidney development . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , the enzyme cyclooxygenase ( COX ) has been recognized to exist as constitutive ( COX 1 ) and inducible isoforms ( COX 2 ) . ^^^ In previous studies , drugs that were inhibitors of both COX 1 and COX 2 failed to decrease brain edema formation or improve Neurological Severity Score ( NSS ) after closed head trauma ( CHT ) , although some did decrease prostaglandin E 2 ( PGE 2 ) formation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoenzymes of cyclooxygenase COX 1 and COX 2 in the late eighties was followed by an intensive looking for drugs , which inhibit specifically COX 2 and have no influence on COX 1 . ^^^ CSI firstly inhibit COX 1 / COX 2 to a different extent and in a different manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To investigate the possible contribution of COX 2 expression in platelet thromboxane ( TX ) biosynthesis , we have compared the inhibitory effects of NS 398 and aspirin , selective inhibitors of COX 2 and COX 1 , respectively , on prostanoid biosynthesis by thrombin stimulated platelets vs lipopolysaccharide ( LPS ) stimulated monocytes ( expressing high levels of COX 2 ) isolated from whole blood of healthy subjects . ^^^ By using specific Western blot techniques , we failed to detect COX 2 in platelets while COX 1 was readily detectable . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Derivatization of the carboxylate moiety in moderately selective COX 1 inhibitors , such as 5 , 8 , 11 , 14 eicosatetraynoic acid ( ETYA ) and arylacetic and fenamic acid NSAIDs , exemplified by indomethacin and meclofenamic acid , respectively , generated potent and selective COX 2 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX 1 or COX 2 ) have been identified in the prostanoid biosynthetic pathway . ^^^ The constitutive form , COX 1 , is thought to maintain cellular homeostasis and the inducible form , COX 2 , is recognized as a primary response gene thought to be involved in modulating cell proliferation and differentiation . ^^^ To further characterize the role of the cyclooxygenases in cell proliferation , differentiation , and tumorigenicity we developed embryonic stem ( ES ) cell lines which contain homozygous disruptions in either the COX 1 or the COX 2 gene . ^^^ Our results demonstrate that the wild type ES cells do not express either COX 1 or COX 2 until the cells undergo differentiation . ^^^ Histological microscopy shows that the few very small tumors that were generated from ES cells lacking COX 2 appear more differentiated than tumors emerging from COX 1 / or wild type cells by exhibiting greater keratinization in the areas of squamous epithelium and the ossification of bone forming cartilage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although effective analgesic and anti inflammatory agents , NSAIDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 in health and disease . ^^^ It is now known that COX exists as two distinct but similar isozymes , COX 1 and COX 2 . ^^^ Prostaglandins ( PGs ) formed by the enzymatic activity of COX 1 are primarily involved in the regulation of homeostatic functions throughout the body , whereas PGs formed by COX 2 primarily mediate pain and inflammation . ^^^ Based on structural differences in the active sites of COX 1 and COX 2 , a new class of drugs has been developed that specifically inhibits COX 2 but not COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Preclinical studies of celecoxib in vitro and in vivo support the COX 2 hypothesis that the therapeutic effects of NSAIDs are due to the inhibition of COX 2 , and the adverse events associated with NSAID therapy are due to the inhibition of cyclooxygenase 1 ( COX 1 ) , the constitutively expressed isoform of COX . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two separate isoforms , COX 1 and COX 2 , are present , and differences in their roles are discussed in the context of inflammation and parturition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Celecoxib ( Celebrex ) is the first of a new family of nonsteroidal anti inflammatory drugs ( NSAIDs ) that selectively inhibit cyclooxygenase 2 ( COX 2 ) while sparing COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression level of COX 2 mRNA increased in a time dependent manner , although COX 1 mRNA was constantly expressed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Based on RT PCR and Northern blot analysis , resting zone chondrocytes express mRNAs for both Cox 1 and Cox 2 . ^^^ To examine the role of Cox , the cultures were also treated with resveratrol ( a specific inhibitor of Cox 1 ) , NS 398 ( a specific inhibitor of Cox 2 ) , or indomethacin ( a general Cox inhibitor ) . ^^^ In contrast , inhibition of Cox 2 had no effect , indicating that 24R , 25 ( OH ) ( 2 ) D ( 3 ) exerts its effects via Cox 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Conventional nonsteroidal anti inflammatory drugs ( NSAIDs ) nonspecifically inhibit cyclooxygenase 1 ( COX 1 ) , an enzyme critical to normal platelet function , and COX 2 , which mediates inflammatory response mechanisms . ^^^ Celecoxib , an antiarthritic agent that inhibits COX 2 but spares COX 1 at therapeutic doses , is expected to have minimal effects on platelet function . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is now clear that COX 1 is expressed in the majority of cells constitutively , and COX 2 appears after stimulation . ^^^ Monoclonal antibodies against COX total ( detecting both COX 1 and COX 2 epitopes ) and anti COX 2 combined with peroxidase antiperoxidase ( PAP ) visualizing system were used to assess COX total and COX 2 expression in cryostat sections of nasal polyps from both groups of patients . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is utilized only in the immediate response and COX 2 is a prerequisite for the delayed response . ^^^ The induced immediate response is often mediated by COX 2 rather than by COX 1 , especially when the end product is PGE 2 . ^^^ Moreover , differential coupling between COXs and downstream terminal PG synthases is also evident in macrophages , in which COX 1 and COX 2 are preferentially coupled with TXS and PGES , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because traditional NSAIDs inhibit both COX 1 and COX 2 , these drugs induce side effects , such as gastrointestinal ulceration and renal toxicity , through the inhibition of the constitutive COX 1 . ^^^ Our previous study has shown that celecoxib , an inhibitor of COX 2 , while sparing COX 1 , inhibited azoxymethane ( AOM ) induced colon tumorigenesis when administered during both initiation and postinitiation stages , ie . , celecoxib administered continuously before , during , and after carcinogen treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Anti inflammatories that selectively inhibit inducible cyclooxygenase ( COX ) 2 are being investigated in colon as alternatives to the NSAID , which inhibit both COX 1 and COX 2 and derive their toxicity from COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is expressed constitutively in most tissues , and COX 2 is induced by a wide variety of stimuli and was initially identified as an immediate early growth response gene . ^^^ In addition , COX 2 expression is markedly increased in 85 90 % of human colorectal adenocarcinomas , whereas COX 1 levels remain unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While normal blood vessels expressed the COX 1 enzyme , new angiogenic endothelial cells expressed the inducible COX 2 . ^^^ Indomethacin ( a nonselective COX 1 / COX 2 inhibitor ) and SC 236 ( a COX 2 selective inhibitor ) inhibited angiogenesis in a dose dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 protein and mRNA expression was determined by BMMC in the presence of KL , LPS and IL 10 . ^^^ RESULTS : Rutaecarpine inhibited COX 2 and COX 1 dependent phases of PGD 2 generation in BMMC in a concentration dependent manner with an IC 50 of 0 . 28 microM and 8 . 7 microM , respectively . ^^^ However , rutaecarpine inhibited neither PLA 2 and COX 1 activity nor COX 2 protein and mRNA expression up to the concentration of 30 microM in BMMC , indicating that rutaecarpine directly inhibited COX 2 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent discovery that there are two forms of cyclooxygenase ( COX 1 and COX 2 ) has led to hypothesis that the newly marketed COX 2 selective inhibitor can provide beneficial effects without these adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins , potent mediators of inflammation , are generated from arachidonic acid ( AA ) via the action of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Agents have been developed that can selectively inhibit the COX 2 isoform , while sparing COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Roles of cyclooxygenases ( COX 1 and COX 2 ) and nitric oxide ( NO ) synthases ( nNOS and iNOS ) in adaptive cytoprotection induced by 20 mM taurocholate dissolved in 50 mM HCl ( TC ) were investigated in rat stomachs . ^^^ The early phase is mediated mainly by COX 1 / PGs , while the later phase is mediated by iNOS / NO , in addition to prostaglandins ( PGs ) produced by both COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results suggest that 1 ) hypothermic stress caused an increase of acid secretion and motility as well as a decrease of duodenal HCO 3 secretion , resulting in damage in both the stomach and duodenum , 2 ) the COX 1 but not COX 2 inhibition worsened these lesions by enhancing gastric motility and further decreasing duodenal HCO 3 response , 3 ) the cNOS but not iNOS inhibition worsened gastric lesions by increasing acid secretion but decreased duodenal damage by increasing HCO 3 secretion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonselective nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit both the COX 1 and COX 2 protein , the two enzymes that convert arachidonic acids to prostaglandins . ^^^ COX 2 , but not COX 1 , is highly expressed in human colon carcinoma , squamous cell carcinoma of the esophagus , and skin cancer . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast to its effect on COX 2 expression , SNAP did not affect the constitutive expression of COX 1 in rheumatoid synovial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In cells co transfected with cytosolic PLA 2 ( cPLA 2 ) and COX 1 or COX 2 , phorbol ester + ionomycin markedly stimulated PGE 2 production . ^^^ In contrast , group IIA secretory PLA 2 ( sPLA 2 ) co transfected with COX 1 or COX 2 did not lead to an increase in PGE 2 production , despite high levels of sPLA 2 enzymatic activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effects of selective inhibitors of cyclo oxygenase 1 ( COX 1 ) and cyclo oxygenase 2 ( COX 2 ) on the spontaneous myogenic contractions in the upper urinary tract of the guinea pig and rat . ^^^ The role of cyclo oxygenase 1 ( COX 1 ) and cyclo oxygenase 2 ( COX 2 ) in the upper urinary tract of the guinea pig and rat was examined using simultaneous tension recordings of the proximal and distal regions of the renal pelvis and the ureter . ^^^ Moreover COX 2 is the primary enzyme involved in synthesizing PGs in the guinea pig upper urinary tract , while COX 1 appears to be the predominantly active enzyme in the rat . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To investigate roles in intestinal inflammation for the 2 cyclooxygenase ( COX ) isoforms , we determined susceptibility to spontaneous and induced acute colitis in mice lacking either the COX 1 or COX 2 isoform . ^^^ We treated wild type , COX 1 ( / ) , COX 2 ( / ) , and heterozygous mice with dextran sodium sulfate ( DSS ) to provoke acute colonic inflammation , and we quantified tissue damage , prostaglandin ( PG ) E ( 2 ) , and interleukin 1beta . ^^^ Both COX 1 ( / ) and COX 2 ( / ) mice showed increased susceptibility to a low dose of DSS that caused mild colonic epithelial injury in wild type mice . ^^^ COX 2 ( / ) mice were more susceptible than COX 1 ( / ) mice , and selective pharmacologic blockade of COX 2 potentiated injury in COX 1 ( / ) mice . ^^^ These results demonstrate that COX 1 and COX 2 share a crucial role in the defense of the intestinal mucosa ( with inducible COX 2 being perhaps more active during inflammation ) and that neither isoform is essential in maintaining mucosal homeostasis in the absence of injurious stimuli . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have attempted to determine a relationship between tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis , COX 1 , and COX 2 in tumor tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ovine endometrium showed transient expression of high concentrations of the inducible isoform of cyclooxygenase , cyclooxygenase 2 ( COX 2 ) , whereas the constitutive isoform , cyclooxygenase 1 ( COX 1 ) , was expressed at much lower concentrations and did not change . ^^^ Endometrial cells from cyclic or pregnant ewes at days 9 , 12 , 14 and 16 were isolated and analysed for the presence of COX 1 and COX 2 proteins using western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The presence of COX 1 and COX 2 protein was determined using Western analysis . ^^^ The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX 2 selective inhibitor , SC 236 , or a COX 1 selective inhibitor , SC 560 , and measurement of prostaglandin release during 24 h using enzyme linked immuno sorbent assay ( ELISA ) . ^^^ RESULTS : Both COX 1 and COX 2 protein were demonstrated in amnion and chorion decidua . ^^^ CONCLUSIONS : Fetal membranes contain both COX 1 and COX 2 at term , but only COX 2 contributes towards prostaglandin synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two isoforms of cyclooxygenase , COX 1 and COX 2 , are acetylated by aspirin at Ser 530 and Ser 516 , respectively , in the cyclooxygenase active site . ^^^ Acetylated COX 2 is essentially a lipoxygenase , making 15 ( R ) hydroxyeicosatetraenoic acid ( 15 HETE ) and 11 ( R ) hydroxyeicosatetraenoic acid ( 11 HETE ) , whereas acetylated COX 1 is unable to oxidize arachidonic acid to any products . ^^^ Site directed mutagenesis of Val 434 , Arg 513 , and Val 523 in mouse COX 2 to their COX 1 equivalents resulted in abrogation of 11 and 15 HETE production after aspirin treatment , confirming the hypothesis that these residues are the major isoform selectivity determinants regulating HETE production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study investigated the effects of shear stress on gene expression of prostacyclin synthesis related enzymes cyclooxygenases ( COX 1 and COX 2 ) , prostacyclin synthase ( PGS ) , and thromboxane synthase ( TXS ) and their metabolites prostaglandin ( PGI ( 2 ) ) and thromboxane A ( 2 ) ( TXA ( 2 ) ) in endothelium of intact conduit vessels . ^^^ COX 1 and COX 2 mRNA showed a biphasic response with peaks at 1 . 5 and 6 hours , with a nadir level at 3 hours . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 , and COX 3 and the future treatment of chronic inflammatory disease . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ibuprofen significantly decreased levels of gene expression of both COX 1 and COX 2 ( p < 0 . 01 ) . ^^^ Although dietary 4 HPR did significantly diminish levels of COX 1 gene expression ( p < 0 . 01 ) in rat mammary adenocarcinomas , this synthetic retinoid did not significantly inhibit COX 2 gene expression . ^^^ COX 1 protein was localized to endothelial cells , infiltrating inflammatory cells , and tumor cells , while COX 2 protein was detected primarily within tumor cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
None of these active compounds affected iNOS , COX 2 , COX 1 or PLA 2 activities , although some reduced iNOS or COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RATIONALE FOR THE USE OF SELECTIVE COX 2 INHIBITORS : The rationale for the prescription of selective COX 2 inhibitors as neuroprotective drugs in AD lies on : Epidemiological data having shown a reduced risk of developing AD in patients treated with anti inflammatory doses of classical NSAIDs ( inhibition of COX 1 and COX 2 ) but not with antithrombotic doses of aspirin ( selective inhibition of COX 1 ) , Cellular experiments , Demonstration of a better gastro intestinal ( GI ) safety profile with selective COX 2 inhibitors than with classical NSAIDs in short term studies , allowing a possible long term use in AD . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We compared the efficacy , safety , and tolerability of long term therapy with celecoxib , a COX 1 sparing inhibitor of COX 2 , with diclofenac , a non specific COX inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is believed that prostanoids produced by COX 1 activity are essential for the physiological functions of tissues while those produced by COX 2 lead to various pathological changes in these tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 mRNA and protein expression were also suppressed only by COX 2 AS ODN without any alteration of COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to investigate the expression and localization of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) in synovial tissues from patients with rheumatoid arthritis ( RA ) . ^^^ Synovial tissues from 9 patients with RA and 5 patients with osteoarthritis ( OA ) were examined for COX 1 and COX 2 expressions by immunohistochemical staining using 2 polydonal COX 1 and COX 2 antibodies . ^^^ The localization of COX 2 expression dearly differed from that of COX 1 expression , being most intense in inflammatory cells . ^^^ However , there was no difference in COX 1 and COX 2 expressions between RA and OA synovial tissues . ^^^ Our observations support that inflammatory mechanisms modulated by COX 1 and COX 2 in chronic RA synovium might be similar to those in chronic OA synovium . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is found that nimesulide exploits the extra space made available by the replacement at position 523 of an isoleucine residue in COX 1 by a valine in COX 2 and establishes electrostatic interactions with both Arg 106 and Arg 499 ( Arg 120 and Arg 513 in PGHS 1 numbering ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Auranofin showed no effect on the enzyme activities of the purified COX 1 and COX 2 proteins . ^^^ Furthermore , auranofin did not affect the COX 1 protein level , but inhibited the TPA induced expression of COX 2 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This article outlines the mechanisms involved in specific cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibition as they relate to the safety of nonsteroidal anti inflammatory drug ( NSAID ) use . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One is cPLA ( 2 ) phosphorylation through a signal transduction pathway from PI 3 kinase to p44 / 42 MAP kinases , by which arachidonic acid , a substrate for COX 1 and COX 2 , is increased . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Experiments with purified COX 1 and COX 2 also showed 9 fold increase of 3 nitrotyrosine levels , which correlated with decreased ( 93 98 % ) production of prostaglandin H ( 2 ) when ONOO ( ) ( 50 microM ) was added 1 min before arachidonic acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 proteins and mRNA were measured by western and northern blot , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 1 is expressed ubiquitously , COX 2 is an immediate early gene often associated with malignant transformation , and a role for the COX enzymes in tumor initiation and promotion is discussed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cox inhibitors ( Cox 1 and Cox 2 ) decreased tumor growth by 35 40 % in MCG 101 bearing mice but had no such effect on melanoma bearing mice , despite the expression of the Cox 2 protein in melanoma cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
FGF 2 at 10 ( 9 ) M and higher concentrations induced osteoclastic cell formation in the coculture system of mouse osteoblastic cells and bone marrow cells , and this induction was abrogated by nonsteroidal anti inflammatory drugs ( NSAIDs ) . 45Ca release from prelabeled cultured mouse calvariae stimulated by FGF 2 ( 10 ( 8 ) M ) was also inhibited by NSAIDs , and the inhibition was stronger by NSAIDs , which are more selective for inhibition of cyclooxygenase 2 ( COX 2 ) than COX 1 , suggesting the mediation of COX 2 induction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( Cox ) , the key enzyme of prostanoid synthesis , consists of the two isoforms Cox 1 and Cox 2 , both recently noted to be constitutively expressed in rat lungs with a distinct profile of cellular distribution . ^^^ The responsiveness of pulmonary Cox 1 and Cox 2 expression to intravascular endotoxin lipopolysaccharide ( LPS ) administration was investigated in isolated , ventilated rat lungs , buffer perfused with or without admixture of rat plasma . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
High cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) contents in mouse lung tumors . ^^^ Because enhanced cyclooxygenase 2 ( COX 2 ) expression has been observed in advanced human AC , we investigated the intracellular concentrations of the two cyclooxygenases , cyclooxygenase 1 ( COX 1 ) and COX 2 , at different times after carcinogen administration to A / J mice . ^^^ The concentrations of both proteins were much higher in urethane induced adenomas and carcinomas compared with control A / J mouse lung tissue ( P < 0 . 03 and P < 0 . 01 in adenomas and AC , respectively , for COX 1 ; P < 0 . 003 and P < 0 . 004 in adenomas and AC , respectively , for COX 2 ) . ^^^ Small benign tumors that arose spontaneously in 13 month old mice also stained for COX 1 and COX 2 , showing that this elevated enzyme content does not depend on chemical induction . ^^^ COX 1 and COX 2 immunostaining was observed in normal bronchiolar and alveolar epithelia , alveolar macrophages and bronchiolar smooth muscle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery that proinflammatory prostaglandins are produced by cyclooxygenase 2 ( COX 2 ) , an inducible isoform of the constitutive cyclooxygenase 1 ( COX 1 ) , opened a new frontier in the treatment of inflammatory diseases , because the selective inhibition of COX 2 can lead to therapeutically effective compounds which do not have the common side effects of classical non steroidal antiinflammatory drugs ( NSAIDs ) . ^^^ Different crystallographic structures of both free COX 1 and COX 2 as well as complexes with inhibitors have been solved . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the Freund ' s adjuvant model of monoarthritis , the proportion of cox 1 positive DRG neurons was unchanged and no neurons were found to be labelled for cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoform of cyclooxygenase ( COX 1 and COX 2 ) have now been identified , each possessing similar activities , but differing in characteristic tissue expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , non COX 2 selective arylethersulfonamides , including a highly selective COX 1 inhibitor , inhibited human and murine COX 2 approximately equipotently . ^^^ We suggest these differing in vitro in vivo effects observed could be due to significant inflammatory prostaglandin synthesis by COX 1 , or to the genetic differences between human and rodent COX 2 , or to both . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results indicate that BK induced epithelium dependent relaxation in the guinea pig bronchus is partially mediated by release of NO or by NO related substances , involving an activation of both cyclo oxygenase 1 ( COX 1 ) and COX 2 enzymes , through a cyclic guanosine monophosphate ( cGMP ) independent mechanism . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Also , to compare the effect of a COX 2 inhibitor with that of a nonselective COX 1 and COX 2 inhibitor and B 2 receptor antagonist . ^^^ JTE 522 ( 1 100 mg 10 kg ( 1 ) ) , a COX 2 inhibitor , indomethacin ( 1 30 mg 10 kg ( 1 ) ) , a nonselective COX 1 and COX 2 inhibitor , or FR 173657 ( 10 and 100 mg 10 kg ( 1 ) ) , a bradykinin B 2 receptor antagonist , was administered orally five minutes after the end of the surgery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Epidemiological and clinical studies in humans indicate that the entire class of nonsteroidal anti inflammatory drugs ( NSAIDs ) that inhibit both COX 1 and COX 2 enzymes are promising colon cancer chemopreventive agents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase isozymes ( COX 1 and COX 2 ) are found to be constitutively expressed in brain , with neuronal expression of COX 2 being rapidly induced after numerous insults , including cerebral ischemia . ^^^ Immunocytochemical analysis of mixed cortical cell cultures revealed that COX 2 expression was restricted to neurons , whereas COX 1 was expressed in both neurons and astrocytes . ^^^ Flurbiprofen , a nonselective COX 1 / COX 2 inhibitor , blocked NMDA stimulated PG production and attenuated neuronal death in a concentration dependent manner . ^^^ Similar results were obtained with the specific COX 2 inhibitor NS 398 ( 10 30 microM ) but not with the selective COX 1 inhibitor valeryl salicylate ( 10 300 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In segments of colon mounted in Ussing chambers , arachidonic acid caused a concentration dependent increase in short circuit current that was blocked by piroxicam , the COX 2 inhibitor NS 398 , and the COX 1 inhibitor SC 560 . ^^^ These data demonstrate that both COX 1 and COX 2 are constitutively expressed in the mouse colon , and both contribute to PG dependent electrolyte transport . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX inhibitors have different selectivities for the two COX isoenzymes ( COX 1 and COX 2 ) which vary between purified enzyme and intact cell preparations . ^^^ A number of COX inhibitors in cultured human airway cells were compared which exclusively express either COX 1 ( primary degree cultured human airway smooth muscle ( HASM ) cells ) or COX 2 ( A 549 pulmonary epithelial cell line ) as measured by Western blotting . ^^^ The COX 2 : COX 1 selectivity ratio ( COX 2 IC50 / COX 1 IC 50 ) was < 0 . 0001 for nimesulide , 0 . 001 for NS 398 , 0 . 03 for flurbiprofen and 1 . 9 for indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tumor necrosis factor alpha ( TNF alpha ) and angiotensin 2 ( Ang 2 ) induced a transient increase in vascular smooth muscle cell ( VSMC ) cyclooxygenase 2 ( COX 2 ) mRNA accumulation , without affecting COX 1 mRNA levels . ^^^ Prostacyclin 1 ( 2 ) synthesis was tightly coupled to expression of COX 2 , whereas prostaglandin E ( 2 ) and thromboxane A ( 2 ) ( TXA ( 2 ) ) synthesis may be associated with differential usage of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There was no evidence for assembly of COX 1 , COX 2 , or COX 3 subunits in a multisubunit complex in cells homoplasmic for the mutation , thus indicating that there was no stable assembly of COX 1 with COX 2 in the absence of wild type COX 3 . ^^^ In contrast , the COX 1 and COX 2 subunits were assembled in cells with 97 % mutated mtDNA . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONTEXT : In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 ( COX 2 ) but not COX 1 , suggesting that this drug may have anti inflammatory and analgesic activity without adverse upper gastrointestinal ( GI ) tract effects that result from COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins ( PG ) derived from COX 1 play an important role in the maintenance of mucosal integrity but the role of COX 2 derived products in mucosal defence mechanism has not been fully explained . ^^^ In this study , the mucosal expression of COX 1 and COX 2 was examined and the inhibitors of these enzymes were used to determine the contribution of these enzymes in adaptive cytoprotection induced by mild stress . ^^^ Male Wistar rats were exposed to mild water immersion and restraint stress ( WRS ) at various time intervals ranging from 5 min up to 2 h followed 1 h later by exposure to severe 3 . 5 h WRS with or without pretreatment with : 1 ) NS 398 ( 10 mg 10 kg ( 1 ) i . g . ) , a selective COX 2 inhibitor ; 2 ) resveratrol ( 5 mg 10 kg ( 1 ) i . g . ) , a selective COX 1 inhibitor ; 3 ) meloxicam ( 2 mg 10 kg ( 1 ) i . g . ) , preferential COX 2 inhibitor ; and 4 ) indomethacin ( 5 mg 10 kg ( 1 ) i . p ) , non selective inhibitor of COX . ^^^ The number of WRS lesions was counted , gastric blood flow ( GBF ) was measured by H 2 gas clearance technique , mucosal biopsy samples were taken for the assessment of PGE 2 by radioimmunoassay , and the expression of COX 1 and COX 2 mRNA by RT PCR . ^^^ We conclude that PG derived from both , COX 1 and COX 2 appear to be involved in adaptive cytoprotection developed in response to mild stressors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of the COX enzyme , COX 1 and COX 2 . ^^^ Normal physiological functions are mediated by ' constitutive ' COX 1 , while the inflammatory response is mediated by ' inducible ' COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of eNOS , iNOS , and inducible ( COX 2 ) and constitutive ( COX 1 ) cyclooxygenase was examined with Western blotting and reverse transcription polymerase chain reaction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROCEDURE : COX 1 and COX 2 were evaluated by use of isoform specific antibodies with standard immunohistochemical methods . ^^^ RESULT : COX 1 , but not COX 2 , was constitutively expressed in normal urinary bladder epithelium ; however , COX 2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Celecoxib is a cyclo oxygenase ( COX ) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX 2 over COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The intergenomic coevolution of interacting gene products has been previously suggested based on interspecific comparisons of cytochrome c ( encoded by the nuclear CYC gene ) and cytochrome c oxidase ( partly encoded in the mitochondrial DNA by the COX 1 , COX 2 and COX 3 genes ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Gastric and duodenal tissues were collected intraoperatively from nine and four patients , respectively , and immunohistochemical staining for COX 1 and COX 2 was performed . ^^^ The COX 1 protein was not detected , whereas COX 2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase have been described , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^ COX 2 levels are 2 50 fold higher than levels in adjacent normal intestinal mucosa , while COX 1 levels are unchanged . ^^^ These observations raise the question : Does COX 1 or COX 2 provide a useful target for prevention or treatment of colorectal cancer ? . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present work evaluates the effects of the COX 1 / COX 2 inhibitor dexketoprofen as well as of a selective COX 2 inhibitor , NS 398 , on urodynamic function following endotoxin ( LPS ) or cyclophosphamide ( CYP ) induced inflammation of the urinary bladder . ^^^ These results indicate that COX 1 may be involved in modulating the threshold for activating the micturition reflex in the normal rats and also demonstrates that inhibition of COX 2 prevents or reverses the urodynamic changes associated with bladder inflammation induced either by surgery , LPS or CYP treatments . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the rate limiting enzyme for prostaglandin synthesis , exists in two isoforms , COX 1 and COX 2 . ^^^ Levels of COX 1 and COX 2 were similarly expressed in the normal stomach . ^^^ When ulcers were undergoing healing and repair , COX 1 and COX 2 mRNA levels were significantly elevated . ^^^ Age related changes in COX 1 and COX 1SV but not COX 2 mRNA may alter gastric mucosal cytoprotection . ^^^ Furthermore , COX 1 and COX 2 may both contribute to the healing of a gastric ulcer . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , wild type and P 4 treated PRLR / mice had similar expression of the implantation specific genes , LIF , amphiregulin , HB EGF , COX 1 , COX 2 , PPARdelta , Hoxa 10 , cyclin D 3 , VEGF , and its receptors , Flk 1 and neuropilin 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : To investigate immunohistochemically the cellular distribution of COX 1 and COX 2 proteins in the human stomach with or without gastritis or ulceration . ^^^ Electron microscopic immunohistochemistry revealed both COX 1 and COX 2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These studies indicate that ( a ) although COX 2 predominates , both COX isozymes are induced and contribute to the prostaglandin response to LPS in humans ; ( b ) COX activation contributes undetectably to lipid peroxidation induced by LPS ; and ( c ) COX 2 , but not COX 1 , contributes to the constitutional response to LPS in humans . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RT PCR failed to detect any change in levels of nNOS , eNOS , iNOS , COX 1 or COX 2 mRNAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Focal accumulation of cyclooxygenase 1 ( COX 1 ) and COX 2 expressing cells in cerebral malaria . ^^^ We have now analyzed expression of COX 1 and COX 2 in brains of patients with CM by immunohistochemistry . ^^^ Double labeling experiments were used to verify the cellular identity of COX 1 and COX 2 expressing cells . ^^^ The restricted expression and accumulation of COX 1 and COX 2 in CM brains adds convincing evidence for the participation of cyclooxygenases in the formation of fever , inflammation and granuloma in these patients . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , which exists as COX 1 and COX 2 isoforms , is the first enzyme in the pathway in which arachidonic acid is converted to PGs . ^^^ COX 1 and COX 2 protein was measured by immunoblotting using specific antibody . ^^^ Untreated HUVEC contained only COX 1 protein while IL 1beta treated HUVEC contained COX 1 and COX 2 protein . ^^^ Interestingly , PGE 2 ( 3 microM for 24h ) can inhibit COX 2 protein , but not COX 1 protein , expressed in HUVEC treated with IL 1beta . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Notable features of D . discoideum mtDNA include the following . ( 1 ) All genes are encoded on the same strand of the DNA and a universal genetic code is used . ( 2 ) The cox 1 gene has no termination codon and is fused to the downstream cox 2 gene . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After salt loading , the expression of COX 1 was enhanced in the medulla and that of COX 2 reduced in the cortex . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) are the enzymes responsible for the biosynthesis of the precursor to the biologically active prostaglandins , prostacyclin , and thromboxane and are the molecular targets for nonsteroidal antiinflammatory drugs ( NSAIDs ) . ^^^ Selective COX 2 inhibitors are antiinflammatory and analgesic but lack gastrointestinal toxicity , an undesirable side effect attributed to COX 1 inhibition . ^^^ We employed rapid mixing techniques and fluorescence quenching to monitor the association and dissociation of a selective COX 2 inhibitor to COX 1 or COX 2 . ^^^ Its binding to COX 2 occurs in three kinetically distinct steps whereas its binding to COX 1 occurs in two steps . ^^^ In contrast to the relatively rapid association of SC 299 with both enzymes , its dissociation from COX 2 is quite slow and occurs over several hours whereas the dissociation from COX 1 is complete in less than 1 min . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In sponge granuloma , mRNA of COX 1 was constitutively expressed , whereas that of COX 2 was increased with neovascularization in parallel with that of vascular endothelial growth factor ( VEGF ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We observed that AA and PGs induced COX 2 , as well as COX 1 , expression in cultured murine keratinocytes approximately 3 h after treatment . ^^^ Forskolin , a known activator of adenylate cyclase , and dibutryl cAMP , a cAMP analog , induced COX 1 and COX 2 mRNA , suggesting that cAMP is a second messenger for COX expression . ^^^ The results of this study demonstrate that both COX 1 and COX 2 are inducible . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Many of the effects on platelet functioning , RBF , and the GI tract may be eliminated with the introduction of NSAIDs that selectively inhibit COX 2 without effects on COX 1 , the enzyme present in the GI tract , renal system , and platelets . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists in 2 isomeric forms , COX 1 and COX 2 , which are inhibited to different extents by the classical NSAIDs . ^^^ The selective COX concept predicts that inhibition of COX 1 may result in gastrointestinal adverse effects , whereas inhibition of COX 2 may underlie the anti inflammatory actions of NSAIDs . ^^^ These observations have led to the development of new drugs with high inhibitory potency for COX 2 and low potency for COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Fortunately , 2 forms of COX enzymes , designated COX 1 and COX 2 , have been recognised . ^^^ COX 1 appears to function as a house keeping enzyme , whereas COX 2 is primarily induced by inflammatory stimuli and mitogens in various cells , including macrophages and synovial cells . ^^^ Accordingly , the inhibition of COX 2 would result in anti inflammatory effects , whereas gastroduodenal ulceration is thought to be related to the inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We evaluated the contribution of host derived COX 1 and COX 2 in tumor growth using both genetic and pharmacological approaches . ^^^ We found that tumor growth was markedly attenuated in COX 2 ( / ) , but not COX 1 ( / ) or wild type mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This down regulation of PGE 2 formation involved the inhibition of the inducible COX 2 isoform expression both at the transcriptional and translational levels , whereas expression of the constitutive COX 1 isoform was unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results indicate that IL 1beta induced delayed PGE ( 2 ) generation in these human fibroblasts mainly depends on de novo induction of COX 2 and cPLA ( 2 ) , irrespective of the constitutive presence of COX 1 , and that IFN gamma and IL 4 inhibit IL 1beta induced delayed PGE ( 2 ) generation by suppressing , predominantly , COX 2 expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We demonstrate that COX 2 , but not COX 1 , is induced during inflammation mediated PTL caused by lipopolysaccharide ( LPS ) administration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The nonselective COX 1 / COX 2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the whole blood assays , the COX 2 / COX 1 ratio for meloxicam was 0 . 2 compared to 0 . 9 for indomethacin confirming meloxicam ' s COX 2 selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , amfenac was a potent inhibitor of both COX 1 ( IC 50 = 0 . 25 microM ) and COX 2 activity ( IC 50 = 0 . 15 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the regulation of whole blood cyclooxygenase 1 and 2 ( COX 2 and COX 1 ) activities by methotrexate ( MTX ) in rheumatoid arthritis ( RA ) patients . ^^^ COX 1 activity was quantified as platelet thromboxane B ( 2 ) production in unstimulated blood and COX 2 activity was measured as prostaglandin E ( 2 ) ( PGE ( 2 ) ) production in whole blood stimulated with LPS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When stimulated with sublytic C5b 9 , COX 2 was significantly up regulated , whereas COX 1 was not affected . ^^^ Glomeruli from rats with PHN expressed significantly more COX 1 and COX 2 , as compared with normal rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This is attributed to increased levels of COX 2 specific mRNA , increased amounts of COX 2 protein and COX enzyme activity in the absence of detectable COX 1 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Clinical data on COX 1 and COX 2 inhibitors : what possible alerts in pharmacovigilance ? ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , ebselen inhibits LPS induced COX 2 expression , which is responsible for proinflammatory prostaglandin production , without affecting constitutive COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The objective of this study was to determine the effects of celecoxib , an anti inflammatory / analgesic agent that primarily inhibits COX 2 and not COX 1 at therapeutic doses , on the steady state pharmacokinetic profile and hypoprothrombinemic effect of racemic warfarin in healthy volunteers . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 were expressed in 7 of the 10 cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Arg ( 110 ) , a residue well conserved in the microsomal GSH S transferase family , was essential for catalytic function . mPGES was functionally coupled with COX 2 in marked preference to COX 1 , particularly when the supply of arachidonic acid was limited . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit both cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The specific COX 2 inhibitor , but not the COX 1 inhibitor , decreased mitogenesis and increased gall bladder cell apoptosis as evaluated by the number of floating versus attached cells and the number of floating cells in the terminal phase of apoptosis or dead . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : Prostaglandin synthesis is catalyzed by a constitutive cyclo oxygenase isoform ( COX 1 ) and an inducible isoform ( COX 2 ) . ^^^ It is hypothesized that the analgesic and anti inflammatory effects of nonsteroidal anti inflammatory drugs ( nonspecific COX 1 / COX 2 inhibitors ) such as ibuprofen principally derive from COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because the inhibition of COX 1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection , selective COX 2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Paraffin embedded tissues from 75 patients with urothelial carcinomas were immunostained with specific antibodies raised against COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The number of newly appeared COX 2 ( + ) lymphocytes remained < 50 % that of COX 1 ( + ) cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inducible COX 2 enzyme is responsible for some aspects of pain and inflammation in arthritis while the constitutive COX 1 enzyme appears responsible for most of the gastro protective prostaglandin synthesis in the stomach and duodenum . ^^^ Drugs selective for COX 2 probably act by binding to a pocket in the enzyme that is present in COX 2 but not in COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The pyrrole moiety as a template for COX 1 / COX 2 inhibitors . ^^^ Aroyl and thiophene substituted pyrrole derivatives have been synthesized as a new class of COX 1 / COX 2 inhibitors . ^^^ The inhibition of COX 1 was evaluated in a biological system using bovine PMNLs as the enzyme source , whereas LPS stimulated human monocytes served as the enzyme source for inducible COX 2 . ^^^ The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX 1 and RIA for COX 2 . ^^^ Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To investigate their mechanisms of action , the influence on cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) activities was studied . ^^^ Both OGT and Sanshishi inhibited COX 2 but not COX 1 , this presumably contributing to their suppressive effects on ACF development . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROCEDURE : COX activity was evaluated in the presence and absence of 4 NSAID ( meloxicam , tolfenamic acid , carprofen , and ketoprofen ) , using a canine monocyte / macrophage cell line that constitutively expresses COX 1 , but can be induced to express COX 2 when incubated with lipopolysaccharide . ^^^ Inhibition of prostaglandin E 2 TPGE2 ) synthesis by each NSAID was measured by enzyme immunoassay and attributed to specific COX 1 or COX 2 activity through assessment of COX messenger RNA expression by use of northern blot analysis and reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ The COX selectivity of each drug was evaluated from dose response curves by calculating a ratio ( COX 1 : COX 2 ) of inhibitory concentration values on the basis of concentrations that reduced PGE 2 by 50 % in each COX model . ^^^ RESULTS : Meloxicam and tolfenamic acid preferentially inhibited COX 2 , with meloxicam inhibiting COX 2 activity 12 times more effectively than COX 1 activity . ^^^ Carprofen was only 1 . 75 times more selective for COX 2 than for COX 1 , and ketoprofen was slightly more selective for COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nitric oxide synthase / COX cross talk : nitric oxide activates COX 1 but inhibits COX 2 derived prostaglandin production . ^^^ To separate the activation of phospholipase A 2 and COX , we performed experiments using fibroblasts derived from COX 1 deficient or COX 2 deficient mice . ^^^ Further studies indicated that NO stimulated PGE 2 release in COX 2 deficient cells , without altering COX 1 mRNA or protein expression . ^^^ In contrast , NO inhibited COX 2 derived PGE 2 production in both LPS stimulated macrophages and COX 1 knockout cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In monocytes , cyclooxygenase type 1 ( COX 1 ) activity appears to favor TXA 2 production and COX 2 activity appears to favor PGE 2 production . ^^^ This pattern was observed irrespective of whether PGH 2 was produced by COX 1 or COX 2 or whether it was added directly . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibitory effect of naproxene and its 7 methoxy isomer on constitutive COX 1 and inducible COX 2 . ^^^ We evaluated the ability of naproxene and its 7 methoxy isomer to abrogate constitutive COX 1 and inducible COX 2 activity in human A 549 cells . ^^^ Naproxene inhibited COX 1 ( IC 50 = 3 . 42 microM ) and COX 2 ( IC 50 = 1 . 53 microM ) , whereas the 7 methoxy isomer had no appreciable effect on COX 1 ( IC 50 > > 100 microM ) but also abrogated the activity of COX 2 enzyme ( IC 50 = 14 . 42 microM ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since ten years now , it is well known that this enzyme exists under two forms : a constitutive ( COX 1 ) and an inducible form ( COX 2 ) . ^^^ Observations that COX 1 , involved in several homeostatic processes , played a housekeeping role while COX 2 expression was associated with inflammation and other pathologies such as cancer proliferation have led to the development of COX 2 selective inhibitors in order to reduce the classical side effects , of which gastric irritation is the most common , associated with the use of conventional NSAIDs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase exists in two isoenzymatic forms , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^ Traditional nonspecific NSAIDs inhibit both COX 1 and COX 2 , and in doing so , not only decrease inflammation and pain , but also promote gastrointestinal tract damage and bleeding . ^^^ Recently , a class of anti inflammatory medications has been developed that primarily inhibits COX 2 while sparing the enzymatic activity of COX 1 at therapeutic dosages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX is a key enzyme in prostaglandin biosynthesis , and two isoforms of COX , COX 1 and COX 2 , have been identified . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cPGES / p23 was constitutive and was unaltered by proinflammatory stimuli in various cells and tissues , except that it was increased significantly in rat brain after LPS treatment . cPGES / p23 was functionally linked with COX 1 in marked preference to COX 2 to produce PGE ( 2 ) from exogenous and endogenous arachidonic acid , the latter being supplied by cytosolic phospholipase A ( 2 ) in the immediate response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
HTS and LPS also induced a dose related increase in COX 2 with maximal expression within 4 to 6 hours ; there was no change in COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We used cyclo oxygenase 1 ( COX 1 ) and cyclo oxygenase 2 ( COX 2 ) and 5 lipoxygenase ( 5 LOX ) inhibitors , before the injection of IL 1beta , to explore the role of arachidonic acid metabolic pathways on HPA axis activation . ^^^ Adult male rats were i . m injected 20 min before i . p injection of IL 1beta , with ( 1 ) : a COX 1 / COX 2 inhibitor ( ketoprofen ) ; ( 2 ) a COX 2 selective inhibitor ( NS 398 ) ; or ( 3 ) a 5 LOX inhibitor ( BW A4C ) . ^^^ Administration of the COX 1 / COX 2 inhibitor led to a complete blockage of ACTH and corticosterone secretion and POMC gene transcription . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , traditional nonselective NSAIDs that inhibit COX 1 and COX 2 lead to a state of propensity for gastric and duodenal ulcer disease and ulcer complications . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase ( COX ) enzyme activity in both its constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms were shown also to inhibit the development of colon carcinoma in animal models . ^^^ The expression of COX 1 and COX 2 in prostate tissues from patients with prostate carcinoma was investigated using reverse transcriptase polymerase chain reaction ( RT PCR ) and immunohistochemistry . ^^^ Affinity purified COX 1 and COX 2 antibodies were used in immunochemistry . ^^^ RESULTS : Very weak expression of COX 1 and marked expression of immunoreactive COX 2 in tumor cells was obtained . ^^^ By RT PCR analysis , enhanced expression of COX 2 , but not COX 1 , was observed in PC tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two forms of cyclo oxygenase described are widely different in their location , activity , and role , especially because the COX 1 isoenzyme seems to be mainly a constitutive enzyme whereas the COX 2 isoenzyme is inducible . ^^^ Recent advances have included the development of drugs with a high specificity toward the inducible enzyme ( COX 2 ) to focus on the anti inflammatory actions , because many of the unwanted side effects of NSAIDs have been associated with inhibition of the constitutive isoform ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results emphasise that the appropriate target for NSAID trials in AD is COX 1 , but they also indicate that there would be no contraindication to the use of those traditional NSAIDs which have mixed COX 1 / COX 2 inhibiting activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Levels of constitutive cyclo oxygenase ( COX 1 ) and mitogen inducible cyclo oxygenase ( COX 2 ) in the gastric mucosa were analysed using western blotting and immunohistochemical staining . ^^^ RESULTS : Although there was strong expression of COX 1 , there was minimal expression of COX 2 in the gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 products in the gut : therapeutic impact of COX 2 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our investigation was aimed at a pharmacological comparison of O . bullata and the Cryptocarya species C . latifolia Sonder , C . myrtifolia Stapf . , C . transvaalensis Burtt Davy , C . woodii Engl . and C . wyliei Stapf . , in terms of in vitro cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibition , as an indication of O . bullatas ' repute as a remedy against headache . ^^^ C . woodii bark extracts showed outstanding equipotent activity towards COX 1 and COX 2 . ^^^ Extracts of dried C . wyliei leaves exhibited high inhibitory activity , with a COX 2 / COX 1 ratio of 5 . 8 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : the preventive effect of acetylsalicylic acid in cardiovascular disease may be due to inhibition of platelet aggregation mediated by COX 1 , but may in addition be due to anti inflammatory effects by inhibition of COX 2 . ^^^ The objective of this study was to analyse the expression of COX 1 and COX 2 in atherosclerotic and healthy vascular walls . ^^^ DESIGN : the expression COX 1 and COX 2 was analysed in biopsies from human atherosclerotic carotid arteries and from healthy mammary arteries and saphenous veins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To address this , we analyzed mice lacking COX 1 ( null mutation ) or COX 2 ( pharmacologic inhibition ) or pups with a double null mutation . ^^^ Although patency of the DA is PG dependent , neither COX 1 nor COX 2 expression was detected in the fetal or postnatal DA , and offspring with a double null mutation died shortly after birth with open DAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression did not significantly differ among the groups . ^^^ These results suggest that fish oil derived from tuna , which contains high amounts of DHA and VD 3 , suppresses the formation and growth of ACF without affecting COX 1 and COX 2 expression , and may have a preventive effect on colon carcinogenesis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Reverse transcription polymerase chain reaction was used to measure COX 1 and COX 2 mRNAs in the epididymis in normal and castrated rats . ^^^ In normal rats , COX 1 and COX 2 mRNAs were detected in the intact epididymis . ^^^ Castration caused a time dependent decrease in expression of COX 1 and COX 2 mRNAs , which were partially restored upon testosterone replacement . ^^^ These results suggest that the expression of COX 1 and COX 2 are dependent on androgen . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls , and there was evidence of COX 1 induction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : The immunohistochemical expression of COX 1 , COX 2 and bcl 2 protein was studied using paraffin embedded archival tissues both before and after hormonal therapy . ^^^ RESULTS : Immunohistochemistry for COX 1 , not COX 2 , showed the constitutive expression in the stroma of normal prostate . ^^^ The expression of COX 2 protein was detected less often than that of COX 1 protein in most cases of prostatic adenocarcinoma before hormonal therapy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since selective inhibition of the inducible form of cyclooxygenase ( COX 2 ) might retain all the benefits of classical nonsteroidal antiinflammatory agents while avoiding the major side effects associated with inhibition of the constitutive isoform COX 1 , COX 2 has become an important target for the discovery and development of new antiinflammatory drugs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results suggest that the ulcerogenic potential of preferential a COX 1 inhibitor increases following concomitant administration with a steroid , whereas , nimesulide , a preferential COX 2 inhibitor , is nonulcerogenic , even when administered concomitantly with a steroid , and is therefore a clinically useful antiinflammatory agent . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins formed by cyclooxygenase 1 ( COX 1 ) or COX 2 produce hyperalgesia in sensory nerve endings . ^^^ To assess the relative roles of the two enzymes in pain processing , we compared responses of COX 1 or COX 2 deficient homozygous and heterozygous mice with wild type controls in the hot plate and stretching tests for analgesia . ^^^ In the stretching test , there was less nociception in COX 1 null and COX 1 deficient heterozygotes and also , unexpectedly , in female COX 2 deficient heterozygotes , as shown by a decreased number of writhes . ^^^ Measurements of mRNA levels by reverse transcription PCR demonstrated a compensatory increase of COX 1 mRNA in spinal cords of COX 2 null mice but no increase in COX 2 mRNA in spinal cords of COX 1 null animals . ^^^ Thus , compensation for the absence of COX 1 may not involve increased expression of COX 2 , whereas up regulation of COX 1 in the spinal cord may compensate for the absence of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Many of the structurally diverse indomethacin esters and amides inhibited purified human COX 2 with ICo 5 values in the low nanomolar range but did not inhibit ovine COX 1 activity at concentrations as high as 66 microM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE AND DESIGN : Glomerular expression and localization of the two cyclooxygenase isoforms , Cox 1 and Cox 2 , and the prostaglandin E 2 receptor EP 2 were investigated in a rat model of transient mesangioproliferative glomerulonephritis . ^^^ RESULTS : In normal rat kidney , immunoreactivity of Cox 1 was detected predominantly in collecting duct cells and that of Cox 2 in the macula densa . ^^^ In biopsies of patients with IgA nephritis , predominant expression of Cox 1 , but not Cox 2 , was found in glomeruli , whereas Cox 2 was strongly expressed in infiltrating interstitial cells . ^^^ CONCLUSIONS : The upregulation of glomerular Cox 1 but not Cox 2 and the parallel induction of the EP 2 receptor , which was shown to mediate cAMP accumulation in mesangial cells , suggest that induction of prostaglandin formation may contribute to the resolution rather than to the progression of anti Thy1 . 1 nephritis . ^^^ The expression pattern of Cox 1 and Cox 2 in human IgA nephritis points to a role for both Cox isoforms in human glomerular inflammation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Acetylsalycilic acid , nimesulide , or SQ 22536 was used as respective antagonist of COX 1 , COX 2 , or adenylate cyclase using aortic rings precontracted with phenylephrine and exposed to cumulative concentrations of acetylcholine ( ACh ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In both types of mice induction of thermal hyperalgesia was accompanied by similar increases in COX 1 and COX 2 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin endoperoxide H synthases 1 and 2 ( PGHS 1 and PGHS 2 ; also cyclooxygenases 1 and 2 , COX 1 and COX 2 ) catalyze the committed step in prostaglandin synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cytosolic phospholipase A ( 2 ) ( cPLA ( 2 ) ) plays a key role in the release of arachidonic acid as the substrate of cyclooxygenase 1 ( COX 1 ) or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inhibition of COX 1 and COX 2 enzymes by the curcumins was observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) inhibitors have long been known to attenuate these responses , but recent work has revealed the existence of two distinct isoforms of the enzyme , COX 1 and COX 2 , with different characteristics and functions . ^^^ Therefore , we reassessed the COX involvement using inhibitors with different selectivities for COX 1 and COX 2 . ^^^ Pretreatment of the mice with aspirin , an irreversible inhibitor of COX 1 and COX 2 , prevented the hypophagic response to IL 1 , 16 h , but not 40 h later . ^^^ Taken together , these results suggest that COX 1 may be the major isozyme involved in the hypophagic responses to LPS and IL 1 , but a role for COX 2 can not be excluded . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists in two isoforms , COX 1 is the constitutive whereas COX 2 is the inducible isoform . ^^^ The regulation of COX 1 and COX 2 expression in nasal mucosa has not been previously reported . ^^^ AIM : We studied expression and regulation by cytokines and corticosteroids of COX 1 and COX 2 in human nasal mucosa . ^^^ Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for COX 1 and COX 2 expression by semiquantitative competitive PCR and Western blot . ^^^ RESULTS : The baseline expression of COX 2 mRNA was higher than COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of this study was to assess the selectivity and potency of the nonsteroidal anti inflammatory drug ( NSAID ) , flurbiprofen , and its enantiomers in their inhibition of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^ Incubation with E . coli lipopolysaccharide ( LPS ) during 24 hr produced prostaglandin E 2 ( PGE 2 ) by induction of COX 2 in monocytes , suppressing any possible contribution of COX 1 activity by the addition of acetylsalicylic acid . ^^^ R ( ) flurbiprofen , expressed as the reciprocal of the ratio of the concentrations giving 50 % inhibition ( IC 50 ) , is 340 for COX 1 and 56 for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of the present study was to characterize the isoforms of cyclooxygenase ( COX ) in the human iris before and after stimulation with lipopolysaccharide ( LPS ) and to determine the selectivity of the nonsteroidal anti inflammatory drug ( NSAID ) , S ( + ) flurbiprofen , for inhibition of COX 1 and COX 2 in homogenates of this tissue . ^^^ After reacting with anti COX 1 and anti COX 2 immunoglobulin G , the presence of both immunoreactive COX enzymes was substantiated using an indirect immunoperoxidase method . ^^^ Authentic COX 1 and COX 2 were used as controls . ^^^ The selectivity of S ( + ) flurbiprofen for inhibition of COX 1 was expressed as the ratio of IC 50 for COX 2 / COX 1 . ^^^ After incubation with LPS plus acetylsalicylic acid , positive staining was observed for both COX 1 ir and COX 2 ir . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : SC 560 markedly reduced gastric prostaglandin synthesis and platelet COX 1 activity , but spared COX 2 and did not cause gastric damage . ^^^ CONCLUSIONS : Inhibition of both COX 1 and COX 2 is required for NSAID induced gastric injury in the rat . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The compound isolated from this extract , 7 hydroxy 3 , 4 dihydrocadalin , showed anti inflammatory effect on the same experimental model ( ED 50 of 0 . 9 mumol / ear ) , as well as on COX 1 and COX 2 catalysed prostaglandin biosynthesis assays , with IC 50 values of 22 microM and 526 microM , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) are known , and to date most studies have implicated COX 2 , rather than COX 1 , as the isoform involved in colon carcinogenesis . ^^^ In the present study , we show that homologous disruption of either Ptgs 1 or Ptgs 2 ( genes coding for COX 1 or COX 2 , respectively ) reduced polyp formation in Min / + mice by approximately 80 % . ^^^ Only COX 1 protein was immunohistochemically detected in normal intestinal tissue , whereas both COX 1 and variable levels of COX 2 protein were detected in polyps . ^^^ Prostaglandin E 2 was increased in polyps compared with normal tissue , and both COX 1 and COX 2 contributed to the PGE 2 produced . ^^^ The results indicate that COX 1 , as well as COX 2 , plays a key role in intestinal tumorigenesis and that COX 1 may also be a chemotherapeutic target for nonsteroidal anti inflammatory drugs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Colon tumors were analyzed for iNOS , COX 1 , and COX 2 expression and enzymatic activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present results showed the differential expression of basal Cox 1 and Cox 2 mRNA in the rat tissues , suggesting that Cox 1 and Cox 2 may contribute to the regulation of normal pathophysiological conditions in a tissue specific manner . ^^^ Thus , it is desirable to perform mapping of the basal expression of Cox 1 and Cox 2 in specific organs in the body in order to anticipate the effects of non steroidal anti inflammatory drugs on normal pathophysiological conditions . ^^^ Finally , no difference was observed between F 344 and BN rat tissues in the levels of Cox 1 and Cox 2 mRNA expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of Cox have been identified , Cox 1 ( constitutively expressed ) and Cox 2 ( inducible form ) , which are the products of two different genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two NSAIDs ( celecoxib and rofecoxib ) with very high specificity for COX 2 and virtually no activity against COX 1 at therapeutic doses have been approved for clinical use . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The three esophageal adenocarcinoma cell lines , Flo 1 , Bic 1 , and Seg 1 , also demonstrated varying expression patterns for COX 1 and COX 2 . ^^^ In Flo 1 cells , which expressed almost undetectable levels of COX 1 and COX 2 , and in Seg 1 , which expressed significant levels of COX 1 and COX 2 , indomethacin caused upregulation of the pro apoptotic protein Bax . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 was detected in both normal and H . pylori infected mucosa , whereas COX 2 was expressed only in the infected mucosa . ^^^ These results indicate that COX 2 as well as COX 1 might play anti inflammatory roles in H . pylori induced gastritis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , prostaglandin synthetic enzymes , COX 1 and COX 2 , were not found to be induced by androgens . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase exists in two isoforms ( COX 1 and COX 2 ) . ^^^ It has been proposed that NSAIDs with preferential COX 2 selectivity have fewer renal side effects than drugs with preferential COX 1 selectivity . ^^^ Etodolac is a relative selective inhibitor of COX 2 , while ibuprofen has a higher potency against COX 1 than COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : To determine the cell specific expression of the two major isoforms of cyclooxygenase ( COX 1 and COX 2 ) in human noncancerous and cancerous prostatic tissues . ^^^ METHODS : Thirty one specimens of prostate carcinoma ( CaP ) and 10 specimens of benign prostatic hyperplasia ( BPH ) were stained with mouse antihuman COX 1 and COX 2 monoclonal antibodies . ^^^ CONCLUSIONS : The results of the present study indicate that expression of both COX 1 and COX 2 in human CaP is increased . ^^^ These data indicate that COX 1 and COX 2 ( and / or their prostaglandin products ) may play a role in the malignant transformation of the prostate . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In a series of trials , young ( 3 to 5 wk of age ) cockerels infected with Eimeria acervulina , a duodenal parasite , received oral treatments with indomethacin ( IM ) , an inhibitor of both COX 1 and COX 2 , or nimesulide ( NIM ) , a specific inhibitor of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX has two isoforms : COX 1 , the constitutively expressed form , and COX 2 , the inducible form . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Comparative inhibitory activity of rofecoxib , meloxicam , diclofenac , ibuprofen , and naproxen on COX 2 versus COX 1 in healthy volunteers . ^^^ Steady state inhibitory activity of rofecoxib ( Vioxx ) on COX 2 versus COX 1 was compared with that of commonly used nonsteroidal anti inflammatory drugs ( NSAIDs ) in 76 healthy volunteers randomized to placebo , rofecoxib 12 . 5 mg qd , rofecoxib 25 mg qd , diclofenac 50 mg tid , ibuprofen 800 mg tid , sodium naproxen 550 mg bid , or meloxicam 15 mg qd . ^^^ Ex vivo whole blood assays were used to determine the effect on COX 2 and COX 1 activity , respectively . ^^^ These data support the contention that rofecoxib is the only drug of the regimens tested that uniquely inhibits COX 2 without affecting COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 or COX 2 knockout mice may provide many clues on the roles of COX 2 , but may simultaneously cause unnecessary confusion in the recognition of the roles of COX 2 , and this is discussed . ^^^ Because of the short duration of the expression of COX 2 gene and protein , COX 2 must play some roles different from those of COX 1 gene and protein in vivo . ^^^ It is not yet possible to identify all the roles of COX 2 , but in some tissues , such as the kidney , the brain and others , COX 2 may be expressed constitutively , whereas the prostaglandin generation by COX 2 may replace that by COX 1 in some states ( or vice versa ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In young rats , acetylcholine ( ACh ) caused a complete relaxation which was not affected by indomethacin ( 0 . 3 microM ) , NS 398 ( a preferential COX 2 inhibitor ; 1 microM ) , SQ 29548 ( a thromboxane receptor antagonist ; 1 microM ) , nor valeryl salicylate ( VAS , a preferential inhibitor of COX 1 ; 3 mM ) . ^^^ Aortic endothelial cells from aged but not young rats express COX 2 isoform , while COX 1 labelling was observed in endothelial cells from both young and aged rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase isoforms have been identified and are referred to as COX 1 and COX 2 . ^^^ COX 1 enzyme is constitutively expressed and regulates a number of housekeeping functions such as vascular hemostasis and gastroprotection , whereas COX 2 is inducible ( i . e . , sites of inflammation ) by number of mediators such as growth factors , cytokines and endotoxins . ^^^ Beneficial effects are due to inhibition of COX 2 and detrimental effects are due to inhibition of physiological COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All conventional NSAID inhibit both cyclooxygenase 1 ( COX 1 ) and COX 2 enzymes . ^^^ As COX 1 is constitutively expressed in many tissues and contributes to the maintenance of the normal physiologic state in the GI tract , the kidney , and platelets , an agent that specifically inhibits COX 2 , an inducible enzyme associated with the inflammatory response , would be highly desirable . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Arachidonic acid metabolism is governed by 2 isoforms of cyclooxygenase ( COX ) , the constitutively expressed COX 1 and the inducible COX 2 . ^^^ Antiinflammatory , analgesic , and antipyretic effects of nonsteroidal antiinflammatory drugs ( NSAID ) are explained by the capacity of these agents to inhibit COX 2 , whereas the serious gastrointestinal side effects are caused by inhibitors of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This new knowledge led to the development of drugs that are highly specific inhibitors of COX 2 while not inhibiting COX 1 at maximally efficacious dosages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This knowledge has led to the development of new compounds that , at therapeutic concentrations , inhibit COX 2 without affecting COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Renal prostaglandin ( PG ) synthesis is mediated by cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) . ^^^ The present studies were designed to examine the potential link between medullary COX 1 and COX 2 expression in hypertonic stress . ^^^ In response to water deprivation , COX 2 , but not COX 1 , mRNA levels increase significantly in the renal medulla , specifically in renal medullary interstitial cells ( RMICs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two COX isoenzymes , COX 1 and COX 2 , and the detection of their separate function and regulation , has initiated the search for new and putatively more selective inhibitors of prostaglandin biosynthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs ( NSAIDs ) have as their common mechanism the inhibition of cyclooxygenase ( COX ) enzymes , of which two isoforms ( COX 1 and COX 2 ) exist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This review will focus on the differences in the structure of the COX 1 and COX 2 molecules , particularly the active site and how they are bound by various NSAIDs to achieve COX 2 selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immature MDC ( 1 MDC ) and mature MDC express COX 1 , but , unlike monocytes , both MDC populations constitutively express COX 2 . ^^^ COX 2 is functional in MDC as a specific inhibitor , NS 398 , significantly reduces PGE ( 2 ) production . 1 MDC undergoing maturation with soluble CD 40 ligand ( sCD40L ) increase PGE ( 2 ) synthesis , but prostanoid synthesis is switched to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX enzyme exists in 2 isoforms , COX 1 and COX 2 . ^^^ COX 1 enzyme is thought to mediate `` housekeeping ' ' or homeostatic functions , and COX 2 is considered an inducible enzyme in response to injury or inflammation . ^^^ COX 2 inhibitors are the `` next generation ' ' NSAIDs that may selectively block the COX 2 isoenzyme without affecting COX 1 function . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gastrointestinal tolerability of the selective cyclooxygenase 2 ( COX 2 ) inhibitor rofecoxib compared with nonselective COX 1 and COX 2 inhibitors in osteoarthritis . ^^^ BACKGROUND : Most nonsteroidal anti inflammatory drugs ( NSAIDs ) are nonselective cyclooxygenase ( COX 1 and COX 2 ) inhibitors and are associated with a variety of upper gastrointestinal ( GI ) tract symptoms . ^^^ The roles of COX 1 and COX 2 in the pathogenesis of these symptoms are unclear . ^^^ To test whether COX 2 inhibition with rofecoxib would have greater GI tolerability than nonselective COX 1 and COX 2 inhibition , we compared the incidences of ( 1 ) treatment discontinuations for GI adverse events ( AEs ) and ( 2 ) prespecified dyspeptic type GI AEs among patients with osteoarthritis treated with rofecoxib vs NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At the beginning of the 90 ties it became evident , that cyclooxygenase existed in two isoforms ( COX 1 and COX 2 ) . ^^^ A new NSAID , rofecoxib , has selective COX 2 inhibition defined as inhibition of COX 2 , but not COX 1 in the therapeutic dose range . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of constitutive cyclooxygenase ( COX 1 ) and COX 2 in gastric mucosa was determined using Western blot analysis . ^^^ COX 2 expression was enhanced , whereas COX 1 expression did not change significantly in the gastric mucosa of rats after treatment with rebamipide . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NS 398 and indomethacin did not affect protein levels of COX 1 and COX 2 but dexamethasone significantly reduced the level of COX 2 in granulation tissue at day 6 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synthesis of prostaglandins is catalyzed by either of two cyclooxygenase isoforms , Cox 1 and Cox 2 . ^^^ To determine directly whether prostaglandins synthesized by Cox 1 or Cox 2 regulate crypt epithelial cell fate after genotoxic or cytotoxic injury , we examined apoptosis , prostaglandin synthesis , and crypt stem cell survival after gamma irradiation in Cox 1 ( / ) and Cox 2 ( / ) mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin series of bioactive compounds is formed by the interaction of two distinct but related enzymes , cyclo oxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) . ^^^ The two recently developed and clinically available selective COX 2 inhibitors , celecoxib and rofecoxib , are about 100 1000 times more selective on the COX 2 than on the COX 1 isoform . ^^^ The major clinical interest of these drugs has been related to the lower incidence of gastrointestinal bleeding which , with the conventional COX 1 / COX 2 agents has been a source of hospitalisation , disablement and death , especially in the elderly . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mammalian cells contain two related but unique isoforms of cyclooxygenase ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression in adenocarcinoma cell lines was determined using reverse transcription PCR and Western blotting for mRNA and protein , respectively . ^^^ Esophageal adenocarcinoma cell lines were treated with various concentrations of NS 398 ( selective for COX 2 inhibition ) and flurbiprofen ( selective for COX 1 inhibition ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , outcome clinical studies are needed to compare the adjuvant anti ulcer therapies given with COX 1 inhibitors versus the selective COX 2 inhibitors given alone . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , a specific COX 2 inhibitor , Celecoxib , was developed , which inhibits COX 2 induced inflammation without inhibiting the cytoprotective function of cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We report data from two related assay systems ( isolated enzyme assays and whole blood assays ) that C phycocyanin a biliprotein from Spirulina platensis is a selective inhibitor of cyclooxygenase 2 ( COX 2 ) with a very low IC ( 50 ) COX 2 / IC ( 50 ) COX 1 ratio ( 0 . 04 ) . ^^^ The extent of inhibition depends on the period of preincubation of phycocyanin with COX 2 , but without any effect on the period of preincubation with COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam ( preferential COX 2 inhibitor ) inhibits the growth of COX 2 positive and COX 1 negative colorectal cancer cells . ^^^ By reverse transcriptase polymerase chain reaction ( RT PCR ) and Western blot analysis , COX 2 but not COX 1 was expressed in human non small cell lung cancer ( NSCLC ) cell lines ( A 549 and PC 14 ) . ^^^ In human small cell lung cancer ( SCLC ) cell line ( H 841 ) , both COX 1 and COX 2 were not detected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent studies have revealed the existence of 2 isozymes of cyclooxygenase ( COX ) , called COX 1 and COX 2 . ^^^ The purpose of the present study was to investigate the contribution of COX 1 and COX 2 to PGE 2 production by human peripheral blood monocytes that are stimulated with lipopolysaccharides ( LPS ) from periodontopathogenic bacteria . ^^^ Expression of COX 1 and 2 proteins was studied by immunocytochemical staining , and COX 2 mRNA expression was examined by Northern blot analysis . ^^^ Indomethacin , a non selective COX 1 / COX 2 inhibitor , and NS 398 , a specific COX 2 inhibitor , completely inhibited PGE 2 production . ^^^ Immunocytochemical staining of COX 1 and COX 2 proteins showed that expression of COX 2 protein was increased in monocytes that were stimulated with A . actinomycetemcomitans or P . gingivalis LPS , compared with that in unstimulated monocytes , whereas expression of COX 1 protein was not altered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results were supported by immunoblotting , which showed similar levels of COX 1 in both BPH and cancer , but four times greater expression of COX 2 in cancer than in BPH . ^^^ CONCLUSION : This is the first study to assess the co expression of COX 1 and COX 2 proteins in benign and malignant human prostates , and showed the induction and significantly greater expression of COX 2 in cancer , which was also associated with tumour grade . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE ( 2 ) production increased over 24 h and was accompanied by an increase in cyclooxygenase 2 ( COX 2 ) expression , while COX 1 expression remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Interestingly , only COX 2 protein , but not COX 1 protein , was induced in 17beta estradiol treated HUVEC and was also inhibited by staurosporine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We therefore investigated COX 1 and COX 2 expression , localisation , and activity in normal and abnormal human gastric mucosa . ^^^ METHODS : COX 1 and COX 2 distribution was investigated by light and electron microscopic immunohistochemistry and by western blot analysis , and their contribution to prostaglandin ( PG ) E ( 2 ) synthesis using selective enzyme inhibitors . ^^^ RESULTS : There was strong parietal cell COX 1 and COX 2 immunoreactivity in all sections and isolated cells , with macrophage and myofibroblast reactivity in some sections . ^^^ COX 1 and COX 2 immunostaining was increased in Helicobacter pylori gastritis , particularly the mid glandular zone and lamina propria inflammatory cells . ^^^ This was associated with increased ex vivo PGE ( 2 ) synthesis ( 62 . 4 ( 13 . 5 ) pg / mg 5 36 . 3 ( 15 . 5 ) pg / mg in uninflamed mucosa ; p=0 . 017 ) which was significantly inhibited by COX 1 but not COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several types of human tumors overexpress cyclooxygenase ( COX ) 2 but not COX 1 , and gene knockout transfection experiments demonstrate a central role of COX 2 in experimental tumorigenesis . ^^^ In contrast , aspirin like nonselective NSAIDs such as sulindac and indomethacin inhibit not only the enzymatic action of the highly inducible , proinflammatory COX 2 but the constitutively expressed , cytoprotective COX 1 as well . ^^^ Selective COX 2 inhibitors , such as meloxicam , celecoxib ( SC 58635 ) , and rofecoxib ( MK 0966 ) , are NSAIDs that have been modified chemically to preferentially inhibit COX 2 but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Some of the NSAID induced gastric ulceration and bleeding will most likely be avoided by adopting the use of cyclooxygenase 2 ( COX 2 ) selective NSAIDs , which will selectively inhibit COX 2 while sparing COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Arachidonic acid ( AA ) released by cPLA ( 2 ) and sPLA ( 2 ) s is supplied to both COX 1 and COX 2 in the immediate , and predominantly to COX 2 in the delayed , PG biosynthetic responses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nimesulide ( 3 mg / kg ) , another selective COX 2 inhibitor , however , never affected this increase , suggesting that the gastric PGE ( 2 ) may be produced via COX 1 . ^^^ These results suggest that the potent anti inflammatory effect of meloxicam , accompanied with low gastric toxicity , may be related to its relative selectivity for COX 2 over COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One major finding was that two distinct cyclooxygenase ( COX 1 and COX 2 ) enzymes exist in the kidney . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
With the discovery of cyclo oxygenase isoforms ( Cox 1 and Cox 2 ) , preferential and specific Cox 2 inhibitors have been developed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX 2 vs COX 1 inhibitors ( IC ( 50 ) = 0 . 6 100 nM for COX 2 , 100 > 1000 nM for COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After 4 h of stimulation , IL 1beta induced gene expression of cyclooxygenase 2 ( COX 2 ) but not cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because the prostanoids produced by COX 1 appear to play a physiological role ( protection of the gastric mucosa , platelet aggregation , vascular homeostasis , maintenance of renal sodium water balance ) while those produced by COX 2 seem mainly to intervene in the inflammatory response and in certain processes associated with cell proliferation , the hypothesis has been put forward that the NSAIDs that are selective COX 2 inhibitors should theoretically be capable of maintaining NSAID therapeutic properties but also have fewer adverse side effects due to the maintenance of prostaglandin production at normal physiological levels . ^^^ CURRENT KNOWLEDGE AND KEY POINTS : The hypothesis of COX isoenzyme selectivity has led to a proposed classification for COX inhibitors : 1 ) COX 1 selective inhibitors ( low dosage aspirin ) ; 2 ) COX non selective inhibitors ( the majority of classified NSAIDs , which when administered over the long term , e . g . , in cases of rheumatoid arthritis , cause duodenal ulcers in 20 % of cases and gastric hemorrhage in 1 4 % of cases / year ) ; 3 ) COX 2 preferential inhibitors ( meloxicam and nimesulide , which have fewer gastric side effects than standard NSAIDs , but which are not risk free at high doses ) ; 4 ) COX 2 selective inhibitors ( celecoxib and rofecoxib ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using a quantitative reverse transcription polymerase chain reaction ( RT PCR ) assay to measure the contents of mRNAs we found 3h after kainate injection ( intraperitoneally ; 10 mg / kg ) increased mRNA levels of 5LOX and COX 2 , but not that of COX 1 in the hippocampus of rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Cellular localisation of the cyclooxygenase ( COX ) isozymes COX 1 and COX 2 was analysed in 24 cholangiocarcinomas , including 17 matched tissues originating from non tumorous liver tissue adjacent to tumours and seven biopsies of normal human liver , by immunohistochemistry using isozyme selective antibodies . ^^^ CONCLUSION : Aberrant COX 2 expression occurs during the early stage while COX 1 over expression seems to be related to later stages of cholangiocarcinogenesis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 generates prostaglandins with physiological functions , COX 2 is induced by inflammation and its physiologic functions are unclear at present . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since the constitutive COX 1 enzyme was identified as responsible for gastroprotection and inhibition of platelet function , the potential for compounds that were both effective and safer than NSAIDs led to rapid development of agents that specifically inhibit COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two COX isoenzymes , a constitutive COX 1 , serving homeostatic prostanoid synthesis , and an inducible COX 2 , responsible for proinflammatory prosta noid production , led to the development of new NSAIDs : Preferential and specific COX 2 inhibitors , promising minimal NSAID typical toxicity with equivalent efficacy . ^^^ However , we learned that there is no clear distinction in `` physiologic ' ' constitutive COX 1 and `` inflammatory ' ' inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two COX iso enzymes have been associated with brain disease , the constitutively expressed COX 1 and the cytokine inducible COX 2 . ^^^ We have used single and double labeling immunohistochemistry to analyse COX 1 and COX 2 expression in twenty six primary WHO grade 2 oligodendrogliomas , sixteen primary WHO grade 3 anaplastic oligodendrogliomas , twenty seven matched recurrences and ten neuropathologically unaltered brains . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Labial salivary gland tissue samples were analysed immunohistochemically using anti COX 1 and COX 2 antibodies . ^^^ In contrast to COX 1 staining , only a little COX 2 immunostaining was observed in salivary gland tissues from SS patients . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Based on an in vitro whole blood assay , none of the known human metabolites of rofecoxib inhibits COX 1 nor contributes significantly to the inhibition of COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Following northern blot analysis , canine platelets were found to express only the 2 . 8 kb COX 1 transcript ; COX 2 was not detected . ^^^ Canine MDCK cells expressed the 4 . 5 kb COX 2 transcript , in addition to the 2 . 8 kb COX 1 transcript . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The generation of PGs from arachidonic acid is mediated by cyclooxygenase ( COX ) , which consists of a constitutive ( COX 1 ) and an inducible ( COX 2 ) isoform . ^^^ The present study evaluated the relative expression and immunoreactive levels of COX 1 and COX 2 , by means of RT PCR , Western blot analysis , and immunohistochemistry , in the renal cortex and medulla of rats with congestive heart failure ( CHF ) , induced by the placement of an aortocaval fistula . ^^^ In addition , we examined the effects of a COX 1 inhibitor ( piroxicam ) , COX 2 inhibitor ( nimesulide ) , and nonselective COX inhibitor ( indomethacin ) at a dose of 5 mg / kg , on intrarenal blood flow by laser Doppler flowmetry . ^^^ COX 1 and COX 2 mRNAs were abundantly expressed in the renal medulla of control and CHF rats and only minimally in the cortex . ^^^ Moreover , both RT PCR ( 32 36 cycles ) and Western blot techniques revealed upregulation of medullary COX 2 , but not of COX 1 , in rats with advanced heart failure . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In parallel , there was a threefold increase of renocortical COX 2 abundance , while the COX 1 mRNA level remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : We used an in vitro approach to examine the expression of COX 1 and COX 2 and the production of TXA 2 in response to fragments of HA . ^^^ RESULTS : In TECs and MPhis , HA increased the steady state COX 2 mRNA and protein levels markedly , whereas COX 1 mRNA levels did not change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : COX 2 expression is upregulated in well and moderately differentiated carcinomas of the lung , colon , and breast whereas COX 1 appears to be constitutively expressed at low levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cellular localization of COX 1 and COX 2 were determined by immunohistochemistry and double immunofluorescence . ^^^ At the ulcer edge , COX 1 was significantly increased in lamina propria cells whereas COX 2 was strongly expressed in the hyperplastic foveolar epithelium in H . pylori and non steroidal anti inflammatory drugs ( NSAID ) associated ulcers . ^^^ At the ulcer base , there was strong expression of COX 1 and COX 2 in myofibroblasts , macrophages and endothelial cells in the granulation tissue , irrespective of H . pylori status or NSAID use . ^^^ Messenger RNA of COX 1 and COX 2 were demonstrated by reverse transcription polymerase chain reaction . ^^^ CONCLUSION : Both COX 1 and COX 2 are up regulated in human gastric ulcers . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This enzyme exists in two isoforms , COX 1 and COX 2 . ^^^ Inhibition of COX 1 is thought to be the main cause of the gastrointestinal unwanted effects of NSAIDs , whilst inhibition of COX 2 results in anti inflammatory effects . [ symbol : see text ] Rofecoxib ( Vioxx MSD ) and [ symbol : see text ] celecoxib ( Celebrex Searle ) have been developed as selective inhibitors of COX 2 . ^^^ The manufacturer claims that `` in clinical studies rofecoxib inhibits COX 2 but not COX 1 ' ' , has `` the power of high dose NSAIDs diclofenac and ibuprofen ' ' and `` superior GI safety profile compared to conventional NSAIDs ' ' . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGs are produced by the action of cyclooxygenase ( COX ) enzymes , and two forms of COX , COX 1 and COX 2 , have been described . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the effects of cyclooxygenase 1 ( COX 1 ) and COX 2 gene deletion on collagen induced arthritis ( CIA ) . ^^^ METHODS : Mice that were susceptible to CIA but lacked either the COX 1 or the COX 2 gene were immunized with type 2 collagen ( CII ) , and the incidence and severity of arthritis were compared with findings in wild type animals , by clinical and histologic examination . ^^^ RESULTS : COX 2 gene deletion reduced the incidence and severity of CIA compared with findings in wild type and COX 1 / mice . ^^^ Histologic examination of joints after the onset of clinical arthritis revealed cartilage erosions , proliferation of the synovial lining , and inflammatory cell infiltration in wild type and COX 1 / mice , but not in COX 2 / mice . ^^^ However , cytokine production by spleen cells from immunized mice indicated no cytokine deficiencies in COX 2 / mice compared with wild type or COX 1 / mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs exert their anti inflammatory effects by inhibiting the activity of the COX enzyme , which was recently shown to exist in two isoforms , a constitutive COX 1 and an inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIM : To evaluate the expression of COX 1 and COX 2 in H . pylori gastritis at messenger RNA ( mRNA ) and protein levels . ^^^ The levels of COX 1 and COX 2 mRNA were compared between H . pylori infected and uninfected specimens using reverse transcription polymerase chain reaction . ^^^ RESULTS : A total of 40 H . pylori infected and 40 uninfected specimens were studied . mRNA of COX 2 but not COX 1 was elevated in H . pylori infected mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas many of the side effects of NSAIDs ( e . g . gastrointestinal ulceration and bleeding , platelet dysfunctions ) are due to a suppression of COX 1 activity , inhibition of COX 2 derived prostanoids facilitates the anti inflammatory , analgesic and antipyretic effects of NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The genes encoding Cox 1 , Cox 2 , Cox 3 , Cob , Atp 6 , Atp 8 , Atp 9 , several subunits of the NADH dehydrogenase complex 1 and 11 tRNAs were unambiguously identified . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Key enzyme in this process is cyclooxygenase occurring in two isoforms : COX 1 and COX 2 . ^^^ Antiinflammatory effect of NSAIDs is mediated by COX 2 inhibition , while the side effects ( gastrotoxicity , nephrotoxicity ) by inhibition of COX 1 . ^^^ COX 1 was more inhibited by indomethacin and piroxicam and COX 2 by 6 MNA ( active metabolite of nabumetone ) , diclofenac and ibuprofen . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We explored a panel of genes that may affect metastatic propensity , namely , metalloproteinase 9 ( MMP 9 ) , tissue inhibitor of metalloproteinase 2 ( TIMP 2 ) , cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) , and vascular endothelial growth factor ( VEGF ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The selective COX 2 inhibitor , nimesulide , but not the COX 1 inhibitor valeryl salicylate , significantly attenuated SLIGRL NH ( 2 ) induced smooth muscle relaxation and PGE ( 2 ) release . 6 . ^^^ PAR stimulated PGE ( 2 ) release appears to be generated preferentially by COX 2 rather than COX 1 , and induces relaxation via activation of the EP ( 2 ) receptor . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we have examined the relative importance of cyclo oxygenase 1 ( COX 1 ) and cyclo oxygenase 2 ( COX 2 ) for PGE ( 2 ) formation in the foetal lamb ductus ( 0 . 65 gestation onwards ) . 2 . ^^^ Using fluorescence microscopy and immunogold staining , COX 1 appeared more abundant than COX 2 in endothelial and smooth muscle cells , and this difference was greater before term . ^^^ Inside muscle cells , COX 1 and COX 2 immunoreactivity was located primarily in the perinuclear region . ^^^ COX 1 immunoreactivity remained virtually unchanged with either treatment ; however , this isoform as well as any induced COX 2 migrated towards the outer cytoplasm . 3 . ^^^ We conclude that COX 1 and COX 2 develop unevenly in the ductus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Additionally , reverse transcription polymerase chain reaction and immunoblotting determined that the mRNA and protein levels of the eicosanoid forming enzymes cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , and PGI synthase were not significantly changed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of the cyclooxygenase isoenzymes COX 1 and COX 2 provide neuroprotection in the MPTP mouse model of Parkinson ' s disease . ^^^ To study the possible role of the isoenzymes of cyclooxygenase COX 1 and COX 2 in the MPTP ( 1 methyl 4 phenyl 1 , 2 , 3 , 6 tetrahydropyridine ) mouse model of Parkinson ' s disease we used acetylsalicylic acid , a COX 1 / COX 2 inhibitor , in comparison with meloxicam , a preferential COX 2 inhibitor . ^^^ In conclusion , the inhibition of either COX 1 / COX 2 by acetylsalicylic acid or preferentially COX 2 by meloxicam provided a clear neuroprotection against MPTP toxicity on the striatal and nigral levels . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX has two isoforms : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It inhibits both COX 1 and COX 2 weakly in vitro , but reduces prostaglandin synthesis markedly in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : Since gastrin is recognized as a effective gastric mitogen , it could be capable to induce COX 2 , a potent tumor growth promoting and angiogenic factor , we decided 1 ) to compare the seroprevalence of HP and its cytotoxic protein , CagA , in gastric cancer patients with those in age and gender matched controls ; 2 ) to determine the gene expression of gastrin and its receptors ( CCK ( B ) R ) in gastric cancer , 3 ) to assess the plasma levels , gastric lumen and tumor tissue contents of gastrin and 4 ) to examine the mRNA and enzyme protein expression of COX 1 and COX 2 in cancer tissue and intact gastric mucosa before and after HP eradication . ^^^ Gene expressions of gastrin , CCK ( B ) R , COX 1 and COX 2 was examined using RT PCR with GAPDH as a reference and employing Western blot for COX 2 expression , while gastrin was measured by RIA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Ulcer healing involves expression of various growth factors including hepatocyte growth factor ( HGF ) at the ulcer margin and the rise in plasma gastrin but the effects of locally applied HGF and gastrin , which are known to act as trophic factors for the gastric mucosa , with or without neutralizing antibodies against HGF and gastrin or COX 1 and COX 2 inhibitors on ulcer healing and the expression of cyclooxygenase ( COX ) 1 and COX 2 during this healing have been little studied . ^^^ At day 13 and 21 , the area of ulcers was determined by planimetry , the gastric blood flow ( GBF ) at ulcer margin was examined by H 2 gas clearance technique and mucosal generation of PGE 2 and the expression of COX 1 and COX 2 mRNA in the non ulcerated and ulcerated gastric mucosa was analyzed using RT PCR . ^^^ Treatment with HGF and gastrin significantly accelerated the rate of ulcer healing and raised GBF at ulcer margin causing further significant upregulation of COX 2 mRNA and COX 2 protein ( but not of COX 1 mRNA ) in the ulcerated mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , COX was elucidated to consist of 2 types of isoform , a constitutive form of COX 1 and an inducible form of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Constitutive expression of COX 1 but also of COX 2 mRNA was found in mucosal scrapings of the rat jejunum . ^^^ Cholera toxin had no effect on COX 1 as well as COX 2 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study the expression of COX 1 and COX 2 in AD and non demented control temporal and frontal cortex was investigated using immunohistochemistry . ^^^ COX 1 expression was detected in microglial cells , while COX 2 expression was found in neuronal cells . ^^^ In AD brains , COX 1 positive microglial cells were primarily associated with amyloid beta plaques , while the number of COX 2 positive neurons was increased compared to that in control brains . ^^^ Although astrocytes are used in studies in vitro to investigate the role of COX in AD , there are no indications that these cells express COX 1 or COX 2 in vivo . ^^^ The different distribution patterns of COX 1 and COX 2 in AD could implicate that these enzymes are involved in different cellular processes in the pathogenesis of AD . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase exist , designated COX 1 and COX 2 . ^^^ COX 1 predominates in vascular smooth muscle and collecting ducts , whereas COX 2 predominates in the macula densa and nearby cells in the cortical thick ascending limb . ^^^ Whereas COX 1 expression does not exhibit dynamic regulation , COX 2 expression is subject to regulation by several environmental conditions , including salt intake , water intake , medullary tonicity , growth factors , cytokines , and adrenal steroids . ^^^ Many of the renal effects of non selective non steroidal anti inflammatory drugs ( including sodium retention , decreased glomerular filtration rate , and effects on renin angiotensin levels ) appear to be mediated by the inhibition of COX 2 rather than COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The NSAIDs used in this study include acetylsalicylic acid ( ASA ) that is anti inflammatory with COX 1 and COX 2 inhibition and N [ 2 ( cyclohexyloxy ) 4 nitrophenyl ] methanesulfonamide ( NS 398 ) that is a specific COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 derived PGs are thought to mediate cytoprotective actions on the gastrointestinal mucosa , whereas COX 2 derived PGs are assumed to display pro inflammatory properties . ^^^ This review will focus on the roles of COX 1 and COX 2 in inflammation , based on studies involving pharmacologic COX inhibitors as well as COX knock out mice , with a particular emphasis on the gastrointestinal tract . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NS 398 , a specific COX 2 inhibitor , completely inhibited PGE 2 production by IL 1beta stimulated HGF , as did indomethacin , a COX 1 / COX 2 inhibitor . ^^^ Northern blot analysis and immunocytochemical staining showed that mRNA and protein of COX 2 were expressed in IL 1beta challenged HGF , but not in unstimulated HGF , and that the expression of mRNA and protein of COX 1 was similar both in unstimulated and in stimulated cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are 2 isoforms of cyclooxygenase : COX 1 , which constitutively produces prostaglandins and COX 2 , which is induced by inflammation . ^^^ We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins , whereas the selective COX 2 inhibitor , etodolac , would permit repair as a result of continued COX 1 prostaglandin production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gene expression of gastrin , CCKB R , COX 1 and COX 2 was examined using RT PCR , while gastrin was measured by specific RIA . ^^^ Both gastrin and CCKB R mRNA were detected in the cancer tissue and at the resection margin and similarly COX 2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX 1 was found . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We studied whether NS 398 , a selective cyclo oxygenase 2 ( COX 2 ) enzyme inhibitor , and piroxicam , an inhibitor of COX 2 and the constitutively expressed COX 1 , protect neurones against hypoxia / reoxygenation injury . ^^^ Western blotting revealed no COX 1 or COX 2 proteins even after hypoxia / reoxygenation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE AND DESIGN : The purpose of the present study was to evaluate the effect of urethane , pentobarbital sodium and ketamine xylazine anesthesia upon constitutive and inducible cyclooxygenase ( COX 1 ; COX 2 ) and nitric oxide synthase ( eNOS ; iNOS ) mRNA levels in the lung . ^^^ MATERIAL : Sprague Dawley rat lungs RESULTS : Urethane significantly decreased COX 1 and COX 2 mRNA levels to 30 % of control values . ^^^ Pentobarbital sodium and ketamine had no effect on the mRNA levels for COX 1 and COX 2 the lung . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To measure COX 2 activity , cells were transiently pre treated with aspirin to irreversibly inhibit constitutive COX 1 , treated with lipopolysaccharide ( LPS ) to induce COX 2 and then stimulated with AA . ^^^ RESULTS : Eicosanoid production in resting monocytes was predominantly COX 1 derived since it was not inhibited by NS 398 and also , COX 2 was not detectable . ^^^ Using the mean of the results for PGE 2 and TXB 2 inhibition , the COX 1 / COX 2 ratios of the IC 50 values for aspirin and NS 398 are < 0 . 1 and > 130 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The anti inflammatory and renal effects of conventional NSAIDs are mediated by the non selective inhibition of two cyclo oxygenases , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the rate limiting enzyme in PG biosynthesis , exists in two isoforms , COX 1 and COX 2 . ^^^ Here we describe for the first time the heightened expression of COX 2 and PPARdelta , but not COX 1 , in uterine endometrial adenocarcinoma . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX is expressed in two isoforms , constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We used quantitative Northern analysis to assay the transcript levels of three mitochondrially encoded components of the cytochrome c oxidase complex ( cox 1 , cox 2 , and cox 3 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 sparing and COX 2 inhibitory drugs : the renal and hepatic safety and tolerability profiles of celecoxib . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The identification of an inducible isoform , COX 2 , besides the constitutive one , COX 1 , suggested that the latter was dedicated to cytoprotection , whereas the former was responsible for inflammation and neoplasia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Most nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit both cyclooxygenase 1 ( COX 1 ) , whose inhibition is associated with gastrointestinal ulceration , and COX 2 , whose inhibition is associated with therapeutic benefits . ^^^ Although agents that do not produce COX 1 activity may have fewer adverse effects , targeted disruption of the COX 2 allele in mice has resulted in severe renal problems , suggesting that COX 2 inhibition may also produce adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pulse chase analysis of mitochondrial translation revealed decreased rates of translation of COX 1 , COX 2 , and COX 3 mRNAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As did the membrane bound PGE ( 2 ) synthase , the perinuclear enzymes thromboxane synthase and PGI ( 2 ) synthase generated their respective products via COX 2 in preference to COX 1 in both the induced immediate and interleukin 1 induced delayed responses . ^^^ Hematopoietic PGD ( 2 ) synthase preferentially used COX 1 and COX 2 in the induced immediate and interleukin 1 induced delayed PGD ( 2 ) biosynthetic responses , respectively . ^^^ This enzyme underwent stimulus dependent translocation from the cytosol to perinuclear compartments , where COX 1 or COX 2 exists . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The results show that liver regeneration is markedly impaired when both COX 1 and COX 2 are inhibited by indocin or by a combination of the COX 1 selective antagonist , SC 560 , and the COX 2 selective antagonist , SC 236 . ^^^ Inhibition of COX 2 alone partially inhibits regeneration whereas inhibition of COX 1 alone tends to delay regeneration . ^^^ These data indicate that prostaglandin signaling is required during liver regeneration , that COX 2 plays a particularly important role but COX 1 is also involved , and implicate the activation of CREB rather than STAT 3 as the mediator of prostaglandin signaling during liver regeneration . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Based on RT PCR and Northern blot analysis , growth zone chondrocytes expressed mRNAs for both Cox 1 and Cox 2 and neither Cox was modulated by 1alpha , 25 ( OH ) ( 2 ) D ( 3 ) . ^^^ To examine the role of Cox , the cultures were also treated with resveratrol ( a specific inhibitor of Cox 1 ) , NS 398 ( a specific inhibitor of Cox 2 ) , or indomethacin ( a general Cox inhibitor ) . ^^^ The results showed that Cox 1 inhibition reduced the 1alpha , 25 ( OH ) ( 2 ) D ( 3 ) dependent effects on proliferation , differentiation , and matrix production , whereas inhibition of Cox 2 only had an effect on proliferation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we investigated a role of COX isoforms ( COX 1 and COX 2 ) in kainic acid induced neuronal death in cultured murine cortical or hippocampal neurons . ^^^ In conclusion , we suggest that the release of PGE ( 2 ) induced by kainic acid occurred through COX 1 activity rather than COX 2 in cortical neurons . ^^^ The inhibition of PGE ( 2 ) release by COX 1 inhibitors prevented kainic acid induced cortical neuronal death , while in the hippocampal neurons , COX 2 inhibitors prevented kainic acid induced PGE ( 2 ) release and hippocampal neuronal death . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Platycodin D showed no direct effect on COX 1 and COX 2 activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The new compounds were evaluated both in vitro ( COX 1 and COX 2 inhibition in human whole blood ) and in vivo ( carrageenan induced paw edema and air pouch model ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Much has been written about NSAIDs and COX , since the discovery of COX 1 and COX 2 isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since NSAIDs are known to inhibit cyclooxygenases ( COX 1 , COX 2 ) , the basic mechanism of their antitumor effects is conceivably the altered metabolism of arachidonic acid and , subsequently , prostaglandins ( PGs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The key enzymes of prostaglandin synthesis , cyclooxygenase 1 ( Cox 1 ) and 2 ( Cox 2 ) , were present in all unaltered and preneoplastic cells and tended to decrease in the later stages of hepatocarcinogenesis . ^^^ Cox 1 and Cox 2 were present in all cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 was detected as the major isoform by immunoblot analysis in extracts from aortas of normal and 8 week cholesterol fed animals with COX 2 being induced in atherosclerotic plaques from cholesterol fed animals . ^^^ Furthermore , COX 2 expression is induced in atherosclerotic plaques and may play a role in altering localized synthesis of prostanoids in these lesions but does not appear to significantly impact the arachidonic acid dependent prostacylin production of aortic tissues , which is largely mediated by COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE ( 2 ) production by C3L5 cells was primarily owing to COX 2 , since this was blocked similarly with non selective COX inhibitor indomethacin and selective COX 2 inhibitor NS 398 , but unaffected with the selective COX 1 inhibitor valeryl salicylate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All tumor cell lines examined , regardless of phenotype , express both cox 1 and cox 2 proteins in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two cyclooxygenase isozymes , constitutive COX 1 and inducible COX 2 , has resulted in the rapid development of selective inhibitors of COX 2 , such as celecoxib and rofecoxib . ^^^ Compared with traditional non steroidal anti inflammatory drug agents , use of COX 2 selective inhibitors is associated with decreased incidence of adverse gastric events as a result of minimal inhibition of gastroprotective COX 1 , but with equivalent anti inflammatory benefit through inhibition of COX 2 . ^^^ However , there is evidence to suggest that the ' COX 1 = constitutive , COX 2 = inflammatory ' paradigm is less distinct than originally proposed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The other conspicuous features of this molecule are : a large ( 3018 nucleotides ) in frame insertion of unknown function in the cox 2 gene ; the presence of two different lineages of group 2 introns , including complete reverse transcriptase like genes , one in the cox 1 and the other in the rnl gene ; the concomitant occurrence of a T 7 like RNA polymerase and of several well conserved alpha proteobacterial type promoters ; and a small nad 11 gene , coding for the first domain only of this NADH dehydrogenase subunit . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The selective cyclooxygenase 2 ( COX ) inhibitor , celecoxib , and the non selective COX 1 and COX 2 inhibitor , indomethacin , at microM concentrations , stimulate the release of arachidonic acid from rat liver cells ( the C 9 cell line ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been identified : a constitutive COX 1 and an inducible COX 2 , which is activated in response to various stimuli . ^^^ We investigated the changes of COX 1 and COX 2 in rat heart during aging . ^^^ COX 2 mRNA and protein levels increased with age , whereas those of COX 1 showed no change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The acute antihyperalgesic action of nonsteroidal , anti inflammatory drugs and release of spinal prostaglandin E 2 is mediated by the inhibition of constitutive spinal cyclooxygenase 2 ( COX 2 ) but not COX 1 . ^^^ Western blots show the constitutive expression of COX 1 and COX 2 in the rat spinal dorsal and ventral horns and in the dorsal root ganglia . ^^^ This intrathecally evoked release of spinal PGE ( 2 ) was diminished by systemic delivery of nonspecific COX and COX 2 selective inhibitors , but not a COX 1 selective inhibitor . ^^^ Given at systemic doses that block SP and carrageenan evoked hyperalgesia , COX 2 , but not COX 1 , inhibitors reduced spinal SP evoked PGE ( 2 ) release . ^^^ Thus , constitutive spinal COX 2 , but not COX 1 , is an important contributor to the acute antihyperalgesic effects of spinal as well as systemic COX 2 inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSION : After unilateral chest trauma , Mphi COX 1 , not COX 2 , is induced bilaterally and before fluid resuscitation ; CYC prevented PMN infiltration and attenuated structural and functional changes after resuscitation , which suggests that PMNs have a role in the pathogenic mechanism of secondary lung injury ; Mphi COX expression and other injury markers were not altered by CYC ; and since Mphis continued to express proinflammatory COX protein even after pretreatment with a powerful nonspecific immunosuppressant , and since there is residual alveolar capillary damage even in the absence of PMNs , it is logical to conclude that no single cell type or mediator is a practical therapeutic target and that novel resuscitation strategies must address multiple elements in the inflammatory cascade . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : The cyclooxygenase ( COX ) enzymes exist in two related but unique isoforms ( COX 1 and COX 2 ) and catalyze the formation of prostaglandins ( PGs ) . ^^^ METHODS : In this study , we evaluated COX 1 and COX 2 expression in 30 polyps collected from 10 patients with familial adenomatous polyposis ( FAP ) and in 18 polyps collected from 18 patients with sporadic adenomatous polyposis ( SAP ) using COX 1 or COX 2 isoform specific antibodies . ^^^ CONCLUSIONS : COX 2 expression is upregulated in the adenomatous epithelium of SAP and FAP , while the COX 1 isoform appears to be constitutively expressed at low levels in both neoplastic and non neoplastic regions . ^^^ The differential expression of COX 1 and COX 2 in these neoplasms suggests that COX 2 rather than COX 1 may play a role in adenoma formation and / or growth in cases of SAP and FAP in humans . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , COX 2 gene ablated mice are unable to develop a febrile response to intraperitoneal ( i . p . ) LPS , whereas their COX 1 deficient counterparts produce fevers not different from their wild type ( WT ) controls . ^^^ To extend the apparently critical role of COX 2 for LPS induced fevers to fevers produced by endogenous pyrogens , we studied the thermal responses of COX 1 and COX 2 congenitally deficient mice to i . p . and intracerebroventricular ( i . c . v . ) injections of recombinant murine ( rm ) interleukin ( IL ) 1beta . ^^^ We also assessed the effects of one selective COX 1 inhibitor , SC 560 , and two selective COX 2 inhibitors , nimesulide ( NIM ) and dimethylfuranone ( DFU ) , on the febrile responses of WT and COX 1 ( / ) mice to LPS and rmIL 1beta , i . p . ^^^ I . p . and i . c . v . rmIL 1beta induced similar fevers in WT and COX 1 knockout mice , but provoked no rise in the T ( c ) s of COX 2 null mutants . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we evaluated the levels of nitric oxide synthase , both neuronal and induced ( nNOS and iNOS , respectively ) , cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) and protein kinase C gamma ( PKCgamma ) and correlated these with algogenic behavior following spinal kainic acid ( KA ) receptor activation in rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 immunostaining was similar to that of COX 2 in the lungs of urethane injected mice treated with or without indomethacin . ^^^ By RT PCR , COX 1 and COX 2 PCR products were present in mouse lung adenomas , alveoli and bronchioli . ^^^ These results suggest that indomethacin may inhibit COX 1 and COX 2 in the A / J mouse lung resulting in reduced adenoma formation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Orally administered celecoxib ( COX 2 inhibition ) or high dose aspirin ( HDA ) ( COX 1 and COX 2 inhibition ) did not alter time to occlusive thrombus formation compared with controls ( celecoxib 77 . 7+ / 7 . 2 minutes , HDA 72 . 0+ / 18 . 5 minutes , control 93 . 0+ / 21 . 8 minutes ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of the enzyme cyclooxygenase have been identified : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two COX isoenzymes , namely the constitutively expressed COX 1 and the inducible COX 2 . ^^^ COX 2 is overexpressed in adenomas and colorectal cancers , and COX 2 specific inhibitors have been shown to inhibit intestinal polyps in Apc ( Delta 716 ) mice more effectively than dual COX 1 / COX 2 inhibitors such as sulindac . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , neither the location of the COX involved nor the specific isoform , COX 1 or COX 2 , is known . ^^^ A previous study using selective COX 1 and COX 2 inhibitors did not provide an unequivocal answer . ^^^ Therefore , we tested the response of sweetened milk ingestion to IL 1 and LPS in mice in which the COX 1 or the COX 2 gene was deleted ( COX1ko and COX2ko ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of PGHS exist , PGHS 1 ( COX 1 ) and PGHS 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , both metabolize arachidonic acid to PGH ( 2 ) , the common substrate for thromboxane A ( 2 ) ( TXA ( 2 ) ) , prostacyclin ( PGI ( 2 ) ) , and PGE ( 2 ) synthesis . ^^^ We characterized the synthesis of these prostanoids in HUVECs in relation to COX 1 and COX 2 activity . ^^^ Untreated HUVEC expressed only COX 1 , whereas addition of IL 1beta caused induction of COX 2 . ^^^ TXA ( 2 ) was the predominant COX 1 derived product , and TXA ( 2 ) synthesis changed little with up regulation of COX 2 by IL 1beta ( 2 fold increase ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
With the same treatment schedule , however , rutaecarpine failed to alter the activities of cellular COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX has recently been shown to have at least two isoforms , termed COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the key enzyme for synthesis of prostaglandins , exists in two isoforms ( COX 1 and COX 2 ) . ^^^ On this premise selective COX 2 inhibitors not affecting COX 1 in the gastrointestinal tract mucosa have been developed as gastrointestinal sparing anti inflammatory drugs . ^^^ Thus gastric and intestinal lesions do not develop when COX 1 is inhibited but only when the activity of both COX 1 and COX 2 is suppressed . ^^^ These observations support the concept that COX 2 represents ( in addition to COX 1 ) a further line of defence for the gastrointestinal mucosa necessary for maintenance of mucosal integrity and ulcer healing . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study examined ( a ) the seroprevalence of HP , its cytotoxic protein , CagA , and cytokines ( tumor necrosis factor alpha , interleukins 1beta and 8 ) in 80 patients with colorectal cancers , before and after the removal of tumor , compared with 160 age and gender matched controls ; ( b ) the gene expression of gastrin and its receptors ( CCKB R ) in the cancer tissue , ( c ) the plasma levels and tumor tissue contents of gastrin , and ( d ) the mRNA expression of COX 1 , COX 2 , and apoptotic proteins ( Bax and Bcl 2 ) in cancer tissue and intact colonic mucosa . ^^^ Anti HP IgG , anti CagA IgG seroprevalence , and cytokine levels were analyzed by enzyme linked immunosorbent assay tests ; gene expressions of gastrin , CCKB R , COX 1 , COX 2 , Bax , and Bcl 2 by reverse transcriptase polymerase chain reaction ; and gastrin by radioimmunoassay . ^^^ Both gastrin and CCKB R mRNA were detected in the cancer tissue and the resection margin ; similarly , COX 2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa , where only COX 1 was detected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gene expressions of gastrin , CCK ( B ) R , COX 1 and COX 2 were examined using RT PCR with beta actin as a reference and employing Western blotting for COX 2 expression , while gastrin and PGE 2 were measured by RIA . ^^^ Similarly , COX 2 mRNA and protein were found in margin of gastric ulcer and in the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated patients in whom ulcers completely healed and gastrin was expressed only in antrum , CCK ( B ) R only in corpus , while COX 1 was detected both in antrum and corpus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , 2 , 3 dimethyl 5 ( 4 methylsulfonylphenyl ) 4 phenyl 4 isoxazoline ( 13j ) exhibited excellent analgesic and AI activities , and it was a potent and selective COX 2 inhibitor ( COX 1 , IC ( 50 ) = 258 microM ; COX 2 , IC ( 50 ) = 0 . 004 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The azido analogue of rofecoxib ( 17 ) , the most potent and selective inhibitor of COX 2 ( COX 1 IC ( 50 ) = 159 . 7 microM ; COX 2 IC ( 50 ) = 0 . 196 microM ; COX 2 selectivity index = 812 ) , exhibited good oral antiinflammatory and analgesic activities . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we have synthesised a series of novel substituted benzamides , related to Parsalmide , and have evaluated their activity in vitro on COX 1 and COX 2 as well as in vivo in the carrageenin induced rat paw edema , a classical in vivo anti inflammatory assay . ^^^ Results obtained showed that Parsalmide and compound 11b inhibited both COX 1 and COX 2 in vitro as well as they were active in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The conditions under which COX 1 and COX 2 are expressed and upregulated in human RPE ( HRPE ) cells were determined . ^^^ RESULTS : Examination of untreated RPE cells revealed the presence of COX 2 mRNA and the absence of COX 1 mRNA . ^^^ Moreover , cytokine stimulation more readily enhanced COX 2 gene expression than COX 1 gene expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although there was an accompanying elevation of COX 1 and COX 2 mRNA , Stx 1 decreased and LPS did not change COX 1 and COX 2 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis shows that COX 1 and COX 2 isoenzymes are present before and after 5 h in vitro incubation and apparently COX 2 does not suffer additional induction . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , gene expression of cyclooxygenase 1 ( COX 1 ) and COX 2 and apoptosis related proteins such as Bax and Bcl 2 are discussed . ^^^ COX 1 was similarly expressed in GC and MALT as in intact mucosa , while COX 2 mRNA was detected only in tumor tissue , being attenuated by H . pylori eradication in GC and abolished by this therapy in MALT lymphoma . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND / AIMS : Ulcer healing involves expression of various growth factors such as epidermal growth factor ( EGF ) , hepatocyte growth factor ( HGF ) and basic fibroblast growth factor ( bFGF ) at the ulcer margin , but the influence of EGF , HGF and bFGF applied locally with or without neutralizing anti EGF , HGF and bFGF antibodies or cyclooxygenase ( COX ) 1 and COX 2 inhibitors on ulcer healing and the expression of COX 1 and COX 2 during ulcer healing have only been studied a little . ^^^ On days 13 and 21 , the ulcer area was determined by planimetry , gastric blood flow ( GBF ) at the ulcer margin was examined by the H 2 gas clearance technique , and mucosal generation of PGE 2 and the gene expression of COX 1 and COX 2 in the non ulcerated and ulcerated gastric mucosa were assessed . ^^^ Local treatment with EGF , HGF and bFGF produced a significant decrease in gastric acid secretion and significantly accelerated the rate of ulcer healing and raised GBF at the ulcer margin causing further significant upregulation of COX 2 but not COX 1 expression in the ulcerated mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : We evaluated the dual acting antiinflammatory drug ML 3000 ( 2 , 2 dimethyl 6 ( 4 chlorophenyl ) 7 phenyl 2 , 3 dihydro H pyrrolizine 5 yl ) acetic acid , a dual inhibitor of 5 lipoxygenase ( 5 LOX ) as well as both cyclooxygenases ( COX 1 and COX 2 ) in the rat model of adjuvant arthritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Different levels of COX 1 and COX 2 enzymes in synoviocytes and chondrocytes during joint contracture formation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The protein encoding genes are similar in size , composition and codon usage in all species except for cox 1 in S . mansoni ( 609 aa ) and cox 2 in S . mekongi ( 219 aa ) , both of which are longer than homologues in other species . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These enzymes ( Cox 1 and Cox 2 ) catalyze the synthesis of eicosanoids , which play an important part in platelet vessel wall interactions . ^^^ Aspirin is a more potent inhibitor of Cox 1 than of Cox 2 , unlike other non steroidal anti inflammatory drugs ( NSAIDs ) , which have limited selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of the two COX isoforms , namely COX 1 ( constitutive ) and COX 2 ( inducible ) led to the search for specific COX 2 inhibitors with better gastrointestinal safety . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Finally , cyclooxygenase inhibitory potency of the drugs was also tested in both a cell free system using purified ovine cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) and at a cellular level using human whole blood assay . ^^^ In the whole blood test , aceclofenac and 4 ' hydroxyaceclofenac weakly inhibited COX 1 with IC 50 values superior to 100 microM , but decreased by 50 % COX 2 activity at the concentration of 0 . 77 and 36 microM , respectively . ^^^ Diclofenac strongly inhibited both COX 1 and COX 2 with IC 50 values of 0 . 6 and 0 . 04 microM , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis showed a reduced concentration of both COX 2 and COX 1 polypeptides , suggesting impaired assembly of COX holoenzyme . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The energetics and models of COX 2 complexed with nonsteroidal anti inflammatory drugs ( NSAIDs ) having different degrees of selectivity for two isoforms of COX ( COX 2 and COX 1 ) have been studied using computer modelling approach . ^^^ In case of NS a larger difference in the binding energies between COX 2 and COX 1 was noticed as compared to that of Ind . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our results suggest that in a model of systemic inflammation characterized by the absence of COX 2 protein expression , NOS 2 derived NO activates COX 1 pathway , and inhibitors of COX isoforms have no effect on NOS 2 or NOS 3 ( endothelial NOS ) pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our results suggest that therapeutic approaches based on long term blocking including COX 1 , might be superior to selective COX 2 blocking to suppress the local synthesis of prostanoids . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme have been identified which are referred to as COX 1 and COX 2 . ^^^ Under most circumstances , COX 1 is produced constitutively , whereas COX 2 can be induced by several physiological stimuli and is expressed at sites of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibitors . ^^^ The recognition that there are two cyclo oxygenase enzymes , one predominating at sites of inflammation ( COX 2 ) and one constitutively expressed in the gastrointestinal tract ( COX 1 ) , has led to the important therapeutic development of COX 2 inhibitors . ^^^ COX 2 is phylogenetically more primitive that COX 1 and , while very similar , has critical differences , particularly the existence of a small pocket half way down the active enzyme site . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The advent of specific COX 2 inhibitors , which do not interfere with the cytoprotective constitutive COX 1 enzyme , and the demonstration of increased COX 2 expression in many common malignancies beside colorectal cancer , has opened up new therapeutic possibilities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Curcumin markedly inhibited the mRNA and protein expression of COX 2 , but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Stomach , small bowel , and large bowel COX 1 and COX 2 mRNA levels ( reverse transcription polymerase chain reaction technique ) and protein content ( Western blot ) were obtained from neonates ( younger than 3 days old ) and adult rats 18 hours after exposure to E . coli O 111 : B 4 lipopolysaccharide toxin . ^^^ After lipopolysaccharide exposure , no significant changes in COX 1 levels were seen at either age , whereas COX 2 mRNA levels were increased only in the stomach for both ages . ^^^ Western blot analysis of small bowel tissue for COX 1 and COX 2 showed no lipopolysaccharide induced changes in protein content , but the COX 1 content was significantly lower in the newborn ( P < 0 . 01 ) . ^^^ Lower COX 1 expression and a lack of observable increase in COX 2 mRNA levels in the newborn small bowel after endotoxemia may render the bowel more susceptible to bowel injury early in life . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , the tolerance profile varies with the drug , which might be related to a differential selectivity of the drug for COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Total RNA was extracted and reverse transcriptase PCR analysis performed for the mRNA of COX 2 , COX 1 , the microglial marker CD11b , and the housekeeping gene cyclophilin . ^^^ RESULTS : In ALS compared with non ALS spinal cord , COX 2 mRNA was upregulated 7 . 09 fold ( p < 0 . 0001 ) , COX 1 1 . 14 fold ( p = 0 . 05 ) , and CD11b 1 . 85 fold ( p = 0 . 0012 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Conventional non steroidal antiinflammatory drugs ( NSAIDs ) inhibit both COX 1 and COX 2 . ^^^ The analgesic , antipyretic and antiinflammatory effects of these agents are accounted for by COX 2 inhibition , whereas the toxic effects on the stomach as well as the inhibition of platelet aggregation are attributed to COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of cyclooxygenase 2 ( cox 2 ) is considered to be anti inflammatory , whereas inhibition of the constitutive isozyme cox 1 causes renal and gastrointestinal toxicity . ^^^ Therefore , to achieve an optimal anti inflammatory effect , an inhibitor should be cox 2 selective without inhibiting cox 1 . ^^^ The colonic levels of cox 2 protein , mRNA , myeloperoxidase ( MPO ) , and prostaglandin E 2 ( PGE 2 ) were increased significantly on day 1 and remained significantly elevated until day 7 post TNBS administration , whereas cox 1 remained unaltered . ^^^ Two S oligos were found to be effective in reducing the level of cox 2 protein selectively without any effect on the cox 1 . ^^^ The effective S oligo reduced the level of cox 2 but not the cox 1 mRNA significantly , whereas a mismatched or a sense control oligo did not affect the levels of these isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 selective inhibitors : aspirin , a dual COX 1 / COX 2 inhibitor , to COX 2 selective inhibitors ] . ^^^ During the century after that , aspirin has been found to show its anti inflammatory , analgesic and anti pyretic activities by reducing prostaglandins biosynthesis through inhibition of cyclooxygenase ( COX ) ; and then COX was found to be constituted of two isoforms , constitutive COX 1 and inducible COX 2 . ^^^ Physiological and pathophysiological roles of COX 1 and COX 2 have been explained from studies in experimental animals , but there are many differences in species and diseases between animals and humans . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By immunohistochemistry and real time RT PCR , COX 2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end stage POAG , whereas COX 1 expression was unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RA acted synergistically with LPS to increase plasma ( 400 fold ) and liver ( 15 fold ) concentrations of prostaglandin E ( 2 ) ( PGE ( 2 ) ) and significantly , but to a lesser extent , other PG compared with RA rats , in the absence of major differences in PLA ( 2 ) expression or activity or COX 1 and COX 2 mRNA or protein expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in a wide range of tissues , whereas COX 2 is cytokine inducible . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 2 ( COX 2 ) is an inducible enzyme homologous to COX 1 that is responsible for production of prostaglandins at sites of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists in 2 isoforms , COX 1 and COX 2 . ^^^ To better understand the roles of these genes in head and neck squamous cell carcinoma ( HNSCCA ) , we examined the differential expression of the COX 1 , COX 2 , VEGF , and PPARdelta genes in these tumors . ^^^ Tissue samples from patients with HNSCCA were analyzed for COX 1 , COX 2 , VEGF , and PPARdelta messenger RNAs ( mRNAs ) by in situ hybridization . ^^^ COX 1 and COX 2 mRNAs were also evaluated with Northern blot hybridization . ^^^ Results showed focal areas of accumulation for COX 2 , VEGF , and PPARdelta but not COX 1 in human HNSCCA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The production of proMMPs 1 and 3 , TIMPs 1 and 2 , cyclooxygenase 1 ( COX 1 ) and COX 2 , prostaglandin E 2 ( PGE 2 ) , IL 1beta , and IL 6 was assayed by Western blot analysis and enzyme linked immunosorbent assay . ^^^ Gene expression of proMMPs 1 and 3 , TIMPs 1 and 2 , COX 1 and COX 2 , IL 1alpha , IL 1beta , tumor necrosis factor alpha ( TNFalpha ) , and IL 6 was also monitored by Northern blot analysis and reverse transcriptase polymerase chain reaction . ^^^ Triptolide also inhibited the IL 1alpha induced production of PGE 2 by selectively suppressing the gene expression and production of COX 2 , but not those of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin biosynthesis is catalysed by the enzyme cyclooxygenase ( COX ) , which exists in two isoforms , COX 1 and COX 2 . ^^^ Initially the concept was developed that COX 1 functions as housekeeping enzyme , whereas COX 2 yields prostaglandins involved in pathophysiological reactions such as inflammation . ^^^ In the gastrointestinal tract , the maintenance of mucosal integrity was attributed exclusively to COX 1 without a contribution of COX 2 and ulcerogenic effects of non steroidal anti inflammatory drugs ( NSAIDs ) were believed to be the consequence of inhibition of COX 1 . ^^^ Recent findings , however , indicate that both COX 1 and COX 2 either alone or in concert contribute to gastric mucosal defence . ^^^ When a selective COX 2 inhibitor which is not ulcerogenic when given alone is added to the COX 1 inhibitor , severe gastric damage develops . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The recent much heralded development of COX 2 selective drugs ( celecoxib , rofecoxib ) , the objective of which has been to spare inhibition of the production of COX 1 derived mucosal protective prostaglandins , may have represented an advance in reducing the risk of serious ADRs ulcers and bleeding but does not appear to have reduced the incidence of symptomatic side effects ( nausea , vomiting , epigastric pain / heartburn , abdominal discomfort ) which are a major reason for withdrawal from NSAID therapy , especially in the long term . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of both COX 1 and COX 2 is required for development of gastric damage in response to nonsteroidal antiinflammatory drugs . ^^^ We examined the gastric ulcerogenic property of selective COX 1 and / or COX 2 inhibitors in rats , and investigated whether COX 1 inhibition is by itself sufficient for induction of gastric damage . ^^^ On the other hand , the COX 2 mRNA was expressed in the stomach after administration of SC 560 , while the normal gastric mucosa expressed only COX 1 mRNA but not COX 2 mRNA . ^^^ These results suggest that the gastric ulcerogenic property of conventional NSAIDs is not accounted for solely by COX 1 inhibition and requires the inhibition of both COX 1 and COX 2 . ^^^ The inhibition of COX 1 up regulates the COX 2 expression , and this may counteract the deleterious influences , such as gastric hypermotility and the subsequent events , due to a PG deficiency caused by COX 1 inhibition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 inhibitors ( coxibs ) rofecoxib and celecoxib are highly selective inhibitors of COX 2 , differentiating them from nonselective NSAIDs , which substantially inhibit both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two distinct COXs have been identified : COX 1 which is constitutively expressed and COX 2 which is induced by different products such as tumor promoters or growth factors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To evaluate the involvement of COX dependent and COX independent mechanisms further , we assessed the effects of celecoxib ( selective COX 2 inhibitor ) and SC 560 ( selective COX 1 inhibitor ) on cell survival , cell cycle distribution , and apoptosis in three colon cancer cell lines , which differ in their expression of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Also , we investigated the role of PGE ( 2 ) in sepsis related changes in T cell [ Ca ( 2+ ) ] ( 1 ) in animals pretreated with cyclooxygenase 1 ( COX 1 ) inhibitor ( resveratrol ) and cyclooxygenase 2 ( COX 2 ) inhibitor ( NS 398 ) . ^^^ Pretreatment of pups with COX 2 , but not COX 1 inhibitor , prevented the decrease in the [ Ca ( 2+ ) ] ( 1 ) response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All the compounds were shown to be docked at the site where intact flurbiprofen was embedded for COX 1 and s 58 ( 1 phenylsulphonamide 3 trifluoromethyl 5 para bromophenylpyrazole ) for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Partial suppression of serum thromboxane B ( 2 ) synthesis resulting from platelet COX 1 activity and complete inhibition of urinary 6 keto prostaglandin F ( 1alpha ) , reflecting endothelial COX 2 activity , indicate preferential inhibition of COX 2 by nimesulide . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : Cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) enzymes catalyze the initial step in the formation of prostaglandins , which have a role in the regulation of circulation and in inflammatory reactions . ^^^ As hypoxia is reported to stimulate the expression of COX 2 , we have investigated the effects of bypass circulation and cardioplegic arrest on the expression COX 1 and COX 2 in the myocardium of porcine hearts . ^^^ Then the mRNA and protein levels of COX 1 and COX 2 were measured from the transmural specimens of the left ventricular myocardium by Northern and Western blot analyses . ^^^ RESULTS : COX 1 mRNA was expressed in unoperated control porcine hearts , whereas the expression of COX 2 mRNA was weak in control hearts . ^^^ The expression of COX 2 mRNA increased to 170 % of the control level in the hearts of sham operated pigs and to 180 % in arrested hearts , while the level of COX 1 mRNA was not changed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin synthesis by cyclooxygenases 1 and 2 ( COX 1 and COX 2 ) involves an initial oxygenation of arachidonic acid at C 11 , followed by endoperoxide and cyclopentane ring formation , and then a second reaction with molecular oxygen in the S configuration at C 15 . ^^^ Using human COX 1 and human and murine COX 2 , we have identified two amino acids located in the oxygenase active site that control the stereochemistry at C 15 . ^^^ When Val 349 was replaced by isoleucine , the mutant COX 1 and COX 2 enzymes formed 41 and 65 % 15R prostaglandins , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of cyclooxygenase , Cox 1 constitutive and Cox 2 inducible , has prompted the development of new molecules with high Cox 2 selectivity . ^^^ The selective inhibition of Cox 2 with no effect on Cox 1 favors cardiovascular events in patients at risk . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
None of these manoeuvres changed medullary COX 2 expression or cortical or medullary COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
On the other hand , while COX 1 expression in mononuclear cells was prominent in normal and FAP mucosa , densitometric analysis showed immunoreactive prostaglandin endoperoxide synthase levels were further increased in FAP , due to a greater than fourfold elevation of COX 2 expression among mononuclear cells and epithelia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gene expressions of gastrin , CCK ( B ) R , COX 1 , COX 2 and Bax and Bcl 2 was examined using RT PCR , while gastrin was measured by RIA . ^^^ Gastrin and CCK ( B ) R mRNA were detected in the cancer tissue and the resection margin and similarly COX 2 mRNA was expressed in most of cancers and their resection margin but not in intact colonic mucosa where only COX 1 was detected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The isozymes cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) catalyze the conversion of arachidonic acid to eicosanoids that play an important role in the maintenance of cardiovascular hemostasis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BAL macrophage and lymphocyte numbers increased in BALB mice ( P < 0 . 0007 and 0 . 02 , respectively ) , as did BAL protein content ( P < 0 . 05 ) , COX 1 and COX 2 expression ( P < 0 . 05 for each ) , and PGI ( 2 ) production ( P < 0 . 05 ) ; conversely , these indices were not perturbed by BHT in CXB 4 mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , the inhibition of COX 1 results in defective induction of the COX 2 gene , which behaves as an early TCR responsive gene . ^^^ The data identify COX 1 and COX 2 as integral and sequential components of TCR signaling to p 38 and contribute to elucidate the molecular basis of immunosuppression by NSAID . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( Cox ) is the key enzyme in conversion of arachidonic acid to PGs , and two isoforms , Cox 1 and Cox 2 , have been identified . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Treatment with highly selective cyclooxygenase 2 inhibitors is associated with significantly fewer serious adverse gastrointestinal events than is treatment with non selective NSAIDs , provided that the drug employed inhibits COX 2 but not COX 1 at therapeutic plasma levels . ^^^ The wider the separation between the COX 2 and COX 1 dose response curves of the inhibitor ( an index of biochemical selectivity ) , the lower the probability of experiencing a clinically relevant inhibition of platelet COX 1 due to an unusually high drug level or intense pharmacodynamic response to a normal drug level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Such agents should be devoid of COX 1 related side effects in , for example , the inhibition of blood coagulation and should only weakly affect COX 2 related functions of the central nervous system , due to slow blood brain barrier penetration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia , and the in vivo selectivity of a selective cyclooxygenase ( COX ) 2 inhibitor ( celecoxib ) in comparison to a dual COX 1 / COX 2 inhibitor ( ketorolac ) . ^^^ Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E 2 ( PGE 2 ; a product of both COX 1 and COX 2 ) and thromboxane B 2 ( as a biomarker for COX 1 activity ) with parallel assessments of pain . ^^^ The time course of PGE 2 production was consistent with early release due to COX 1 activity followed by increased production 2 3 hours after surgery , consistent with COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROCEDURE : Activities of COX 1 and COX 2 were determined by measuring coagulation induced thromboxane and lipopolysaccharide induced prostaglandin E 2 concentrations , respectively , in whole blood with and without the addition of various concentrations of phenylbutazone , flunixin meglumine , ketoprofen , diclofenac , indomethacin , meloxicam , carprofen , 5 bromo 2 [ 4 fluorophenyl ] 3 14 methylsulfonylphenyl ] thiophene ( DuP 697 ) , 5 , 5 dimethyl 3 ( 3 fluorophenyl ) 4 ( 4 methylsulphonyl ) phenyl 2 ( 5H ) furan one ( DFU ) , 3 ( 3 , 4 difluorophenyl ) 4 ( 4 ( methylsulfonyl ) phenyl ) 2 ( 5H ) furanone ( MF tricyclic ) , and celecoxib . ^^^ Selectivity was determined by calculating the ratio of IC 50 for COX 1 to IC 50 for COX 2 ( COX 1 / COX 2 ratio ) . ^^^ RESULTS : The novel compound DFU was the most selective COX 2 inhibitor in equine , canine , and feline blood ; COX 1 / COX 2 ratios were 775 , 74 , and 69 , respectively . ^^^ In contrast , NSAID such as phenylbutazone and flunixin meglumine were more potent inhibitors of COX 1 than COX 2 in canine and equine blood . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostanoid synthesis is regulated by the enzyme cyclo oxygenase ( COX ) , which is present in at least two isoforms , COX 1 ( the constitutive form ) and COX 2 ( the inducible form ) . 3 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since it is yet unclear which of the isoforms of cyclooxygenases , COX 1 and COX 2 , is relevant in this context , our study aimed to determine the effects of selective COX 2 inhibition on the renal effects of the loop diuretic furosemide , as well as the diuretic hydrochlorothiazide , which acts on the distal tubule . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The homogenates of bovine platelets and polymorphonuclear leukocytes were used as COX 1 , 12 LOX , and 5 LOX enzyme sources ; the homogenate of aspirin pretreated lipopolysaccharide induced RAW 264 . 7 cells was used for the COX 2 enzyme source . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We analyzed liver histopathology , lipid peroxidation , cytochrome P 450 ( CYP ) 2E1 activity , nonheme iron , endotoxin , nuclear factor kappa B ( NF kappa B ) activation , and mRNA levels of cyclooxygenase 1 ( COX 1 ) and COX 2 , tumor necrosis factor alpha ( TNF alpha ) , monocyte chemotactic protein 1 ( MCP 1 ) , and macrophage inflammatory protein 2 ( MIP 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS AND RESULTS : Compared with hearts from wild type ( WT ) and COX 2 ( / ) mice , baseline cardiac prostaglandin ( PG ) E ( 2 ) and 6 keto PGF ( 1alpha ) levels were significantly decreased in hearts from COX 1 ( / ) mice . ^^^ After ischemia , cardiac PGE ( 2 ) levels increased in WT , COX 1 ( / ) , and COX 2 ( / ) mice ( P < 0 . 05 ) . ^^^ Recovery of function ( LVDP ) after global ischemia in hearts from COX 1 ( / ) and COX 2 ( / ) mice was significantly less than in WT hearts . ^^^ Postischemic recovery of LVDP in COX 1 ( / ) and COX 2 ( / ) was unchanged by perfusion with 5 micromol / L PGE ( 2 ) , PGD ( 2 ) , PGF ( 2alpha ) , or carboprostacyclin . ^^^ Hearts from COX 2 ( / ) mice showed an increase in ischemic contracture compared with hearts from WT and COX 1 ( / ) mice ; however , hearts did not differ in intracellular pH , ATP , or inorganic phosphate during ischemia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Transcripts for COX 1 , COX 2 , TX synthase ( TXS ) , and PGE 2 synthase ( PGES ) were all constitutively expressed in the mouse macrophage cell line RAW 264 . 7 . ^^^ Crosslinking of CD 44 markedly enhanced COX 2 and weakly increased TXS mRNA , whereas COX 1 and PGES mRNA did not change significantly in these cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In anesthetized rats LPS ( 6 mg kg ( 1 ) , i . p . ) increased the expression of COX 2 as evidenced by increased circulating levels of 6 keto prostaglandin F ( 1alpha ) ( 6 keto PGF ( 1alpha ) , a stable breakdown product of PGI ( 2 ) ) , greatly exaggerated formation of 6 keto PGF ( 1alpha ) following arachidonic acid ( AA ) challenge ( 3 mg kg ( 1 ) , i . v . ) , and increased expression of COX 2 , but not COX 1 , protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results show that a low affinity for Cox 1 and a high degree of Cox 2 selectivity confers a low potential to block aspirin inhibition of platelet Cox 1 , consistent with the results of clinical studies . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Treatment with LC at levels equivalent to those found in plasma following therapeutic doses resulted in significant inhibition of both cyclooxygenase 2 ( COX 2 ) and production of 5 hydroxy eicosatetraeonic acid ( 5 HETE ) and slightly affected levels of cyclooxygenase 1 ( COX 1 ) in in vitro studies carried out on human tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To evaluate the relative contribution of cyclooxygenase 1 ( COX 1 ) and COX 2 in this process we assessed the effects of the selective COX 1 inhibitor SC 560 and the selective COX 2 inhibitor celecoxib on formalin evoked nociceptive behaviour and spinal PGE ( 2 ) release . ^^^ This suggests that the formalin evoked rapid PG release was primarily caused by COX 1 and was independent of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is hypothesized that the undesirable side effects of NSAIDs are due to the inhibition of COX 1 ( constitutive isoform ) , whereas the beneficial effects are related to the inhibition of COX 2 ( inducible isoform ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 and COX 1 proteins were determined by Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tumor growth implanted in COX 2 null mice was significantly attenuated , but not in COX 1 null or wild type mice , suggesting that COX 2 in stroma also has an important role in tumor growth . ^^^ However , NSAIDs show antitumor effects in cancer cells lacking COX 1 or COX 2 expression , and some derivatives lacking the ability to suppress COX activity show antitumor effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , a number of recent studies have raised serious questions about the two central tenets that support this approach , namely that the prostaglandins that mediate inflammation and pain are produced solely via COX 2 and that the prostaglandins that are important in gastrointestinal and renal function are produced solely via COX 1 . ^^^ So , a growing body of evidence shows that COX 2 ( not only COX 1 ) also plays a physiological role in several body functions and that , conversely , COX 1 ( not only COX 2 ) may also be induced at sites of inflammation . ^^^ Moreover , COX 2 selective NSAIDs have lost the cardiovascular protective effects of non selective NSAIDs , effects which are mediated through COX 1 inhibition ( in addition , COX 2 has a role in sustaining vascular prostacyclin production ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because polyamines are essential for neoplastic cell growth , the aim of this study was to evaluate the effect of NSAIDs ( indomethacin , a nonselective COX 1 and COX 2 inhibitor ) on polyamine metabolism in colon cancer cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compounds 3a , b and 4a , b , for which at least one of the two enantiomers had shown an inhibition value higher than 40 % in the in vivo test , were assayed for their in vitro enzymatic inhibitory activity , showing percentage inhibition values between 40 and 50 % at a concentration of 10 microM against COX 2 ; at the same concentration , they appeared to be devoid of any activity towards COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A series of 4 aryl / cycloalkyl 5 phenyloxazole derivatives was synthesized and evaluated for their ability to inhibit cyclooxygenase 2 ( COX 2 ) and cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunostaining for COX 1 , COX 2 , and PGD 2 synthase was unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The epidemiologic evidence and rodent studies suggest strongly that nonselective inhibitors of cyclooxygenase ( COX ) enzymes such as aspirin , inhibiting both COX 1 and COX 2 isoforms , reduce the incidence of and mortality from intestinal tumors . ^^^ Genetically manipulated animals show that both Cox 1 and Cox 2 disruptions decrease the tumor yield , both in genetically predisposed and in carcinogen treated mice . ^^^ The mechanisms by which COX 1 and COX 2 deficiency decrease tumorigenesis are still unknown . ^^^ However , based on the available data , we can not totally attribute the cancer preventive effects of nonsteroidal antiinflammatory drugs ( NSAIDs ) to COX 2 alone even COX 1 may have an important role in cancer prevention as suggested by the Cox 1 deficient Min mice . ^^^ It is likely that COX 1 plays a more important role in NSAID induced toxicity in humans , such as in gastric ulcer formation but inhibition of COX 2 may not be without toxic manifestations either , as suggested by the poor survival of the Cox 2 nulled mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is present in two isoforms : COX 1 ( constitutive cyclooxygenase ) which is produced in the body to maintain normal haemostatic functions , and COX 2 ( inducible cyclooxygenase ) , which is induced during inflammation in response to cytokines . ^^^ Using immunoenzymatic labelling and western blot analysis , this study has shown that both COX 1 and COX 2 were up regulated in chronic venous leg ulcers by comparison with normal human skin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As colon tumors have been shown to highly express COX 2 protein , and given , that many NSAID drugs also suppress COX 1 , it is tempting to speculate that herbal products that inhibit one or both forms of the COX enzyme will be effective agents for the prevention of cancer in man . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Four group 1 introns ( two in rnl and two in cox 1 ) and three group 2 introns ( two in nad 3 and one in cox 2 ) , two of which are trans spliced at the RNA level , reside in Mesostigma mtDNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In enzyme assay in vitro , gamma mangostin inhibited the activities of both constitutive COX ( COX 1 ) and inducible COX ( COX 2 ) in a concentration dependent manner , with the IC 50 values of about 0 . 8 and 2 microM , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
They include beta amyloid protein ; the pentraxins C reactive protein and amyloid P ; complement proteins ; the inflammatory cytokines interleukin 1 , interleukin 6 and tumor necrosis factor alpha ; the protease inhibitors alpha 2 macroglobulin and alpha 1 antichymotrypsin ; and the prostaglandin generating cyclooxygenases COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In cultured vascular smooth muscle cells , ATV reduced the expression of COX 2 mRNA induced by IL 1beta and TNF alpha without affecting COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : The gene expressions of COX 1 and COX 2 during acute hypoxia were measured with semi quantified RT PCR in the 2nd , 4th and 6th subculture of intrapulmonary artery smooth muscle cells ( PASMC ) of wistar rats under normoxic and continuous hypoxic condition separately . ^^^ RESULTS : In all three generations , the expressions of COX 1 had no significant changes in hypoxia , while the COX 2 mRNA expression was higher in chronic hypoxic group than that in normoxic group and elevated with the duration of hypoxia exposure . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoenzymes of cyclooxygenase ( COX ) , the key enzyme in prostaglandin ( PG ) biosynthesis , COX 1 and COX 2 , have been identified . ^^^ COX 1 was proposed to regulate physiological functions , COX 2 to mediate pathophysiological reactions such as inflammation . ^^^ However , concurrent treatment with a COX 1 and a COX 2 inhibitor induces severe gastric damage . ^^^ This indicates that in normal mucosa both COX 1 and COX 2 have to be inhibited to evoke ulcerogenic effects . ^^^ In the acid challenged rat stomach inhibition of COX 1 alone is associated with dose dependent injury which is aggravated by additional inhibition of COX 2 activity or prevention of acid induced up regulation of COX 2 expression by dexamethasone . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
With the availability of celecoxib and rofecoxib , 2 cyclooxygenase ( COX 2 ) inhibitors ( or COX 1 sparing agents ) as new forms of NSAIDs , these issues have become magnified not only in the context of risk to benefit ratios but also interms of pharmacoeconomics because they have been proven to be equally efficacious as the nonselective NSAIDs , with an improved safety profile particularly within the gastrointestinal tract , but at a significantly increased cost . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The ability of these agents to cause adverse effects are also known , and the search for newer NSAIDs with less side effects accelerated after the two isoforms of cyclooxygenase ( COX ) ( COX 1 and COX 2 ) were discovered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) product prostaglandin ( PG ) E 2 appears to be central to this process , however , non selective inhibition of COX activity with non steroidal anti inflammatory agents that block both the constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms of cyclooxygenase has not yielded promising results in trauma patients . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The recognition of two COX isoforms , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) , both suppressed by traditional NSAIDs , has led to an expanded hypothesis of NSAID action which consists of two postulates , namely , the efficacy of NSAIDs in the treatment of arthritis is due to the suppression of COX 2 , while much of the toxicity associated with non selective NSAIDs is the consequence of COX 1 suppression . ^^^ In this report , the published experience with selective COX 2 inhibitors in the treatment of mechanical and inflammatory arthropathies is reviewed to examine the premise that isolated COX 2 suppression is comparable in efficacy to the dual COX 1 / COX 2 suppression produced by non selective NSAIDs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Until now , the expression pattern of isoforms cox 1 and cox 2 of cyclooxygenase in bovine cumulus oocyte complexes ( COCs ) was unknown . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists in two related but unique isoforms , COX 1 and COX 2 , and is suggested to have specific functions in different segments of the nephron . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase ( COX ) isoforms have been identified : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Experiments were conducted to determine the effects of novel anti neoplastic isochalcones ( DJ compounds ) , on cyclooxyegenase 1 and 2 ( COX 1 and COX 2 ) enzyme expression in androgen receptor dependent human prostate cancer cell line LNCaP . ^^^ Results from Western blot analysis and cell flow cytometry showed that DJ 52 and DJ 53 decreased the steady state levels of COX 1 and COX 2 protein levels in a dose dependent manner . ^^^ In this study , we report that novel isochalcones decreased COX 1 , COX 2 and EGF levels as well as LNCaP cellular growth in a dose responsive manner . ^^^ Our findings indicate that relative decreases in COX 1 , COX 2 and EGF expressions might serve as indicators of tumor growth inhibition in prostate neoplasms . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Involvement of constitutive ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) in the adrenergic induced ACTH and corticosterone secretion . ^^^ The involvement of prostaglandins synthesized by constitutive ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) in central stimulation of the hypothalamic pituitary adrenal ( HPA ) axis by adrenergic receptor agonists was investigated in conscious rats . ^^^ COX 1 and COX 2 inhibitor , piroxicam ( 0 . 02 and 0 . 2 microg ) and compound NS 398 ( 0 . 01 and 0 . 1 microg ) , respectively , were given intracerebroventricularly ( i . c . v . ) 15 min prior to i . c . v . adrenergic receptor agonists : phenylephrine ( 30 microg ) and clonidine ( 10 microg ) , an alpha 1 and alpha 2 adrenergic agonist , and isoprenaline ( 20 microg ) a non selective beta adrenergic agonist and clenbuterol ( 10 microg ) a selective beta 2 adrenergic agonist . ^^^ COX 1 participates considerably and COX 2 markedly in the potent stimulatory action of selective beta 2 adrenergic receptors on HPA axis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of social stress on COX 1 and COX 2 induced alterations in the adrenergic agonists evoked hypothalamic pituitary adrenal responses . ^^^ The purpose of the present study was to investigate the contribution of prostaglandins ( PGs ) synthesized by constitutive ( COX 1 ) and inducible ( COX 2 ) cyclooxygenase to stimulation of the hypothalamic pituitary adrenal ( HPA ) axis by adrenergic receptor agonists in rats under social crowing stress 3 days , ( 21 per a cage for 6 ) animals . ^^^ The effects of phenylephrine , clonidine and isoprenaline , an alpha 1 , alpha 2 and beta adrenergic agonist , respectively , in the presence and absence of COX 1 inhibitor , piroxicam , and COX 2 inhibitor , compound NS 398 , on ACTH and corticosterone secretion in stressed rats were compared with these effects in non stressed animals . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the face of pending injury such as intragastric acid a COX 1 inhibitor evokes dose dependent damage whereas COX 2 inhibitors are not injurious as long as the function of afferent nerves is not impaired . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Endothelial cell mRNAs encoding cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , prostaglandin synthase ( PGS ) , and thromboxane synthase ( TXS ) were measured by quantitative real time RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Radiosynthesis , in vitro validation , and in vivo evaluation of 18F labeled COX 1 and COX 2 inhibitors . ^^^ In this article , we describe the radiosynthesis and evaluation of 18F labeled cyclooxygenase ( COX ) inhibitors . 18F SC 63217 is selective to COX 1 and has a COX 1 inhibitory concentration of 50 % ( IC ( 50 ) ) < 10 nmol / L and a COX 2 IC ( 50 ) > 100 micromol / L . 18F SC 58125 has IC ( 50 ) values of > 100 micromol / L ( COX 1 ) and < 86 nmol / L ( COX 2 ) . ^^^ Higher levels of 18F SC 58125 were observed in the kidney , an organ known to contain high levels of COX 2 rather than COX 1 . 18F SC 58125 was retained in brain tissue . ^^^ CONCLUSION : We have developed a radiosynthetic route that can yield 18F labeled selective inhibitors of COX 1 or COX 2 . ^^^ Our results indicate that 18F SC 58125 has potential as a marker of COX 2 activity but that , because of high nonspecific binding , 18F SC 63217 was not a good choice as a marker of COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to compare the efficacy and safety of the COX 1 sparing , COX 2 specific inhibitor , celecoxib , with the conventional NSAID naproxen , and placebo , in the treatment of OA of the hip . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since the pharmacological profiles of various non steroidal anti inflammatory drugs ( NSAIDs ) might depend on their differing selectivity for cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) , we developed a new screening method using human peripheral monocytes . ^^^ Monocytes without LPS stimulation exclusively expressed COX 1 on Western blotting analysis , whereas LPS stimulation induced COX 2 expression . ^^^ Unstimulated monocytes ( COX 1 ) and LPS stimulated monocytes ( COX 2 ) were then used to determinethe COX selectivity of various NSAIDs . ^^^ The percentage inhibition of COX 1 activity at the IC 50 of COX 2 also showed a wide variation among these NSAIDs . ^^^ The bioassay system using human monocytes to assess the inhibitory effects of various NSAIDs on COX 1 and COX 2 may become a clinically useful screening method . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 mediates electrolyte and fluid secretion induced by a number of peptide hormones , including bradykinin , angiotensin , and endothelin , via local formation of prostaglandin ( PG ) E 2 ; however , the physiological role of COX 2 remains largely unknown . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas many of the side effects of nonsteroidal anti inflammatory drugs ( NSAIDs ) ( e . g . , gastrointestinal ulceration and bleeding , platelet dysfunctions ) are caused by a suppression of COX 1 activity , inhibition of COX 2 derived prostanoids facilitates the anti inflammatory , analgesic , and antipyretic effects of NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Rats undergoing balloon angioplasty of the carotid artery were randomized to receive a selective COX 2 inhibitor ( SC 236 ) , a selective COX 1 inhibitor ( SC 560 ) or a combination of the two . ^^^ Normal , uninjured vessels showed COX 1 , but no COX 2 expression . ^^^ Fourteen days after balloon injury , both COX 1 and COX 2 were expressed in the neointima . ^^^ Both the COX 1 inhibitor SC 560 and the COX 2 inhibitor SC 236 suppressed the generation of PGE ( 2 ) and PGF ( 2alpha ) , particularly when combined , suggesting a role for both isozymes in the generation of prostaglandins in this model . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms , COX 1 and COX 2 , have been identified . ^^^ Both COX 1 and COX 2 are highly expressed in the kidney and both are inhibited by conventional NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Intrathecal phospholipase A 2 ( PLA 2 ) and cyclooxygenase 2 ( COX 2 ) , but not COX 1 , inhibitors attenuate facilitated pain states generated by peripheral injury / inflammation and by direct activation of spinal glutamate and substance P receptors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we have analyzed the expression of COX 1 and COX 2 in glioma cell lines and biopsies of glial tumors . ^^^ In normal glia no expression of both COX isoforms was present , however , reactive astrocytes and glial tumors of all grades demonstrated expression of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 expression in all carcinoma tissues was associated with enhanced expression of COX 2 RNA and protein . ^^^ Overexpression of COX 1 in HeLa cells resulted in induced expression of cyclooxygenase 2 ( COX 2 ) and prostaglandin E synthase ( PGES ) concomitant with increased prostaglandin E ( 2 ) ( PGE ( 2 ) ) synthesis . ^^^ Treatment of HeLa cells overexpressing COX 1 with the dual COX enzyme inhibitor indomethacin or selective COX 2 inhibitor NS 398 significantly reduced PGE ( 2 ) synthesis . ^^^ Indomethacin , but not NS 398 , treatment abolished the up regulation of expression of COX 2 and PGES in HeLa cells , suggesting that the observed up regulation of COX 2 and PGES was mediated by COX 1 enzyme products . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme have been identified : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) inhibitors ( flurbiprofen , ketoprofen and ketrolack ) attenuated the nicotine induced contraction in a concentration dependent manner , and cyclooxygenase 2 ( COX 2 ) inhibitors at high concentrations ( nimesulide and NS 389 ) slightly attenuated the contraction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biological evaluation suggested that 3a and 3b are reversible inhibitors of COX 1 and irreversible inhibitors of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The synthesis of these mediators depends on two isoforms of cyclooxygenase ( COX ) , constitutive COX 1 and inducible COX 2 . ^^^ The sensitized animals showed a robust and transient induction of COX 2 mRNA expression within 1 h after ovalbumin challenge , whereas their COX 1 mRNA levels remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two COX isoforms have been identified , COX 1 and COX 2 . ^^^ In many situations , the COX 1 enzyme is produced constitutively ( e . g . , in gastric mucosa ) , whereas COX 2 is highly inducible ( e . g . , at sites of inflammation and cancer ) . ^^^ This review summarizes our current understanding of the role of COX 1 and COX 2 in normal physiology and disease . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MODE OF ACTION : NSAID have a common effect , inhibiting the production of prostanoids via reduced activity of two cyclo oxygenases ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since the discovery of two PG synthesising enzymes , COX 1 and COX 2 , and the substantial evidence that sparing COX 1 is advantageous for gastric safety , great interest has focused on selective COX 2 inhibitors . ^^^ However , the older drugs etodolac , nimesulide and meloxicam , made before COX 2 was discovered , are also COX 1 sparing and have good GI safety and therapeutic activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We studied the expression of both Cox 1 and Cox 2 by immunohistochemistry in 29 transitional cell carcinomas of the urinary bladder . ^^^ No correlation was detected between Cox 1 or Cox 2 expression and tumour differentiation or stage of invasion . ^^^ We also evaluated the mRNA expression of Cox 1 and Cox 2 and synthesis of prostaglandin E 2 ( PGE 2 ) in three bladder carcinoma cell lines ( RT 4 , 5637 , and T 24 ) . ^^^ All cell lines expressed high levels of Cox 2 mRNA , whereas Cox 1 mRNA expression was detected only in T 24 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All the compounds tested gave good COX 1 and moderate COX 2 enzyme inhibitory activities at 100 microg / mL . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using COX isoform selective pharmacological inhibitors and gene knockout mice , we found that COX 2 inhibition during LPS induced inflammation results in preserved food intake and maintenance of body weight , whereas COX 1 inhibition results in augmented and prolonged weight loss . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using an ex vivo rat whole blood assay , FR 122047 ( 0 . 032 3 . 2 mg kg ( 1 ) ) inhibited COX 1 derived thromboxane ( TX ) B ( 2 ) production with ED ( 50 ) value of 0 . 059 mg kg ( 1 ) , indicating that it was orally active , but did not inhibit lipopolysaccharide induced prostaglandin ( PG ) E ( 2 ) production derived by COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The copy numbers of cDNA for COX 1 and COX 2 were standardized to glyceraldehyde 3 phosphate dehydrogenase from the same sample . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both pedunculariside and agnuside showed preferential inhibition of COX 2 , with IC 50 values of 0 . 15 + / 0 . 21 mg / ml and 0 . 026 + / 0 . 015 mg / ml respectively , while having only small inhibitory effects on COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our results indicate a dissociation between the anti inflammatory and the anti hyperalgesic activity of NSAIDs , where the latter seems to be more evident after the block of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Only the glycosidic phenylpropanoid esters showed an inhibitory activity towards the Cox 2 enzyme and three of them : acteoside 2 , forsythoside B 3 , arenarioside 4 , exhibited higher inhibitory potencies on Cox 2 than on Cox 1 . ^^^ These results are of interest , as Cox 2 is mainly associated with inflammation and the Cox 1 inhibition with adverse side effects often observed with non steroidal anti inflammatory drugs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We measured the level of prostaglandin E 2 ( PGE 2 ) production by DGF and NDGF by radioimmunoassay , and also measured the mRNA expression of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) by using the real time PCR method . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin E 2 ( PGE 2 ) increases intracellular cAMP levels and stimulates estrogen biosynthesis , and our recent studies have shown a strong linear association between CYP 19 expression and the sum of COX 1 and COX 2 expression in breast cancer specimens . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Serial sections were obtained and a standard three layer immunohistochemistry protocol , using COX 1 and COX 2 specific mouse monoclonal antibodies , applied . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is known that two forms of cyclooxygenase exist : cyclooxygenase 1 ( COX 1 ) playing house keeping functions and cyclooxygenase 2 ( COX 2 ) involved in inflammatory responses . ^^^ Synovial tissues from patients with RA are shown to contain COX 2 and to a less extent COX 1 . ^^^ The understanding of crucial role of COX 2 in synovial inflammation led to development of new group of anti inflammatory agents selective COX 2 inhibitors , that inhibit specifically COX 2 , providing effective anti inflammatory action without the side effects associated with inhibition of COX 1 . ^^^ In the context of widespread use of selective COX 2 inhibitors hypothetical role of COX 1 in RA pathology should be elucidated . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dipyrone at a very high concentration ( 10 mM ) inhibited only COX 1 , while indomethacin ( 0 . 1 microM ) blocked COX 1 and COX 2 in COS 7 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two COX enzymes have been identified : a constitutively expressed COX 1 and an inducible , highly regulated COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Similarly , PGI 2 production and COX 2 expression were significantly lower in vascular smooth muscle cells of SHRSP than WKY , whereas there was no difference in the COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The majority of NSAIDs inhibit either COX 1 , COX 2 , or both and exert their anti COX , anti inflammatory , and anti tumorigenic effects in vivo in a parallel dose dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We also observed that the growth of COX 1 ( / ) cells was significantly retarded compared to wild type ( WT ) and COX 2 deficient ( COX 2 ( / ) ) cells . ^^^ In this study , COX 2 expression and its promoter activity were compared in immortalized , nontransformed fibroblasts from WT , COX 1 ( / ) or COX 2 ( / ) mice in the context of the role of COX 2 as a growth regulator . ^^^ When compared with WT cells expressing both COX isoenzymes , constitutive COX 2 protein and promoter activity were significantly higher in COX 1 ( / ) cells as determined by Western blotting and luciferase assays using a 5 ' flanking promoter construct of the murine COX 2 gene . ^^^ The luciferase assay using a series of luciferase linked COX 2 promoter deletions transfected into COX 1 ( / ) cells indicated that a region involving NF kappaB plays a significant role in regulating constitutive COX 2 expression . ^^^ Data from electrophoretic mobility shift assays showed that COX 1 ( / ) cells contained higher levels of activated NF kappaB than either WT or COX 2 ( / ) cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Isolates were evaluated for their inhibitory effects against both cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) and in a mouse mammary organ culture assay . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , selective inhibition of COX 2 , but not COX 1 , was followed by significant decrements in PGE ( 2 ) and IL 10 , a concomitant restoration of IL 12 production , and an enhancement of DC stimulatory potential . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs may not only act on COX 2 but also inhibit COX 1 activity or activate peroxisome proliferator activated receptor gamma ( PPAR gamma ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since PG synthesis is mediated by cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) , the present study was designed to examine which COX isoform is involved in this phenomenon . 2 . ^^^ Renal COX 1 and COX 2 protein expression and distribution were analysed by Western blot and immunohistochemistry in nine rats with carbon tetrachloride induced cirrhosis and ascites and 10 control animals . ^^^ The effects of placebo and selective COX 1 ( SC 560 ) and COX 2 ( celecoxib ) inhibitors on urine flow ( 5 ) , urinary excretion of sodium ( U ( Na ) 5 ) and PGE ( 2 ) ( U ( PGE 2 ) 5 ) , glomerular filtration rate ( GFR ) , renal plasma flow ( RPF ) , the diuretic and natriuretic responses to furosemide and renal water metabolism were assessed in 88 rats with cirrhosis and ascites . 3 . ^^^ These results indicate that despite abundant renal COX 2 protein expression , the maintenance of renal function in cirrhotic rats is mainly dependent on COX 1 derived prostaglandins . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using selective COX inhibitors , we examined whether inhibition of COX 1 or COX 2 alone is sufficient for induction of intestinal damage in rats . ^^^ However , the combined administration of COX 1 and COX 2 inhibitors provoked intestinal damage with an incidence of 100 % . ^^^ These results suggest that the intestinal ulcerogenic property of NSAID is not accounted for solely by inhibition of COX 1 and requires inhibition of COX 2 as well . ^^^ The inhibition of COX 1 up regulates COX 2 expression , and this may be a key to NSAID induced intestinal damage . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Production of thromboxane B 2 ( TXB 2 ) during clotting and of prostaglandin E 2 ( PGE 2 ) during endotoxin exposure served as indicators of platelet COX 1 and monocyte COX 2 activity , respectively . ^^^ RESULTS : Intra subject variation for COX 1 and COX 2 at baseline was at 26 + / 18 % and 18 + / 13 % respectively , and intersubject variation at 39 % and 36 % , respectively . ^^^ The ratios of IC50s and , at best , of IC80s revealed diclofenac and meloxicam as selective COX 2 inhibitors and ibuprofen as a preferential COX 1 inhibitor in vitro . ^^^ However , after oral intake , ibuprofen inhibited ex vivo COX 2 by 80 % whereas diclofenac inhibited COX 1 by 70 % . ^^^ Using in vitro dose response curves , the in vivo inhibitory potency of diclofenac was estimated adequately from its circulating concentration ( [ 0 . 18 , 0 . 21 ] for COX 1 and [ 0 . 13 , 0 . 03 ] for COX 2 ) but this was not the case for ibuprofen on COX 2 ( [ 0 . 14 , 0 . 27 ] ) and meloxicam on COX 1 ( [ 0 . 31 , 1 . 05 ] ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This was increased by the addition of IL 1beta , to 152 . 1 + / 43 . 0 pg / mg protein after a 24 h incubation ; the expression of cyclooxygenase 2 ( COX 2 ) protein was also increased , but there was no effect on the expression of COX 1 and TXA 2 synthase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins ( PGs ) , bioactive lipid molecules produced by cyclooxygenase enzymes ( COX 1 and COX 2 ) , have diverse biological activities , including growth promoting actions on gastrointestinal mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Heme and products derived from its metabolism potentially influence renal function and blood pressure by affecting the expression and / or activity of hemeproteins , including cytochrome P 450 ( CYP4A ) monooxygenases and cyclooxygenases ( COX 1 and COX 2 ) . ^^^ SnCl ( 2 ) treatment did not affect COX 1 expression but markedly reduced cortical and medullary COX 2 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Samples were taken at corresponding time points for detection of synovial COX 1 , COX 2 and inducible nitric oxide synthase ( iNOS ) mRNA , and measurement of urinary prostaglandin ( PG ) and nitric oxide metabolites ( NO ( 10 ) ) . ^^^ COX 1 mRNA was detectable at all time points ; COX 2 mRNA only at 3 h . ^^^ COX 1 but not COX 2 contributes to the maintenance of basal blood flow in the hyperaemic joint at 24 h . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study aimed to provide some insight into the relative contributions of the constitutive and inducible forms of cyclooxygenase ( COX 1 and COX 2 ) to the generation of these prostanoids by examining the effects of ( 1 ) endotoxin treatment on the expression of COX 1 and COX 2 mRNAs in the various components of the HPA axis in control and glucocorticoid pretreated rats , and ( 2 ) selective inhibition of COX 2 on the production of corticosterone by adrenal tissue in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 , unlike the constitutively expressed COX 1 , is an inducible enzyme upregulated during cell proliferation and inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Celecoxib and rofecoxib are selective cyclooxygenase 2 ( COX 2 ) inhibitors which possess the same anti inflammatory and analgesic activities , but a better gastric tolerability compared to the non selective COX 1 and COX 2 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the anti inflammatory screening , the dichloromethane and hexane extracts of S . natalensis resulted in good inhibition against both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Esophageal ulceration triggered increases in : esophageal epithelial cell proliferation ; expression of COX 2 ( but not COX 1 ) ; hepatocyte growth factor ( HGF ) and its receptor , c Met ; and activation of extracellular signal regulated kinase 2 ( ERK 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin PGE ( 2 ) increases intracellular cAMP levels and stimulates estrogen biosynthesis , and our recent studies have shown a strong linear association between CYP 19 expression and the sum of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) expression in breast cancer specimens . ^^^ Untreated normal adipose stromal cells exhibited high basal levels of COX 1 but low to undetectable levels of COX 2 . ^^^ In summary , the results of this investigation on the effects of several paracrine and / or autocrine signaling pathways in the regulation of expression of aromatase , COX 1 , and COX 2 in breast cells has identified more complex relationships . ^^^ Furthermore , increased secretion of prostaglandins such as PGE ( 2 ) from constitutive COX 1 and inducible COX 2 isozymes present in epithelial and stromal cell compartments will result in both autocrine and paracrine actions to increase aromatase expression in the tissues . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A serious side effect of COX 1 and COX 2 is renal damage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Rofecoxib , a COX 2 specific NSAID , does not inhibit the COX 1 enzyme , thereby decreasing the potential for gastrointestinal related adverse effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have examined the role of peripheral prostaglandins synthesized by cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in inflammatory pain using the PIFIR model . ^^^ Rofecoxib ( a selective COX 2 inhibitor ) and SC 560 ( a selective COX 1 inhibitor ) both produced dose dependent effects . ^^^ The inhibition of both COX 1 and COX 2 produced a more profound analgesic effect than the inhibition of either COX 1 or COX 2 alone . ^^^ Thus , it could be expected that inhibition of both COX 1 and COX 2 is required for non steroidal anti inflammatory drugs ( NSAID ) induced antinociception in the rat . ^^^ These findings suggest that the therapeutic effects of NSAIDs may involve , at least in part , inhibition of COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A series of 4 ( 4 cycloalkyl / aryl oxazol 5 yl ) benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase 2 ( COX 2 ) and cyclooxygenase 1 ( COX 1 ) enzymes . ^^^ Most substituents reduced or lost both COX 2 and COX 1 activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase , the rate limiting enzyme in prostaglandin synthesis , is expressed in constitutive ( COX 1 ) and inducible ( COX 2 ) isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAIDs ) are nonselective inhibitors of cyclooxygenase ( COX ) isoforms COX 1 and COX 2 . ^^^ Thus , selective COX 2 inhibitors , or coxibs , were designed to inhibit only the production of COX 2 dependent inflammatory prostaglandins , without any effect on COX 1 and its gastroprotective function . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Development was based on the hypothesis that COX 1 is the housekeeping enzyme necessary for production of prostaglandins ( PGs ) with homeostatic functions , whereas COX 2 is a mediator of pathophysiologic processes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because prostaglandins ( PGs ) and nitric oxide ( NO ) have been proposed to be involved in angiogenesis in vivo , the production of PGs and NO and the behavior of inducible NO synthase ( iNOS ) , cyclooxygenase 1 ( COX 1 ) , and inducible cyclooxygenase ( COX 2 ) were studied in parental drug sensitive ( P 5 ) liver cancer cell lines and in P 5 derived MDR 1 cells P 1 ( 0 . 5 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two forms of COX have been identified : COX 1 , which is constitutively expressed , and COX 2 , which is an inducible enzyme . ^^^ To define the role of COX 1 in nociceptive transmission , we examined the effect of oral and intrathecal administration of 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ( SC 560 ) , a selective COX 1 inhibitor , on the rat formalin test and compared the effect of SC 560 with that of celecoxib , a COX 2 selective inhibitor , and indomethacin , a nonselective COX 1 and COX 2 inhibitor , on the rat formalin test . ^^^ These data suggest that prostaglandins synthesized by COX 1 are not involved in nociceptive transmission during the rat formalin test but that COX 2 does play an important role in the rat formalin test . ^^^ IMPLICATIONS : Our data suggest that a COX 2 selective inhibitor , but not a COX 1 selective inhibitor , may produce a good analgesic effect on the inflammatory pain state in a clinical situation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In these experiments , the significance of the COX isoforms cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in post training memory processes was assessed . ^^^ After the completion of training , rats received an intraperitoneal injection of the nonselective COX inhibitor indomethacin , the COX 1 specific inhibitor piroxicam , the COX 2 specific inhibitor N [ 2 cyclohexyloxy 4 nitrophenyl ] methanesulfonamide ( NS 398 ) , vehicle ( 45 % 2 hydroxypropyl beta cyclodextrin in distilled water ) , or saline . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : To evaluate its utility as an intermediate biomarker in bronchial chemoprevention trials , the authors examined Cox 1 and Cox 2 expression in normal and premalignant bronchial epithelial cells and nonsmall cell lung carcinoma ( NSCLC ) samples using an immunohistochemical staining technique . ^^^ RESULTS : In the normal bronchial epithelium , Cox 2 expression was found to be completely negative whereas Cox 1 expression was noted in a few scattered cells . ^^^ There were relatively more Cox 2 positive tumors , as defined by positive staining in > 10 % of tumor cells , than Cox 1 positive tumors ( 30 of 101 tumors [ 30 % ] vs . 14 of 101 tumors [ 14 % ] ; P = 0 . 01 ) . ^^^ Although smokers tended to have more Cox 2 positive tumors than nonsmokers ( 29 of 91 tumors in the smokers [ 32 % ] vs . 1 of 10 tumors in the nonsmokers [ 10 % ] ; P = 0 . 15 ) , there was no statistically significant relation found between Cox 1 or Cox 2 expression and smoking status or prognostically significant clinicopathologic features . ^^^ CONCLUSIONS : The results of the current study suggest that Cox 1 and Cox 2 expression may not be a useful intermediate biomarker in bronchial chemoprevention trials . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme , cyclo oxygenase 1 ( COX 1 ) and COX 2 , have been identified . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dihydrokawain ( 1 ) and yangonin ( 6 ) showed the highest COX 1 and COX 2 inhibitory activities at 100 microg / ml , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , existing as the COX 1 and COX 2 isoforms , converts arachidonic acid to prostaglandin H 2 , which is then further metabolized to various prostaglandins . ^^^ In HUVEC treated with VEGF ( 0 . 01 50 ng / ml ) , COX 2 protein , but not COX 1 , and COX activity were increased in a dose dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several commercially available C 8 to C 24 saturated and unsaturated fatty acids ( 1 29 ) were assayed for cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibitory and antioxidant activities . ^^^ The highest inhibitory activities among the saturated fatty acids tested on cyclooxygenase enzymes COX 1 and COX 2 were observed for decanoic acid to lauric acid ( 3 5 ) at 100 microg mL ( 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The reason for this difference is not known , but it might be related to the fact that ketoprofen and diclofenac belong to different NSAID subgroups and have a different selectivity for the two cyclo oxygenases COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : Pretreatment induced COX 2 , in addition to COX 1 , seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To assess this compensatory expression phenomenon in vivo , we quantified COX 1 and COX 2 mRNA levels in various organs of COX 1 and COX 2 ablated mice using a reverse transcriptase polymerase chain reaction ( RT PCR ) method . ^^^ We found that COX 1 and COX 2 mRNAs in the brains of COX ablated mice were elevated > 2 fold compared with wild type ( WT ) animals . ^^^ COX 2 mRNA was enhanced approximately 2 fold in the kidneys and stomachs of COX 1 deficient mice while COX 1 expression remained unchanged . ^^^ Conversely , the livers of COX 2 deficient mice expressed 15 fold higher COX 1 mRNA levels , while hepatic COX 2 mRNA levels were not significantly altered in the COX 1 ablated mice . ^^^ Steady state levels of COX 1 and COX 2 mRNAs in the hearts , lungs and spleens of WT , COX 1 and COX 2 deficient mice were indistinguishable from each other . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms , COX 1 and COX 2 , both of which are constitutively expressed in the central nervous system ( CNS ) . ^^^ Studies have shown that COX 1 and COX 2 are involved in physiological and pathological conditions of the brain . ^^^ COX 2 activity was inhibited with a COX 2 selective drug , celecoxib ( Celebrex ) , and COX 1 was antagonized with SC 560 . ^^^ We found that inhibition of COX 2 led to decreased viral titers , while COX 1 antagonism did not have the same effect at day 1 post infection . 5 lipooxygenase ( 5 LO ) expression and neutrophil recruitment in the CNS were increased in celecoxib inhibited mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
DGLA and AA had similar affinities ( K ( m ) values ) and maximal reaction rates ( 5 ( max ) ) for cyclo oxygenase 2 ( COX 2 ) , whereas AA was metabolized preferentially by cyclo oxygenase 1 ( COX 1 ) . ^^^ It appears that employing a dietary or a combined dietary / pharmacological paradigm to augment the cellular ratio of DGLA / AA is not an effective route to enhance endogenous synthesis of PGE ( 1 ) over PGE ( 2 ) , at least in cells / tissues where COX 1 predominates over COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The role of COX 1 and COX 2 in asthma pathogenesis and its significance in the use of selective inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This finding is similar to earlier observations of an accelerated non synonymous substitution rate for some lineages of primates for COX 1 , COX 2 , COX 4 , and COX7AH . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is the crucial enzyme for synthesis of prostaglandins and occurs in two isoforms COX 1 and COX 2 . ^^^ Whilst COX 1 is constantly expressed in the gastrointestinal tract in large quantities and probably maintains mucosal integrity through constant generation of prostaglandins , COX 2 is induced principally during inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme COX 1 and COX 2 are known to exist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the key enzyme in transforming AA into PGs , has two isoforms : COX 1 is constitutively expressed , and COX 2 , is inducible . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TGF beta 1 , TGF beta 2 , COX 1 and COX 2 protein levels were assessed in the platelets by Western blot analysis . ^^^ Piroxicam in the presence of high corn oil ( HFC+P ) significantly lowered the level of COX 2 ( p < 0 . 001 ) , without having any effect on COX 1 level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonselective cyclooxygenase ( COX ) inhibition during allergic sensitization with ovalbumin in a murine model leads to an increase in the Type 2 cytokines interleukin 5 ( IL 5 ) and IL 13 ; however , the effect of selective COX 1 and COX 2 inhibitors on these cytokines is unknown . ^^^ Expression of COX 1 protein did not increase with ovalbumin sensitization , but expression of COX 2 protein did . ^^^ Ovalbumin sensitized mice treated with either selective COX 1 inhibitor SC 58560 ( OVA COX 1 inhibitor ) or selective COX 2 inhibitor SC 58236 ( OVA COX 2 inhibitor ) had significantly greater airway hyperresponsiveness ( p < 0 . 05 ) and higher levels of IL 13 ( p < 0 . 05 ) in lung supernatants than did untreated mice that were ovalbumin sensitized ( OVA ) . ^^^ We conclude that in the BALB / c mouse , COX inhibition with either a COX 1 or COX 2 inhibitor during allergen sensitization augments production of IL 13 and increases airway hyperresponsiveness . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoenzymes of COX have been identified ; COX 1 and COX 2 . ^^^ Whereas COX 1 is expressed constitutively in most tissues and responsible for tissue homeostasis , COX 2 is inducible and plays an important role in inflammation and intestinal tumorigenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recovery of ischaemic injured porcine ileum : evidence for a contributory role of COX 1 and COX 2 . ^^^ However , the relative role of COX 1 and COX 2 elaborated prostaglandins in this process is unclear . ^^^ AIMS : To assess the role of COX 1 and COX 2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX 1 and COX 2 inhibitors on mucosal recovery and eicosanoid production . ^^^ Injured tissues treated with the selective COX 1 inhibitor SC 560 ( 5x10 ( 6 ) M ) or the COX 2 inhibitor NS 398 ( 5x10 ( 6 ) M ) recovered to control levels of resistance within three hours , associated with significant elevations of PGE and 6 keto PGF1alpha compared with untreated tissues . ^^^ CONCLUSIONS : The results suggest that recovery of resistance is triggered by PGE and PGI 2 , which may be elaborated by either COX 1 or COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of COX 2 has been associated with the therapeutic effects of NSAIDs , whereas inhibition of COX 1 is believed to be the cause of the adverse gastrointestinal effects associated with NSAID therapy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using a highly metastatic mammary tumor cell line that expresses both cyclooxygenase ( COX ) isoforms , we now show that oral administration of either a selective COX 2 inhibitor ( celecoxib ) or a selective COX 1 inhibitor ( SC 560 ) to mice with established tumors results in significant inhibition of tumor growth . ^^^ Metastatic capacity is also reduced by treatment of tumor bearing mice with either COX 1 or COX 2 selective inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Male Sprague Dawley rats were infused with furosemide ( 12 mg / kg per d ) for 6 d , and the expression of cyclooxygenase 1 and 2 ( Cox 1 and Cox 2 ) was analyzed in the different kidney zones . ^^^ Furosemide increased Cox 2 mRNA expression approximately twofold in the cortex , but it left Cox 1 mRNA expression unaltered there . ^^^ In the outer medulla , furosemide changed neither Cox 1 nor Cox 2 mRNA expression . ^^^ In the inner medulla , however , furosemide decreased Cox 1 and Cox 2 mRNA levels to approximately 30 % and 60 % of their control levels , respectively . ^^^ To investigate the influence of the osmolarity on the expression of Cox and the production of PGE ( 2 ) under defined in vitro conditions , inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol / L to 600 mmol / L , and Cox 1 and Cox 2 mRNA abundance were determined after 24 h an 48 h . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot was performed to measure the level of COX 1 , COX 2 , p 65 , p 50 , and 1 B proteins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This is the first report showing the potential cancer chemopreventive activity of trans astringin , a plant stilbenoid recently found in wine . trans Astringin and its aglycone trans piceatannol were active in the mouse mammary gland organ culture assay but did not exhibit activity in COX 1 and COX 2 assays . trans Resveratrol was active in all three of the bioassays used in this investigation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : The expression of cPLA 2 and COX 1 and COX 2 mRNAs was detected in all samples examined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : The findings that inducible cyclooxygenase ( COX ) 2 , but not constitutive COX 1 , is upregulated in the brain of conscious rats approximately 1 . 5 h after intraperitoneal pyrogen administration , that the systemic administration of COX 2 inhibitors abolishes fever , and that COX 2 deficient mice do not develop fever in response to intraperitoneal lipopolysaccharide ( LPS ) have strongly implicated COX 2 in the mediation of the febrile response . ^^^ It consequently seems improbable that inducible COX 2 could play a role in the initiation of this febrile response , but a role for COX 1 has not yet been categorically ruled out ; or , alternatively , a constitutive isoform of COX 2 could have such a role . ^^^ We have studied , therefore , the effects of the non selective COX inhibitor indomethacin , the COX 1 selective inhibitor SC 560 , and the COX 2 selective inhibitor nimesulide on the characteristically biphasic fever induced by intravenous LPS in conscious guinea pigs ; it has an onset latency of approximately 10 min . ^^^ CONCLUSIONS : COX 1 is not involved in intravenous LPS fever production , and COX 2 appears to play a greater role in the late than in the early phase of intravenous LPS fever in guinea pigs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 mRNA was detected after exposure to stress in both the light and dark phases . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Up regulation of COX 2 by inhibition of COX 1 in the rat : a key to NSAID induced gastric injury . ^^^ However , the role of COX 1 or COX 2 inhibition in the pathogenisis of these lesions remains unclear . ^^^ AIM : To examine the gastric ulcerogenic properties of selective COX 1 and COX 2 inhibitors in rats and to investigate further the relationship of COX inhibition to various events involved in the process of NSAID induced gastric lesions . ^^^ The normal gastric mucosa expressed COX 1 mRNA and not COX 2 mRNA , but COX 2 mRNA was expressed in the stomach after administration of SC 560 as well as indomethacin but not rofecoxib . ^^^ CONCLUSION : These results suggest that the gastric ulcerogenic properties of NSAIDs are not accounted for solely by COX 1 inhibition , but require the inhibition of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
E ( 2 ) ( 10 ( 8 ) M for 15 min ) caused a 52 % increase in PGI ( 2 ) , the threshold concentration was 10 ( 10 ) M E ( 2 ) , the effect occurred within 5 min , and it was not related to changes in cyclooxygenase type 1 ( COX 1 ) or COX 2 abundance . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 were shown to be expressed in platelets from patients undergoing a coronary artery bypass graft . ^^^ There was a significant increase in COX 2 expression at day 5 as compared with pre surgery values ( mean fluorescence 12 . 31 + / 0 . 88 versus 9 . 15 + / 0 . 88 ; means + / SEM , n = 7 , P < 0 . 05 ) , whereas COX 1 levels did not change ( 13 . 45 + / 1 . 11 versus 12 . 38 + / 1 . 41 ; n = 7 , P > 0 . 05 ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In conclusion , COX 2 and the inducible isoform of PGE ( 2 ) synthase appear to be constitutively and selectively present in medullary epithelial cells of the human thymus , whereas COX 1 is predominantly present in the thymic cortex , both in the stroma and in developing thymocytes . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin ( IND ) , an inhibitor preferentially acting on COX 1 , as well as nimesulide ( NIM ) and celecoxib ( CECOX ) , i . e . respectively preferential and selective inhibitors of COX 2 , markedly decreased the antinociceptive activity of ACETA in Randall Selitto test . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the current studies , the following intracellular events were found to be also induced by cadmium : ( 1 ) a specific rise in cyclooxygenase 2 ( COX 2 ) gene expression but not COX 1 ; ( 2 ) an increase in the extracellular levels of the proinflammatory prostaglandin E 2 , a product of COX 2 ; and ( 3 ) production of 4 hydroxy 2 nonenal protein adducts , which result from lipid peroxidation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists as COX 1 and COX 2 isoforms . ^^^ COX 1 and COX 2 protein was measured by immunoblotting using specific antibody . ^^^ Untreated HUVEC contained COX 1 protein but not COX 2 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Before eradication , the mRNA expression for gastrin and CCKB R as well as mRNA expression for COX 1 and COX 2 were observed in tumor tissue and infected mucosa , while corpus mucosa expressed only CCKB R and antrum mucosa only gastrin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Role for both spinal cord COX 1 and COX 2 in maintenance of mechanical hypersensitivity following peripheral nerve injury . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , the caput and cauda regions of the epididymis and the vas deferens in this order showed a progressive increase in the expression of COX 1 mRNA and immunoreactivity , whereas COX 2 was dominantly expressed in the vas deferens . ^^^ COX 1 was localized in epithelial cells of the caput , corpus and cauda epididymis and of the vas deferens , and COX 2 was evident in epithelial cells of the distal cauda epididymis and vas deferens . ^^^ These results show that mPGES 1 is expressed coordinately with COX 1 and COX 2 and is involved in PGE ( 2 ) production in male genital organs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Recently , two isoforms of cyclooxygenase ( COX ) have been identified , a constitutive form ( COX 1 ) and a mitogen inducible form ( COX 2 ) . ^^^ RESULTS : Renal cortical prostacyclin ( PGI 2 ) and COX 2 were significantly upregulated 8 and 12 weeks after NX , while COX 1 remained at the basal level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To determine whether the induction of NAG 1 by NSAIDs is influenced by COX expression , we developed COX 1 and COX 2 overexpressing HCT 116 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The enzymes responsible for PG synthesis are cox 1 and cox 2 . ^^^ Cox 1 regulates physiological functions in gut and kidney while cox 2 induces inflammation . ^^^ Selective cox 2 inhibitors have little effect on cox 1 and thus showed better GI tolerability . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The tachyphylaxis induced by BK was unaffected by L NOARG ( nitric oxide synthase inhibitor , 100 microM ) or valeryl salicylate ( a cyclooxygenase 1 ( COX 1 ) inhibitor , 30 microM ) , but was prevented by a low concentration of indomethacin , diclofenac ( non selective COX inhibitors , 3 nM each ) or by NS 398 ( a COX 2 inhibitor , 10 nM ) . ^^^ Furthermore , the tachyphylaxis induced by BK was insensitive to the nitric oxide and COX 1 inhibitors , but was prevented by non selective and selective COX 2 inhibitors , indicating a mediation via COX 2 derived arachidonic acid metabolites . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , increased glomerular volume and increased expression of TGF beta , alpha SMA as well as COX 1 and COX 2 were found in normotensive nephritic rats and in both kidneys of nephritic hypertensive rats . ^^^ In contrast , the clipped kidney is completely protected from this immunological injury despite similar activation of glomerular cells , induction of TGF beta , COX 1 and COX 2 and glomerular hypertrophy . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By immunocytochemistry , COX 1 was observed in CD 34 ( + ) cells and in megakaryocytes at each stage of maturation , whereas COX 2 was induced after 6 days of culture , and remained detectable in mature megakaryocytes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : Cyclo oxygenases 1 and 2 ( COX 1 and COX 2 ) are key enzymes in prostaglandin biosynthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we demonstrate that selective COX 2 inhibitors significantly reduced postsynaptic membrane excitability , back propagating dendritic action potential associated Ca2+ influx , and long term potentiation ( LTP ) induction in hippocampal dentate granule neurons , while a COX 1 inhibitor is ineffective . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , data suggest neither the COX 1 nor the COX 2 enzyme to be of major importance for 5 HT induced ion transport in rat colon in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We utilized wild type , COX 1 ( / ) , and COX 2 ( / ) mice to demonstrate that COX 2 plays an essential role in both endochondral and intramembranous bone formation during skeletal repair . ^^^ The healing of stabilized tibia fractures was significantly delayed in COX 2 ( / ) mice compared with COX 1 ( / ) and wild type controls . ^^^ Similarly , intramembranous bone formation on the calvaria was reduced 60 % in COX 2 ( / ) mice following in vivo injection of FGF 1 compared with either COX 1 ( / ) or wild type mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibitory activities were assessed at pH 7 for alkamides isolated from E . purpurea roots to compare inhibitory activities between the two cyclooxygenase isozymes . ^^^ At 100 microg / ml , several E . purpurea alkamides inhibited COX 1 and COX 2 enzymes in the range of 36 60 % and 15 46 % , respectively , as compared to controls . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : To compare the effects of nabumetone and meloxicam , two cyclo oxygenase 2 ( COX 2 ) preferential nonsteroidal anti inflammatory drugs ( NSAIDs ) , on platelet COX 1 activity and platelet function . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Phospholipase A ( 2 ) ( PLA ( 2 ) ) and cyclooxygenase ( COX ) are two key enzymes in PG synthesis ; the latter has two forms , COX 1 and COX 2 . mRNA was extracted from single preimplantation embryos and examined for PLA ( 2 ) , COX 1 , and COX 2 gene expression by RT PCR to investigate whether PLA ( 2 ) and COX genes are expressed in human preimplantation conceptuses from zygote to blastocyst stage and to compare COX 1 and COX 2 gene expression within the same stage of embryonic development . ^^^ Expression of PLA ( 2 ) , COX 1 , and COX 2 was detected in 48 , 37 , and 45 % , respectively , of total embryos examined . ^^^ COX 1 was expressed in approximately 66 % of early human preimplantation embryos from zygote to two cell stage , whereas COX 2 was expressed in about 58 % of later stage embryos from eight cell to blastocyst stage ( P < 0 . 05 ) . ^^^ In conclusion , PLA ( 2 ) , COX 1 , and COX 2 are expressed during early human embryonic development and may contribute to the production of PGs such as PGE ( 2 ) in human embryogenesis . ^^^ COX 1 and COX 2 are differentially expressed , with COX 2 being primarily expressed by trophectoderm in late stage human preimplantation embryos , which may promote embryonic differentiation and implantation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Increased prostaglandins ( PGs ) are associated with many inflammatory pathophysiological conditions ; and are synthesized from arachidonic acid by either of 2 enzymes , cyclooxygenase 1 ( COX 1 ) or 2 ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIM : This study was aimed to evaluate the effect of drugs inhibiting both cyclooxygenase ( COX ) isoforms COX 1 and COX 2 on vasoconstrictor responses to noradrenaline in the rabbit renal artery and to compare these responses with femoral artery as a systemic vessel . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostanoids are required , as indomethacin blocked the effect of TGF beta 1 , and Cox 1 , but not Cox 2 , is involved . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two isoforms of cyclooxygenase ( COX 1 and COX 2 ) are reviewed along with the newer NSAID which are more effective and less toxic due to more specific COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
For Western blotting , expression of eNOS and COX 1 was decreased in A compared with Y arterioles , whereas expressions of COX 2 , Cu / Zn SOD , Mn SOD , xanthine oxidase , and the NAD ( P ) H oxidase subunits p 47 ( phox ) , p 67 ( phox ) , Mox 1 , and p 22 ( phox ) did not differ . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , selective inhibition of COX 2 , but not COX 1 , blocked PGI 2 production under low cholesterol conditions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , COX 2 , and not COX 1 , is the isoform most frequently reported to have a key role in tumor development . ^^^ Here we report that homozygous deficiency of either COX 1 or COX 2 reduces skin tumorigenesis by 75 % in a multistage mouse skin model . ^^^ The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10 , two keratins that indicate the commitment of keratinocytes to differentiate , were expressed 8 13 fold and 10 20 fold more frequently in epidermal basal cells of the COX 1 deficient and COX 2 deficient mice , respectively , than in wild type mice . ^^^ Because keratin 5 , a keratin associated with basal cells , was detected differently in papillomas of COX 1 deficient as compared with COX 2 deficient mice , it appears that the isoforms do not have identical roles in papilloma development . ^^^ Thus , both COX 1 and COX 2 have roles in keratinocyte differentiation , and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we determined the effect of different prodelphinidins , the major compounds isolated from Ribes nigrum leaves , on the proteoglycans ( PGs ) , type 2 collagen ( coll . 2 ) and prostaglandin E ( 2 ) ( PGE ( 2 ) ) production by differentiated human chondrocytes cultivated in long term ( 12 days ) and in clusters as well as their inhibition potential on COX 1 and COX 2 in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : The existence of two isoforms of cyclo oxygenase ( COX ) , COX 1 and COX 2 , is now well established . ^^^ Because inhibition of COX 1 by nonsteroidal anti inflammatory drugs ( NSAIDs ) is linked to gastrointestinal ( GI ) damage , agents with a better COX 2 / COX 1 inhibition ratio may have less GI toxicity . ^^^ The use of `` COX 1 preferential ' ' inhibitors versus `` COX 2 preferential ' ' inhibitors was associated with a RR of 5 . 3 ( 95 % CI , 2 . 78 10 . 04 ) , and between NSAIDs with `` COX 1 COX 2 mixed ' ' inhibition RR was 2 . 2 ( 95 % CI , 1 . 13 4 . 28 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The enzymatic activities of COX 1 and 2 are inhibited by resveratrol in cell free models , and COX 2 mRNA and TPA induced activation of protein kinase C and AP 1 mediated gene expression are suppressed by resveratrol in mammary epithelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been identified : COX 1 , the constitutive isoform ; and COX 2 . the inducible form of the enzyme . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the fully embryonic cortical zone immunohistochemical expression of COX 1 is seen in all cells of the CD ampulla , while COX 2 is lacking within the nephron inducer . ^^^ As revealed by western blot experiments generated embryonic CD epithelia in perfusion culture demonstrate high COX 1 presence at the begin of culture , while COX 2 is found to a minor degree . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 mRNA and protein are not expressed on any day of the estrous cycle , whereas COX 2 mRNA and protein and PGES mRNA are differentially expressed and regulated in bovine endometrium during the estrous cycle . ^^^ COX 2 , rather than COX 1 , is the primary isoenzyme involved in the endometrial production of prostaglandins , and the COX 2 and PGES pathway is responsible for the endometrial production of PGE ( 2 ) in the bovine endometrium during the estrous cycle . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Sequences were obtained for the cox 1 , cox 2 , 16S , 28S genes , the regions between the cox 2 and atp 8 genes , and between the nad 3 and nad 5 genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 and articular joint disease : a role for chondroprotective agents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The clinical relevance of COX 1 compared with COX 2 inhibition is discussed to provide a framework upon which clinicians can better appreciate current and future therapeutic applications of coxibs . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The gastrointestinal toxicity of nonselective NSAIDs and aspirin derives from the inhibition of the cyclooxygenase ( COX ) enzyme , COX 1 , which synthesizes gastroprotective prostaglandins , while the anti inflammatory and pain relieving effects are largely derived from inhibition of COX 2 derived prostaglandins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cap markedly suppressed the expression of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Different types of tumor promoters elevate COX 2 expression in keratinocytes , with little change in COX 1 , suggesting that there are multiple signaling pathways by which COX 2 expression can be regulated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX enzymatic system includes two isoenzymes , COX 1 and COX 2 , that convert arachidonic acid to prostaglandins . ^^^ The recent development of selective COX 2 inhibitors resulted in better clinical tolerance than that associated with NSAIDs in general , with the absence of gastrointestinal side effects known to occur after the inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 mRNAs in atherosclerotic plaques . ^^^ There are two isoforms : COX 1 and COX 2 . ^^^ COX 1 is relatively stable while COX 2 is induced in inflammatory states . ^^^ Total RNA was extracted and relative levels of COX 1 and COX 2 determined by the technique of RT PCR . ^^^ There was no relationship between sex , age , postmortem delay or cause of death and COX 2 or COX 1 levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a new non steroidal anti inflammatory drug ( NSAID ) , which has a higher activity cyclooxygenase 2 ( COX 2 ) than against cyclooxygenase 1 ( COX 1 ) , with potentially high anti inflammatory and analgesic action . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit the function of cyclooxygenases , COX 1 and COX 2 , which catalyze the first step in the synthesis of inflammatory mediators ( PGE 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present studies were undertaken to elucidate the roles of COX 1 and COX 2 in regulating blood pressure and renal function . ^^^ Ang 2 infusion also reduced medullary blood flow in COX 2 deficient but not in control or COX 1 deficient animals , suggesting synthesis of COX 2 dependent vasodilators in the renal medulla . ^^^ Thus , COX 1 and COX 2 exert opposite effects on systemic blood pressure and renal function . ^^^ These results suggest that , rather than having similar cardiovascular effects , the activities of COX 1 and COX 2 are functionally antagonistic . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study was designed to investigate whether administration of indomethacin ( IMC ) , a non selective cyclooxygenase ( COX 1 and COX 2 ) inhibitor , and Rofecoxib , a highly selective COX 2 inhibitor , affect the regulation of regional cerebral blood flow response evoked by somatosensory activation ( evoked rCBF ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we first tested whether this phenomenon also occurs in bone tissue in vivo and found that a single anabolic dose of PGE ( 2 ) ( 5 mg / kg ) induced ( between 30 and 120 min ) in rat tibiae , an increase in the mRNA level of COX 2 ( 2 . 5 to 9 fold ) but not that of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Skin biopsies were taken at 6 h to determine numbers of mast cells , eosinophils , basophils , Langerhans ' cells , and monocytes / macrophages , and the expression of COX 1 , COX 2 , 5 LO and FLAP . ^^^ Immunocytochemical examination of biopsies taken at 8 h showed increased numbers of eosinophils and basophils and in COX 2 , 5 LO and FLAP , but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Herein , we demonstrate that the expression , induction , and subcellular localization of COX 1 and COX 2 and the downstream PG biosynthesis are markedly different between these subsets . ^^^ Specifically , Thy 1 ( + ) fibroblasts highly express COX 1 , which is responsible for high level PGE ( 2 ) production , a feature usually attributed to the COX 2 isoenzyme . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It was also antagonized by the non specific cyclooxygenase ( COX ) inhibitor , indomethacin , and by the selective COX 2 inhibitor , NS 398 , but not by the specific COX 1 inhibitor , valeryl salicylate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , Sprague Dawley rats were subjected to different salt diets [ 0 . 02 , 0 . 6 , and 8 % NaCl ( wt / wt ) ] and treated with the selective COX 2 inhibitor rofecoxib ( 10 mg 10 kg body wt ( 1 ) 10 day ( 1 ) ) or with ketorolac at a dose selective for COX 1 inhibition ( 2 mg 10 kg body wt ( 1 ) 10 day ( 1 ) ) for 3 , 7 , 14 , and 21 days . ^^^ Prolonged treatment with rofecoxib but not with ketorolac caused an upregulation of COX 2 expression while COX 1 mRNA abundance remained unchanged . ^^^ These findings suggest that COX 1 derived , but not COX 2 derived , prostanoids are of relevance for the regulation of the renin system by salt intake . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present studies an involvement of adrenergic system and prostaglandins synthesized by constitutive cyclooxygenase ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) in the nicotine induced HPA response in rats was investigated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prolonged expression of COX 2 protein was observed in PDT treated mouse sarcoma and carcinoma cell lines , whereas COX 1 was not inducible by PDT . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At the opposite , treatment of mice with either a COX 1 + COX 2 inhibitor ( aspirin , 1 mg / day / mouse ) or a specific COX 2 inhibitor ( celecoxib , 0 . 13 mg / day / mouse ) for 2 weeks after injection of tumor cells , significantly reduced the size and growth rate of tumors compared to control mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the rate limiting enzyme for the production of prostaglandins ( PG ) from arachidonic acid , exists in at least two isoforms , COX 1 and COX 2 . ^^^ COX 1 is constitutively expressed in most tissues and plays various physiological roles , whereas increased COX 2 expression is known to occur in several types of epithelial neoplasms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compounds 6 11 were tested in vitro for their inhibitory activity towards COX 1 and COX 2 by measuring prostaglandin E 2 ( PGE 2 ) production in U 937 cell lines and activated J774 . 2 macrophages , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The constitutively expressed cyclooxygenase 1 ( COX 1 ) appears to regulate many normal physiologic functions in several cell types , whereas the inducible cyclooxygenase 2 ( COX 2 ) enzyme mediates the inflammatory response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An up regulation of COX 2 , c fos , and c jun , but not COX 1 , was observed around the lesion as well as in the neocortex 4 hr after the injection . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In an attempt to define the roles of prostaglandin H synthase 1 ( PGHS 1 , cyclooxygenase 1 , COX 1 ) and prostaglandin H synthase 2 ( PGHS 2 , cyclooxygenase 2 , COX 2 ) in wound healing , we investigated the healing of incisional dermal wounds in wild type , PGHS 1 null , and PGHS 2 null mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At 250 pg ml ( 1 ) , compounds 1 4 , 6 and 7 displayed prostaglandin H endoperoxide synthase 1 ( COX 1 ) and prostaglandin H endoperoxide synthase 2 ( COX 2 ) inhibitory activities at pH 7 . ^^^ The acetylated product ( 5 ) of compound 4 also inhibited COX 1 and COX 2 enzymes when tested at 250 microg ml ( 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we investigated the effect of a specific PPARgamma ligand , ciglitazone , on the course of buccal mucosal ulcer healing by analyzing mucosal activity of inducible nitric oxide synthase ( NOS 2 ) and the expression cyclooxygenases ( COX 1 and COX 2 ) responsible for prostaglandin ( PG ) generation . ^^^ Administration of ciglitazone led to a significant dose dependent acceleration in the mucosal reduction of PGE 2 generation and NOS 2 activity , and produced a marked decline in COX 2 and NOS 2 protein expression , but the rate of ulcer healing and the expression of COX 1 protein remained unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synthesis of cinnamyl or coumarinyl substituted ethanolamide derivatives of indomethacin produced fluorescent probes of inhibitor interaction with COX 2 and COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Similarly , Indomethacin ( Indo ) damage ( COX 1 COX 2 ) , with 25 mgs / kg . ^^^ On the other hand , De and Ke at inhibitory selective COX 1 dose ( 3 mg / kg ) plus Celecoxib , selective COX 2 inhibitor , yielding no gastrointestinal damage , with decreased LI and without neutrophilia , the same as Ke ( n . s . ) . ^^^ On the other hand , COX 1 De dose plus Celecoxib produced evident gastrointestinal lesions , increased LI and neutrophilia , the same as Indo , pointing out that the gastrointestinal damage is due to COX 1 and COX 2 inhibition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective inhibition of COX 2 by indomethacin amid or indomethacin n heptyl ester did not inhibit [ ( 14 ) C ] PAH uptake , whereas selective inhibition of COX 1 dose dependently inhibited [ ( 14 ) C ] PAH uptake . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Structure activity relationship of indomethacin analogues for MRP 1 , COX 1 and COX 2 inhibition . identification of novel chemotherapeutic drug resistance modulators . ^^^ Two of the MRP 1 inhibitory analogues were found to have no COX 1 inhibitory activity and low COX 2 inhibitory activity , suggesting potentially reduced clinical toxicity . ^^^ One MRP 1 inhibitory indomethacin analogue was also found to have low COX 1 inhibitory activity , but significant COX 2 inhibitory activity , making this analogue again interesting in terms of low potential toxicity , but with the possibility of direct inhibitory effects on tumour growth . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Aspirin , a nonselective COX 1 ( cyclo oxygenase ) and COX 2 inhibitor may result in gastric toxicity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , primary rat hepatocyte cultures , exhibiting time dependent mdr1b overexpression , demonstrated basal COX 2 and COX 1 mRNA expression and liberation of prostaglandin E ( 2 ) ( PGE ( 2 ) ) , indicative of an active COX dependent arachidonic acid metabolism . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of COX , namely COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed unchanged sciatic nerve COX 1 protein but increased COX 2 protein abundance in STZ D versus ND rats . ^^^ These results imply 1 ) a tonic role of the COX 1 pathway in the regulation of nerve osmolytes and Na , K ATPase activity and the maintenance of NBF in ND animals and 2 ) activation of the COX 2 pathway as an important mediator of NBF and MNCV deficits in EDN . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIM : To develop a whole cell assay based on murine peritoneal macrophages and evaluate the inhibitory effect of candidate compounds on cyclooxygenase 1 ( COX 1 ) and COX 2 . ^^^ RESULTS : Rofecoxib selectively inhibited LPS induced , COX 2 derived PGE 2 synthesis with an IC 50 value of ( 4 . 7+ / 0 . 5 ) nmol / L compared with maximum inhibitory ratio of 17 . 3 % for the inhibition of calcimycin induced , COX 1 derived 6 keto PGF1alpha synthesis . ^^^ Indomethacin exhibited dual inhibitory effects on COX 1 and COX 2 with IC 50 of ( 4 . 7+ / 1 . 1 ) nmol / L and ( 7 . 1+ / 1 . 2 ) nmol / L , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is generally believed that COX 1 is constitutively expressed , whereas COX 2 is primarily inducible during inflammation . ^^^ CONCLUSIONS : The suppression of products of COX 2 coincident with pain suppression and the absence of COX 1 inhibition suggest that celecoxib is a relatively selective COX 2 inhibitor in vivo . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The main target of most NSAIDs is the enzyme cyclo oxygenase ( COX ) , which occurs in 2 isoforms , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we characterized COX mediated arachidonic acid metabolism in NMBA induced rat esophageal tumorigenesis by measuring COX 1 and COX 2 expression and prostaglandin E ( 2 ) production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , which acts in the synthesis of PG from arachidonic acid , has been recently revealed to have two subtypes , a constitutive type ( COX 1 ) and an inducible one ( COX 2 ) . ^^^ The expression of both COX 1 and COX 2 genes was enhanced after colchicine injection in the early stage before the start of bone formation . ^^^ Moreover , the present study suggests that COX 2 and COX 1 would both be involved in the early stage of osteogenesis , and COX 2 is likely to be more associated with the maturation of osteoblasts in the later stage . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAIDs ) inhibit cyclooxygenase 1 ( COX 1 ) , thereby inhibiting platelet function via blockade of thromboxane A 2 ( TxA 2 ) formation , and COX 2 , the enzyme that mediates inflammatory responses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , the lung fibrotic responses were investigated in COX 1 or COX 2 deficient ( / ) mice following vanadium pentoxide ( 5 ( 2 ) O ( 5 ) ) exposure . ^^^ COX 2 ( / ) , but not COX 1 ( / ) or wild type mice , exhibited severe inflammatory responses by 3 days following 5 ( 2 ) O ( 5 ) exposure and developed pulmonary fibrosis 2 weeks post 5 ( 2 ) O ( 5 ) exposure . ^^^ Western blot analysis and immunohistochemistry showed that COX 1 protein was present in type 2 epithelial cells , bronchial epithelial cells , and airway smooth muscle cells of saline or 5 ( 2 ) O ( 5 ) exposed wild type and COX 2 ( / ) mice . ^^^ COX 2 protein was present in Clara cells of wild type and COX 1 ( / ) terminal bronchioles and was strongly induced 24 hours after 5 ( 2 ) O ( 5 ) exposure . ^^^ Prostaglandin ( PG ) E ( 2 ) levels in the bronchoalveolar lavage ( BAL ) fluid from wild type and COX 1 ( / ) mice were significantly up regulated by 5 ( 2 ) O ( 5 ) exposure within 24 hours , whereas PGE ( 2 ) was not up regulated in COX 2 ( / ) BAL fluid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
DEP extract and the PAHs inhibit the activity of purified COX 2 enzyme in vitro but do not inhibit COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Observations were made with and without inhibition of constitutive ( endothelial constitutive NOS ( ecNOS ) and COX 1 ) and inducible isoforms ( iNOS and COX 2 ) of NOS and COX . ^^^ Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX related pathway was judged from perfusate concentrations of 6 ketoprostaglandin F1alpha . ecNOS and COX 1 , but not iNOS and COX 2 , were upregulated in hyperoxia injured lungs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to compare the effects of two nonsteroidal anti inflammatory drugs ( NSAID ) , members of the same family with a different cyclooxygenase ( COX ) inhibition selectivity , meloxicam , preferent COX 2 inhibitor , and piroxicam , preferent COX 1 inhibitor , on oxygen radical generation in rat gastric mucosa . ^^^ These results suggest that under our experimental conditions , meloxicam , preferential COX 2 inhibitor causes rates of gastric lesion in rats comparable to those seen with the traditional NSAID piroxicam , preferential COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of constitutive and inducible cyclooxygenase ( COX 1 and COX 2 , respectively ) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed ( MVB ) from the portal vein ligated rat ( PVL ) as a model of portal hypertension . ^^^ Functional experiments were carried out in MVB from PVL and sham operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX 1 ( SC 560 ) or COX 2 ( NS 398 ) . ^^^ Western blots of COX 1 and COX 2 proteins were evaluated in aorta and MVB , and PGI ( 2 ) production by enzyme immunoassay of 6 keto PGF ( 1alpha ) was evaluated in the aorta . ^^^ Upregulation of COX 1 and COX 2 expressions was detected in aorta and MVB from PVL portal hypertensive rats , and increased production of 6 keto PGF ( 1alpha ) was observed in aorta from portal hypertensive rats . ^^^ These results suggest that generation of endothelial vasodilator prostanoids , from COX 1 and COX 2 isoforms , accounts for the increased mesenteric blood flow in portal hypertension . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MPTP ( 20 mg / kg , subcutaneously ) was injected daily into COX 1 and COX 2 deficient mice and wild type ( WT ) controls for five consecutive days . ^^^ Furthermore , electrochemical analysis revealed a more than 70 % decrease in the levels of dopamine and its metabolites ( 3 , 4 dihydroxyphenylacetic acid and homovanillic acid ) in the striatum of the WT control COX 1 ( / ) and COX 2 ( / ) mutant mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We quantitated mRNA levels for enzymes involved in the prostaglandin biosynthetic pathways and found that both COX 2 and PGE synthase ( PGEs ) mRNA levels were increased in the brain ; no changes were found for expression of COX 1 or PGD synthase mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Earlier studies with COX knockout ( COXko ) mice suggested that COX 2 was more important for hypophagia than COX 1 . ^^^ These results suggest that shortly after IL 1beta administration , COX 1 is the major enzyme involved in the reduction of milk intake , whereas at later times COX 2 is more important , paralleling its induction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
With the use of long primers ( 43 bp ) derived from regions of homology between zebrafish and rainbow trout COX 2 genes , a 600 bp product was amplified from SRG and was found to be almost equally homologous to mammalian COX 1 and COX 2 ( 65 % ) . ^^^ The longest open reading frame encodes a 593 amino acid protein that has 68 and 64 % homology to mammalian COX 1 and COX 2 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study provides definitive evidence that metabolites of COX 2 rather than COX 1 mediate ACEI induced renin increases . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , intrarenal COX isoforms may play differential roles , with COX 1 participating in modulation of renal hemodynamics , and COX 2 contributing to sodium excretion and Ang 2 formation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX is found in the 2 isoforms COX 1 ( a constitutive form ) and COX 2 ( an inducible form ) . ^^^ Due to the side effects associated with COX 1 inhibition there is great interest in selective COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , genetic disruption of COX 1 , the other isoform , was shown to decrease the number of intestinal polyps and prostaglandin E ( 2 ) levels in intestinal mucosa , like the case with COX 2 gene disruption , in Min mice . ^^^ The data indicate that both COX 1 and COX 2 can contribute to intestinal tumorigenesis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Semi quantitative RT PCR and ELISA analysis demonstrated that following NMBA treatment , the expression of COX 1 mRNA was strongly present in tumor tissues , while weakly present in non tissues ; the expression of COX 2 mRNA was induced in both tumor and non tumor tissues . ^^^ The higher expression of COX 1 , the up regulated COX 2 expression and the increased levels of PGE ( 2 ) synthesis were all significantly decreased by administering resveratrol . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Classical cyclooxygenase ( COX ) inhibitors , such as indomethacin , which inhibit both COX 1 and COX 2 , are effective for delaying premature labor , but their use is limited by serious complications to the fetus and neonate , including adverse effects on the ductus arteriosus ( DA ) . ^^^ Therefore , COX 1 selective inhibitors may provide effective treatment to delay preterm labor with fewer adverse effects on fetal or neonatal health than nonselective or COX 2 selective inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSION : The temporal profile of PGE ( 2 ) and TxB ( 2 ) in the immediate postoperative period is consistent with constitutive COX 1 initially , followed by an increase in PGE ( 2 ) resulting from expression of COX 2 . ^^^ The temporal association between NSAID analgesia and decreased prostanoids at the site of injury is consistent with a dual COX 1 / COX 2 peripheral site of action . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The similarity between response to indomethacin and nm 23 transfection led us to 1 ) expand our ( 1 ) H NMR spectroscopy study of indomethacin treatment by determining the response at two doses for two nonmalignant and three malignant HMECs , 2 ) investigate COX 1 and COX 2 levels in HMECs and their relationship with choline phosholipid metabolites , and 3 ) determine changes in Nm 23 expression following treatment with indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostanoids are arachidonic acid ( AA ) metabolites derived from the cyclooxygenase ( COX 1 and COX 2 isozymes ) pathway and are involved in signal transduction pathways activated by distinct ILs . ^^^ Although COX 1 is the constitutive isoform of COX , IL 1beta is a potent inducer of COX 2 expression in distinct cell types . ^^^ COX function was assessed using COX activity inhibitors : indomethacin ( INDO ; COX 1 and COX 2 inhibitor ) and NS 398 ( COX 2 selective inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 contributions to basal and IL 1 beta stimulated prostanoid synthesis in human neonatal cerebral microvascular endothelial cells . ^^^ Increased COX 2 linked activity in response to IL 1 beta was observed in hCMVEC from both cerebrum and cerebellum ( 5 to 20 fold ) , while under the same conditions elevated COX 1 linked activity was detected only in hCMVEC from cerebellum ( 5 to 10 fold ) . ^^^ Altogether , these data indicate that both COX 1 and COX 2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL 1 beta . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 positive cell counts increased from 0 to 2 . 6 cells / mm ( 2 ) ( P = . 009 ) , with no change in COX 1 levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
About ten years ago , two COX isoforms were demonstrated : COX 1 whose products are involved in regulating physiological functions and COX 2 which is expressed by a number of inflammatory stimuli . ^^^ The discovery of molecular differences between COX 1 and COX 2 allowed the development of pharmacological agents selectively inhibiting COX 1 or COX 2 . ^^^ However , COX 1 products are involved in inflammatory reactions , whereas COX 2 products play a physiological role in many tissues and organs , including the kidney . ^^^ CONCLUSIONS : The case we report seems to confirm that , in patients at risk , the renal adverse effects of non selective NSAIDs and of COX 2 Inhibitors could be the same due to the similar physiological role of COX 1 and COX 2 dependent prostaglandins . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Quantitative and real time PCR analysis showed enhanced COX 2 mRNA expression in thrombin or TRAP stimulated HUVEC whereas COX 1 expression was unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two COX isoforms have been identified , COX 1 and COX 2 that form PGH 2 , a common precursor for the biosynthesis of thromboxane A 2 ( TxA 2 ) , prostacyclin ( PGI 2 ) and PGs ( PGD 2 , PGE 2 , PGF2alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These differences from the horse might be the result of : ( a ) the presence in equine biological fluids of higher concentrations than in calves of the active PBZ metabolite , OPBZ ; ( b ) a greater degree of binding of PBZ to plasma protein in calves ; ( c ) species differences in the sensitivity to PBZ of the cyclo oxygenase ( COX ) isoenzymes , COX 1 and COX 2 or ; ( d ) a combination of these factors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is crucial in inflammation ; COX 1 is constitutional , and COX 2 is inducible . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Melatonin given simultaneously with the non selective COX 1 and COX 2 inhibitor indomethacin ( 5 mg kg ( 1 ) , i . p . ) 30 min prior to carrageenan , enhanced the anti inflammatory effect of the latter in the carrageenan induced paw oedema model by 23 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All isolates were evaluated for their potential to induce human promyelocytic leukemia ( HL 60 ) cell differentiation , and to inhibit cyclooxygenase 1 ( COX 1 ) , 2 ( COX 2 ) , and 7 , 12 dimethylbenz [ a ] anthracene ( DMBA ) induced lesions in a mouse mammary organ culture model . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All of the tested THPs exhibited COX 1 and COX 2 nonselective inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The NSAIDs used in our experimental model are selective or non selective COX 1 inhibitors as well as one non selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS AND RESULTS : Exposure of human umbilical vein endothelial cells to laminar shear stress in the physiological range ( 1 to 30 dyne / cm2 ) upregulated the expression of COX 2 but not COX 1 , a constitutive isozyme of COX . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists as two unique isoforms ( that is , COX 1 and COX 2 ) which are poorly understood with regard to their roles in renal function . ^^^ Drugs that selectively inhibit COX 2 provide useful pharmacological tools for discerning the effects associated with the inhibition of the individual isoforms , and may help clarify the renal roles of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both drugs markedly lowered COX 2 expression while COX 1 expression remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the influence of AD plaque associated factors on COX 1 and COX 2 expression and activity in adult human microglial cells in vitro . ^^^ COX isotype selective inhibitors were used to discern relative contributions of COX 1 and COX 2 activities to microglial PGE ( 2 ) secretion . ^^^ COX 2 and in part COX 1 selective inhibitors inhibited LPS induced PGE ( 2 ) secretion , whereas the AA induced PGE ( 2 ) secretion was reduced by COX 1 selective inhibitors only . ^^^ Apparently , adult human microglia in vitro ( 1 ) constitutively express COX 1 , and ( 2 ) do not express COX 2 upon exposure to either Abeta or plaque associated cytokines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression was determined in 4 liver tumor cell lines ( Hep 3B , HuH 7 , Hep G 2 , Sk hep 1 ) by Northern hybridization and Western immunoblot . ^^^ COX 1 and COX 2 expression was demonstrable in all tested liver tumor cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROBLEM : Human endometrial glands contain the highest levels of cyclooxygenase ( COX ) , although whether it is COX 1 and / or COX 2 has not been previously determined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA and protein were assessed in the human ureter , in normal human bladder muscle and urothelium , and in urine particulates from patients with urinary tract infections , bladder cancer and bladder cancer with BCG treatment . ^^^ RESULTS : COX 1 protein , and mRNA and COX 2 mRNA were expressed in the ureter , and bladder muscle and urothelium . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study was designed ( 1 ) to determine the plasma levels of progastrin and amidated gastrin in 50 CRC patients before and 3 6 months after removal of the tumor , ( 2 ) to determine the tumor concentrations of these gastrin peptides and the level of expression for gastrin mRNA and gastrin / CCK ( B ) receptor mRNA , ( 3 ) to examine the expression of cyclooxygenase COX 1 and COX 2 mRNA in CRC tissue , and ( 4 ) to compare the prevalence of Hp and its cytotoxic protein , CagA , and cytokines ( TNFalpha , IL 1beta , and IL 8 ) in CRCs , before and after removal of tumor . ^^^ Both gastrin and CCK ( B ) R mRNA were detected in the cancer tissue and resection margin by RT PCR , and similarly , COX 1 and COX 2 mRNA were expressed in these tissues of most CRCs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , SC 560 ( a selective COX 1 inhibitor ) and rofecoxib ( a selective COX 2 inhibitor ) were given intraduodenally 1 hr before exposure to 10 mM HCl , while N ( G ) nitro L arginine methyl ester ( L NAME : a nonselective NOS inhibitor ) and aminoguanidine ( a relatively selective inhibitor of iNOS ) were given subcutaneously 3 hr before the acidification . ^^^ Neither COX 2 nor iNOS mRNAs were observed in the mucosa before and 1 hr after acidification , while the gene expression of COX 1 and nNOS was constitutively detected in the mucosa and appeared to be slightly up regulated after the acid stimulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By using immunohistochemistry , we have compared the cellular expression and localization of COX 1 and COX 2 in the normal mouse , rat , and human retina . ^^^ These results suggest that prostaglandins , synthesized by COX 1 or COX 2 , may contribute to normal physiological and homeostatic functions in the retina . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Flavonoids and stilbenoids with COX 1 and COX 2 inhibitory activity from Dracaena loureiri . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile injured colon by preventing production of reparative prostaglandins , whereas the selective COX 2 inhibitor , etodolac would not inhibit repair as a result of continued COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Acute pancreatitis was induced in Swiss Webster mice or mice deficient in the COX 2 ( Ptgs 2 ) or the COX 1 ( Ptgs 1 ) genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The findings of the present study further suggested that COX 1 derived rather than COX 2 derived PGs might play a potential role in haloperidol induced catalepsy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The Lamarckian genetic algorithm of AutoDock 3 . 0 has been employed to dock 40 1 , 5 diarylpyrazole class compounds into the active sites of cyclooxygenase 2 ( COX 2 ) and cyclooxygenase 1 ( COX 1 ) . ^^^ The data of geometrical parameters and RMSD values compared with the known inhibitor , SC 558 ( 43 ) , show that these inhibitors interact respectively with COX 2 and COX 1 in a very similar way . ^^^ The r ( 2 ) values of 0 . 648 for COX 2 and 0 . 752 for COX 1 indicate that the calculated binding free energies correlate well with the inhibitory activities . ^^^ The structural and energetic differences in inhibitory potencies of 1 , 5 diarylpyrazoles were reasonably explored , and the COX 2 / COX 1 selectivity was demonstrated by the three dimensional ( 3D ) interaction models of inhibitors complexing with these two enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Docking studies were also carried out wherein these analogues were docked into the active sites of both COX 1 and COX 2 to analyze the receptor ligand interactions that confer selectivity for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study sought to determine 1 ) the functional selectivity of carbachol for cholinergic muscarinic and / or nicotinic receptors involved in the stimulation of HPA axis ; 2 ) the involvement of prostaglandins ( PGs ) generated by constitutive and inducible cyclooxygenase ( COX 1 and COX 2 ) in the carbachol induced ACTH and corticosterone secretion in non stressed rats and animals exposed to social crowding stress for 7 days ( 24 per a cage for 6 ) . ^^^ These results indicate that in the carbachol induced HPA axis activation PGs generated by COX 1 are considerably and to a much greater extent involved than PGs generated by COX 2 . ^^^ Social stress markedly diminishes the mediation of PGs generated by COX 1 but PGs synthesized by COX 2 do not substantially participate in the carbachol induced HPA response . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND AND OBJECTIVES : After peripheral inflammatory stimuli , spinal cord cyclooyxgenase 2 ( COX 2 ) mRNA and protein levels increase , whereas COX 1 is unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The PAR 1 induced chloride secretory response was significantly attenuated by inhibitors of the EGF receptor tyrosine kinase , Src kinase , MEK1 / 2 , as well as by inhibitors of cytosolic phospholipase ( cPL ) A 2 , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Phase 3 was accompanied by the induction of cytosolic ( c ) PLA ( 2 ) alpha in the hypothalamus , further upregulation of sPLA ( 2 ) IIA and mPGES in the hypothalamus and liver , and a decrease in the expression of COX 1 and COX 2 in all tissues studied . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The beginning of the nineties gave the evidences , that two cyclooxygenase isoforms existed : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , PGE ( 2 ) synthesis was significantly reduced by COX 1 selective inhibition , yet to a lesser extent by COX 2 selective inhibition . ^^^ Our findings suggest that PMA stimulated PGE ( 2 ) synthesis in mouse podocytes requires both basal COX 1 activity and induced COX 2 expression , and that PGE ( 2 ) reduces PMA stimulated AA release in a cAMP / PKA dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases ( COX 1 and COX 2 ) are the key enzymes involved in PG synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western immunoblotting revealed upregulation of PGI ( 2 ) synthase protein 24 h after BW administration without changes in COX 1 and COX 2 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Abundances of both COX 1 and prostacyclin synthase were reduced , whereas abundances of both COX 2 and thromboxane synthase were unaltered in pulmonary arteries from hypoxic piglets . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Despite the fact that SCLC cell lines expressed little or no cytosolic phospholipase A ( 2 ) , COX 1 , or COX 2 , sulindac sulfide and PPARgamma agonists also inhibited the transformed growth of these lung cancer cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We here investigated the potential inhibitory activity of tryptanthrin and ZE 550 on COX 2 , COX 1 in cellular and cell free systems . ^^^ A certain degree of selectivity towards COX 2 was observed when COX 1 dependent formation of thromboxane B ( 2 ) ( TxB ( 2 ) ) in HEL cells and COX 2 dependent formation of 6 ketoprostaglandin F ( 1alpha ) ( 6 keto PGF ( 1alpha ) ) in Mono Mac 6 and RAW 264 . 7 cells were compared . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
They included the COX 1 inhibitor indomethacin ; the COX 2 inhibitor NS 398 ; the mixed COX 1 / COX 2 inhibitor ibuprofen ; the nitric oxide ( NO ) derivatives of indomethacin , ibuprofen and flurbiprofen ; the 5 LOX inhibitor REV 5901 ; and the 5 LOX activating protein ( FLAP ) inhibitor MK 886 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , the activities of isolated COX 1 and COX 2 were inhibited by taiwanin C ( IC ( 50 ) =1 . 06 and 9 . 31 microM , respectively ) , reflecting the inhibition of both COX 1 and COX 2 dependent PGE ( 2 ) production in the cell culture system . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this screening the N nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0 . 1 10 micromol / L against both COX 1 and COX 2 , while the S nitrooxyacylcysteine derivative had only weak activity against COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By means of its ability to inhibit leukocyte lipid body formation , NS 398 may exert actions independent of its COX 2 inhibition and more broadly contribute to the suppression of formation of COX 1 and lipoxygenase derived eicosanoids . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effect of an ethanolic extract of propolis , with and without CAPE , and some of its components on cyclooxygenase ( COX 1 and COX 2 ) activity in J 774 macrophages has been investigated . ^^^ COX 1 and COX 2 activity , measaured as prostaglandin E 2 ( PGE 2 ) production , were concentration dependently inhibited by propolis ( 3 10 10 ( 3 ) 3 10 10 ( 2 ) microgml ( 1 ) ) with an IC 50 of 2 . 7 microgml ( 1 ) and 4 . 8 10 10 ( 2 ) microgml ( 1 ) , respectively . ^^^ In fact the IC 50 of CAPE for COX 1 and COX 2 were 4 . 4 10 10 ( 1 ) microgml ( 1 ) ( 1 . 5 10 10 ( 6 ) M ) and 2 10 10 ( 3 ) microgml ( 1 ) ( 6 . 3 10 10 ( 9 ) M ) , respectively . ^^^ The IC 50 of galangin were 3 . 7 microgml ( 1 ) ( 15 10 10 ( 6 ) M ) and 3 10 10 ( 2 ) microgml ( 1 ) ( 120 10 10 ( 9 ) M ) , for COX 1 and COX 2 respectively . ^^^ To better investigate the role of CAPE , we tested the action of the ethanolic extract of propolis deprived of CAPE , which resulted about ten times less potent than the extract with CAPE in the inhibition of both COX 1 and COX 2 , with an IC 50 of 30 microgml ( 1 ) and 5 . 3 10 10 ( 1 ) microgml ( 1 ) , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression was assessed by Western blot analysis . ^^^ COX 1 or COX 2 selective inhibitors used alone did not induce IBD in IL 10 ( / ) mice . ^^^ However , the combination of COX 1 and COX 2 selective inhibitors did induce colitis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition with ibuprofen and nimesulide ( COX 2 selective ) was instituted . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have shown previously in a model of metastatic breast cancer that murine mammary tumor cells express both cyclooxygenase 1 ( Cox 1 ) and Cox 2 isoforms . ^^^ Growth and metastasis of these tumors in syngeneic hosts are inhibited by either selective Cox 1 ( SC 560 ) or selective Cox 2 ( celecoxib ) inhibitors . ^^^ We now report that either selective Cox 1 or Cox 2 drugs inhibited cell replication , but only at concentrations that are no longer selective for either isoform . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compound 7 , N ( 3 phenoxy 4 pyridinyl ) trifluoromethanesulfonamide , showed in vitro ( whole blood assay ) a strong inhibitory activity on the two cyclooxygenase ( COX ) enzymes ( IC ( 50 ) ( COX 1 ) = 2 . 2 microM and IC ( 50 ) ( COX 2 ) = 0 . 4 microM ) , being more active but less COX 2 selective than nimesulide . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostanoid synthesis is regulated by the enzyme cyclo oxygenase ( COX ) that is present in at least two isoforms : COX 1 , the constitutive form , and COX 2 , the inducible form . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We conclude that hypoalgesia is expressed only over a critical range of COX 2 inhibition and that concomitant inhibition of COX 1 prevents expression of hypoalgesia , although hyperalgesia is still prevented . 8 Our results suggest a novel anti nociceptive pathway mediating hypoalgesia , involving COX 2 selectively and having a clear peripheral component . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Estrogen induced responses in vascular cells have been shown to influence prostaglandins and cyclooxygenase ( COX ) , a key enzyme in the production of prostaglandins , with two isoforms , COX 1 and COX 2 . ^^^ Using a double blind placebo controlled design , we assessed skin blood flow in 32 healthy , postmenopausal women by laser Doppler velocimetry with direct current iontophoresis of ACh and sodium nitroprusside before and after 6 wk treatment periods with aspirin ( a nonspecific COX 1 and COX 2 inhibitor ) , diclofenac ( predominantly a COX 2 inhibitor , which also inhibits COX 1 ) , celecoxib ( a specific COX 2 inhibitor ) , given at anti inflammatory doses , or placebo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An LS diet enhanced vascular expression of cytochrome P 4504A and COX 2 in arcuate and interlobular arteries ; COX 1 was unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All tested hydroxylamines and N , O diacetyl hydroxylamines clearly inhibited both COX 1 and COX 2 enzyme activities with IC ( 50 ) values of 1 . 9 28 . 7 and 1 . 6 2 . 9 micro M against COX 1 and COX 2 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate in vivo activity in dogs of meloxicam or aspirin , previously shown in vitro to be a selective cyclooxygenase 2 ( COX 2 ) inhibitor ( COX 1 sparing drug ) , or a nonselective COX inhibitor , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE 2 levels increased rapidly following treatment with fsAbeta , an effect that was prevented by SB 202190 , a selective inhibitor of p 38 mitogen activated protein kinase ( p 38 MAPK ) , and by NS 398 , which preferentially inhibits cyclooxygenase 2 ( COX 2 ) compared to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
No differences in the levels of COX 1 , COX 2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients . ^^^ Sodium salicylate was an ineffective inhibitor of COX 1 , COX 2 or LO activity in blood from both aspirin sensitive and tolerant patients . 4 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The TRAIL mediated COX 1 up regulation was accompanied by a significant increase of the PGE ( 2 ) synthesis and release , which was suppressed by the COX 1 inhibitor valeryl salicylate but not by the COX 2 inhibitor NS 398 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cyclin D 1 and cyclooxygenases ( COX 2 and COX 1 ) was detected using semi quantitative RT PCR , and the production of prostaglandin E 2 ( PGE 2 ) was measured by ELISA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) enzyme system is composed of two isoenzymes , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In freely moving rats , two independent polyclonal antibodies were used which neutralize COX 1 and COX 2 . ^^^ Peripheral pretreatment with an antipyretic dose of dexamethasone which prevents COX 2 expression , or the microinjections into the AH / POA of either anti COX 1 or anti COX 2 , blocked the febrile response induced by RANTES but not that induced by MIP 1beta . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Hepatic detection of COX gene expression by RT PCR revealed that COX 2 but not COX 1 was upregulated following BDL , and this upregulation was confirmed at the protein level by Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX , COX 1 and COX 2 , have been identified by molecular biological methods . ^^^ The amino acid sequence homology between COX 1 and COX 2 is about 60 % for the human enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Kinetic investigations indicate that the time dependence of binding and inhibition of COX 1 and COX 2 by diarylheterocycles is more complex than originally postulated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Distinct functions of COX 1 and COX 2 . ^^^ The enzymes that convert arachidonic acid to prostaglandin H 2 are named cyclooxygenase 1 ( COX 1 ) and COX 2 . ^^^ The properties of COX 1 are different from those of COX 2 . ^^^ It was originally thought that the function of COX 1 was involved in physiological phenomena , whereas that of COX 2 was involved in various pathologies . ^^^ This chapter focuses on the distinct functions of COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Phenotypes of the COX deficient mice indicate physiological and pathophysiological roles for COX 1 and COX 2 . ^^^ The development of mice deficient in either cyclooxygenase 1 ( COX 1 ) or COX 2 , as well as mice deficient in both COX isoforms , has provided models to elucidate the physiological and pathophysiological roles of these enzymes . ^^^ The findings obtained with the COX deficient mice suggest that COX 2 may be more important than COX 1 for supplying prostaglandins ( PGs ) to maintain tissue homeostasis . ^^^ Studies with the COX deficient mice suggest that in addition to COX 2 selective inhibition , therapeutic advances may also be achieved with COX 1 selective inhibitors which lack gastrointestinal side effects . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These two PGESs display distinct functional coupling with upstream COXs in cells ; cPGES is predominantly coupled with the constitutive COX 1 , whereas mPGES is preferentially linked with the inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using rats in vivo and rat and human blood in vitro , we have examined the roles of COX 1 and COX 2 in the production of PGE 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , we investigated the effect of inhibiting COX 1 or COX 2 on various intestinal events occurring in association with NSAID induced intestinal damage . ^^^ Rats without fasting were treated with indomethacin , SC 560 ( a selective COX 1 inhibitor ) , rofecoxib ( a selective COX 2 inhibitor ) , or SC 560 plus rofecoxib , and the following parameters were examined in the small intestine : the lesion score , the enterobacterial number , myeloperoxidase ( MPO ) and inducible nitric oxide synthase ( iNOS ) activity , and intestinal motility . ^^^ We conclude that inhibition of COX 1 , despite causing intestinal hypermotility , bacterial invasion , and iNOS expression , up regulates the expression of COX 2 , and the PGE 2 produced by COX 2 counteracts deleterious events , and maintains the mucosal integrity . ^^^ This sequence of events explains why intestinal damage occurs only when both COX 1 and COX 2 are inhibited . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cyclooxygenases ( COX 1 and COX 2 ) in the gastric mucosa was analyzed using Western blotting and immunohistochemical staining . ^^^ Lansoprazole dose dependently increased the serum gastrin concentration and enhanced the mucosal expression of COX 2 but not that of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Hypoxic inhibition of proliferation was attenuated by incubation with indomethacin ( 10 micro M ) , or the COX 2 antagonist , NS 398 ( 10 micro M ) , but not by the COX 1 antagonist , valeryl salicylate ( 0 . 5 mM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We compared AECs isolated from wild type ( WT ) , COX 1 knockout ( KO ) , and COX 2 KO mice to determine the contribution of COX isoforms to AEC PGE ( 2 ) synthesis and capacity for suppression of fibroblast proliferation in co cultures . ^^^ WT AECs constitutively expressed both COX 1 and COX 2 isoforms by immunoblot analysis . ^^^ COX 1 KO cells and WT cells comparably augmented PGE ( 2 ) synthesis following incubation with lipopolysaccharide or interleukin 1 , whereas COX 2 KO cells were unable to do so . ^^^ When co cultured with WT murine lung fibroblasts , AECs from WT and COX 1 KO animals suppressed serum induced fibroblast proliferation , whereas COX 2 deficient AECs caused a modest enhancement in fibroblast proliferation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The description of two different arachidonic acid cyclo oxygenases ( COX ) about a decade ago , designated COX 1 and COX 2 , and the incorporation into the therapeutic armamentarium of more selective enzyme inhibitors for the control of inflammation and pain , has led to an improved understanding of the pathogenesis of adverse reactions to NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These cucurbitacins were evaluated for their inhibitory effects on the growth of human colon ( HCT 116 ) , breast ( MCF 7 ) , lung ( NCI H 460 ) , and central nervous system ( CNS ) ( SF 268 ) cancer cell lines , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) enzymes and on lipid peroxidation . ^^^ Ibuprofen , naproxen and vioxx , commercial antiinflammatory drugs , were tested as controls for the inhibition of COX 1 and COX 2 enzymes at concentrations of 2 . 1 , 2 . 5 and 1 . 67 microg / ml , respectively . ^^^ Ibuprofen and naproxen exhibited 59 and 95 % COX 1 , and 53 and 79 % COX 2 inhibitory activities , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX enzymes exist in an inducible form COX 2 , that has been found to be elevated in the AD brain , and a constitutive form COX 1 . ^^^ Both COX 1 and COX 2 are known to be involved in numerous inflammatory activities as well as normal neuronal functions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To assess the compound potency on canine enzymes , canine COX 1 and COX 2 were cloned , expressed , and purified . ^^^ The arachidonic acid Michaelis constants for canine COX 1 and COX 2 were 4 . 8 and 6 . 6 micrometer , respectively , compared with 9 . 6 and 10 . 2 micrometer for ovine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Moreover , TNFalpha , which also stimulates aromatase expression in breast adipose stromal cells , acts to increase the secretion of PGE 2 by these cells , as well as the expression of COX 2 and PGE synthase , but not that of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The identification of two isoforms of COX ( COX 1 or the `` constitutive ' ' isoform and COX 2 or the `` inducible ' ' isoform ) led to the hypothesis that COX 1 derived prostaglandins were involved in regulating physiological functions , whereas COX 2 derived prostaglandins played a major role in inflammation or tissue damage . ^^^ It was assumed that the pharmacological effects of NSAIDs depend on the inhibition of COX 2 , whereas the toxic organ specific effects are linked to the inhibition of COX 1 . ^^^ However , COX 2 plays a physiological role in many tissues and organs , and COX 1 is also involved in inflammatory reactions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is produced as a steady state enzyme , while COX 2 is heavily involved in inflammation and tumorigenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TUNEL staining showed that the COX 2 inhibitor NS 398 ( 30 microM ) blocked KCN induced apoptosis , whereas the selective COX 1 inhibitor valeryl salicylate did not affect the level of apoptotic cell death . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX are known : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Etoricoxib is a cyclo oxygenase ( COX ) 2 selective NSAID with a higher COX 1 to COX 2 selectivity ratio than the other COX 2 selective NSAIDs rofecoxib , valdecoxib or celecoxib . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of the cyclooxygenase enzyme , COX 1 and COX 2 , and the development of COX 2 specific inhibitors as anti inflammatories and analgesics have offered great promise that the therapeutic benefits of NSAIDs could be optimized through inhibition of COX 2 , while minimizing their adverse side effect profile associated with inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The changes of COX 1 , COX 2 activities were determined by substrate fluorescence analysis and the mRNA expressions of COX 1 and COX 2 by RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using quantitative RT PCR and Western blot analyses , we found that expression of COX 2 was markedly increased ( P < 0 . 05 ) in peritoneal macrophages isolated from women with early or severe endometriosis , whereas expression of COX 1 was elevated only in the severe stage ( P < 0 . 05 ) . ^^^ Treatment with interleukin 1beta , tumour necrosis factor alpha or PGE 2 caused a significant increase in COX 2 ( P < 0 . 05 ) but not COX 1 expression in peritoneal macrophages isolated from disease free women . ^^^ In contrast , these agents had no substantial effect on COX 1 and COX 2 expression in peritoneal macrophages from women with endometriosis . ^^^ Elevated expression of both COX 1 and COX 2 in peritoneal macrophages may contribute to the increased peritoneal fluid PGE 2 concentrations and may thus play an important role in the development of endometriosis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whether non steroidal anti inflammatory drug ( NSAID ) induced suppression of bone ingrowth is due to cyclooxygenase 1 ( COX 1 ) inhibition , cyclooxygenase 2 ( COX 2 ) inhibition , or through a yet unidentified pathway is unknown . ^^^ In this study , the effects of a non specific COX 1 and COX 2 inhibitor , versus a specific COX 2 inhibitor on bone ingrowth and tissue differentiation are examined in vivo . ^^^ After a 6 week period for osseointegration of the chamber , the following oral treatments were given for 4 weeks each , followed by a harvest in each case : drinking water with no NSAID ( control 1 ) , Naproxen sodium a COX 1 and COX 2 non specific inhibitor at a dose of 110 mg / kg / day in the drinking water , drinking water with no NSAID ( control 2 ) , and Rofecoxib a COX 2 inhibitor at a dose of 12 . 5 mg / day inserted directly into the rabbit ' s mouth . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When considered in conjunction with previous data on carprofen , the present findings indicate that carprofen is not a selective inhibitor of cyclooxygenase ( COX ) isoenzymes , COX 1 and COX 2 in the horse , although it may show some preference for COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the chemopreventive effect of celecoxib on 7 , 12 dimethylbenz [ a ] anthracene ( DMBA ) induced rat mammary tumours and also the expression and immunolocalization of cyclooxygenase 1 ( COX 1 ) and COX 2 in the various stages of rat mammary carcinogenesis . ^^^ Our results suggest that COX 1 and COX 2 expression in tumour cells and stromal cells play an important role in the various stages of DMBA induced rat mammary carcinogenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two cyclooxygenase ( COX ) isoenzymes , a constitutive COX 1 , serving homeostatic prostanoid synthesis , and an inducible COX 2 , responsible for proinflammatory prostanoid production , led to the development of new non steroidal anti inflammatory drugs ( NSAIDs ) , the selective COX 2 inhibitors , promising minimal NSAID typical toxicity with full anti inflammatory efficacy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cytosolic phospholipase A 2 ( cPLA 2 ) , cyclooxygenase 1 ( COX 1 ) , and cyclooxygenase 2 ( COX 2 ) regulate the formation of physiologically active prostaglandins , the production of which is known to be elevated in several renal disorders . ^^^ Renal COX 2 was detected only in the rats and was 58 % lower in diseased kidneys of 70 day old male Han : SPRD cy rats , indicating that cPLA 2 is coupled to COX 1 in the kidney . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoenzymes of COX have been identified : COX 1 and COX 2 . ^^^ Whereas COX 1 is expressed constitutively in most tissues and responsible for tissue homeostasis , COX 2 is inducible and plays an important role in inflammation and tumorigenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All isolates as well as pure linoleic , oleic and stearic acids were evaluated for their inhibitory effects against both cyclooxygenases 1 ( COX 1 ) and 2 ( COX 2 ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of the two isoenzymes of cyclooxygenase COX 1 and COX 2 and their separate functions , localization and regulation , has initiated the search for new and more selective inhibitors of prostaglandin biosynthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 2 expression in PC 3 High Invasive cells was approximately 3 fold higher than in PC 3 Low Invasive cells while the COX 1 expression was similar in both cell sublines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TXA ( 2 ) production , COX 1 and COX 2 mRNA expression , and immunostaining for TXA ( 2 ) synthase were evaluated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
According to a popular hypothesis , COX 1 generates ' good ' prostaglandins for physiological ' housekeeping ' functions like gastrointestinal ( GI ) mucosal integrity and regulation of renal blood flow , while COX 2 forms the ' bad ' prostaglandins responsible for inflammatory symptoms . ^^^ Similarly , the selective inhibition of either COX 1 or COX 2 does not elicit GI damage , but inhibition of both enzymes is necessary for GI mucosal damage to develop . ^^^ The synthesis of endothelial prostacyclin is mainly driven by COX 2 , so that the selective COX 2 inhibition may bias vascular prostaglandin synthesis in favour of COX 1 derived thromboxane A ( 2 ) in platelets , leading to a prothrombotic outcome . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , NS 398 , a specific COX 2 inhibitor , and indomethacin , a COX 1 and COX 2 inhibitor , were administered 24 h after chloroform dosing to determine their effect on liver injury in Sprague Dawley rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because of the different actions of COX 1 and COX 2 , selective COX 2 inhibitors were expected to reduce adverse reactions such as gastrointestinal disorders . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We hypothesized that PGE 2 production by activated macrophages is dependent upon the induction of COX 2 , not upon the constitutive isozyme , COX 1 . ^^^ When we evaluated the expression of COX 1 and COX 2 in titanium alloy particle stimulated human macrophages , the expression of COX 2 mRNA was up regulated by the particles , on the other hand , the expression of COX 1 mRNA was not affected . ^^^ These results provide strong evidence that PGE 2 production by particle stimulated macrophages is dependent upon the induction of COX 2 , not COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study examines the stimulation and inhibition of COX 1 and COX 2 in homogenates of mouse and rabbit tissues and in J774 . 2 cultured mouse macrophages . ^^^ The order of potency of paracetamol on COX 1 or COX 2 in tissue homogenates was as follows : lungs > spleen > brain > J774 . 2 cells > stomach mucosa . ^^^ CONCLUSIONS : These data support the hypothesis that paracetamol selectively inhibits a COX enzyme which is different from COX 1 or COX 2 and may be a variant of COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : C myc was studied in cyclooxygenase ( COX ) 2 associated granulosa cell apoptosis , METHODS : Granulosa cells ( N = 5 cases ) were incubated for 24 h in either 1 or 50 microM COX 2 inhibitor , 1 or 50 microM COX 1 / COX 2 inhibitor , negative or positive controls Single primer polymerase chain reaction of c myc exon 1 were performed . ^^^ Cell viability decreased with COX 1 and COX 2 inhibition . ^^^ CONCLUSIONS : Inhibition of both COX 1 and COX 2 initiated apoptosis without disrupting c myc suggesting a protective effect on c myc . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study examined the functional selectivity of nicotine for nicotinic acetylcholine receptors in the stimulation of the hypothalamic pituitary adrenal ( HPA ) axis , the effect of social crowding stress on HPA response to nicotine and the involvement of prostaglandins synthesized by constitutive cyclooxygenase ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) in the nicotine induced HPA response in rats crowded ( 24 per a box instead 7 ) for 7 days . ^^^ Prostaglandins , generated by COX 1 but not by COX 2 isoenzyme , are of crucial significance in the nicotine induced ACTH and corticosterone secretion in both control and stressed rats . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin endoperoxide H 2 ( PGH 2 ) is generated from arachidonic acid by either constitutive ( COX 1 ) or inducible ( COX 2 ) cyclooxygenases . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The transcription of the DP , EP 1 , EP 2 , EP 3 , EP 4 , FP , IP and TP prostanoid receptor genes as well as the COX 1 and COX 2 enzyme genes was investigated using reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ The COX 2 gene was found to be transcribed , but the COX 1 gene less consistently . ^^^ Surprisingly , the COX 2 rather than the COX 1 gene , was found to be transcribed in the melanocytes . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the expression of COX 2 , cyclooxygenase 1 ( COX 1 ) , nitric oxide synthase 2 ( NOS 2 ) and nitric oxide synthase 3 ( NOS 3 ) in normal proliferative and secretory human endometrium , and in endometrial adenocarcinoma . ^^^ Immunohistochemistry was used to investigate the expression of COX 1 , COX 2 , NOS 2 and NOS 3 . ^^^ CONCLUSIONS : The expression of the inducible COX 2 but not of COX 1 is stimulated in the glandular epithelium of proliferative endometrium and in the cancer cells of human endometrial adenocarcinoma , in particular in those in the borders of carcinoma and spreading into lymphatic vessels . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cox 2 mRNA but not cox 1 was decreased by the AS , but not by meloxicam or in CO treated colitic animals . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunoblot analysis showed a 60 % reduction of COX 1 and COX 2 polypeptides . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study was designed to investigate the role of COX in the development and progression of bladder cancer through examining the expression of COX 1 and COX 2 in human bladder cancer tissue , normal bladder mucosa , and cystitis tissue . ^^^ METHODS : Reverse transcriptase polymerase chain reaction ( RT PCR ) and immunohistochemistry ( Envision method ) were applied to detect the mRNA and protein expression of COX 1 and COX 2 in bladder transitional cell carcinoma ( BTCC ) , tissue adjacent to cancer , normal bladder mucosa , and chronic cystitis tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The gene content in the latter two mtDNAs is almost identical to that of the completely sequenced S . pombe mtDNA , which encodes 25 tRNA species , the large and small mitochondrial ribosomal RNAs ( rnl and rns ) , the RNA component of mitochondrial RNaseP ( rnpB ) , mitochondrial small subunit ribosomal protein 3 ( rps 3 ) , cytochrome oxidase subunits 1 , 2 and 3 ( cox 1 , cox 2 and cox 3 ) and ATP synthase subunits 6 , 8 and 9 ( atp 6 , atp 8 and atp 9 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
One of these , triacetylsalicylhydroxamic acid ( TriAcSHA ) was more effective than aspirin and O acetylsalicylhydroxamic acid in inactivating both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX isoforms ( COX 1 and COX 2 ) constitutively are expressed in the adult mammalian kidney and contribute to the biosynthesis of prostaglandins ( PGs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Microsomal PGES 1 ( mPGES 1 ) , identical to MGST 1 L1 , is an inducible perinuclear enzyme that is functionally linked with COX 2 in marked preference to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Interactions among COX 1 , COX 2 , and COX 3 mRNA specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae . ^^^ Mitochondrial translation of the COX 1 , COX 2 , and COX 3 mRNAs is activated mRNA specifically by the nuclearly coded proteins Pet309p , Pet111p , and the concerted action of Pet54p , Pet122p , and Pet494p , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As a surrogate marker of diclofenac activity , the ex vivo formation of prostaglandin E 2 and thromboxane B 2 , which reflects COX 2 and COX 1 activity , was measured . ^^^ Marked diclofenac mediated inhibition of COX 1 and COX 2 activity was detected in all individuals independent of CYP2C9 genotype . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) exists as two isoforms : COX 1 , which is constitutively expressed in most cell types ; and COX 2 , which is inducible by lipopolysaccharide ( LPS ) and cytokines in a variety of cell types . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , increased prostaglandin synthesis in Hp infected patients appears to be COX 1 mediated rather than COX 2 . ^^^ Furthermore , failure of endotoxaemia treated sample to produce more PGE ( 2 ) in the face of enhanced COX 2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX 1 mediated . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of angiotensin AT ( 1 ) receptors by candesartan from postnatal day 1 to day 5 increased COX 2 mRNA ( 2 . 5 fold ) , protein , and distribution , renin mRNA ( 7 fold ) and PRC ( 20 to 70 fold ) , but had no influence on COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effects of clinorotation on production of PGE 2 and expression of COX 1 and COX 2 mRNA in MC3T3 E 1 mouse osteoblasts ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Valeryl salicylate , a selective COX 1 inhibitor , did not significantly inhibit this contraction , whereas N ( 2 cyclohexyloxy 4 nitro phenyl ) methanesulfonamide , a selective COX 2 inhibitor , abolished this contraction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Serum thromboxane ( TX ) B 2 and plasma prostaglandin ( PG ) E 2 levels were measured by specific radioimmunoassays as indices of platelet COX 1 and monocyte COX 2 activity , respectively . ^^^ Valdecoxib , etoricoxib , DFU and DFP inhibited platelet COX 1 and monocyte COX 2 with the following COX 1 / COX 2 IC 50 ratios : 61 . 5 , 344 , 660 and 1918 , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Biochemical analyses of the primary splenic tumor in rofecoxib treated mice showed no alteration in COX 1 expression , but significant decreases in the expression of the tumor promoting proteins COX 2 , cyclin D 1 , cytosolic beta catenin , matrix metalloproteinases 2 and 9 , and vascular endothelial cell derived growth factor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , despite this evidence , therapeutic studies investigating nonsteroidal anti inflammatory drugs ( NSAIDs ) , including cyclooxygenase 1 ( COX 1 ) and COX 2 inhibitors and steroids , do not support this hypothesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL 1 beta ( 1 nM ) induced mRNAs for cyclooxygenase 2 ( COX 2 ) , MMP 1 , 3 , 13 and aggrecanase 1 as well as IL 1 beta and IL 6 , whereas mRNAs for COX 1 and MMP 2 were expressed constitutively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PEMFs effect on TGF beta 1 was via a prostaglandin dependent mechanism involving Cox 1 but not Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recognition of the two distinct COX isoforms prompted development of drugs that selectively block the activity of COX 2 , thus providing pain relief and reducing inflammation while sparing COX 1 , the enzyme apparently responsible for most protective prostaglandin synthesis in the mucosa of the stomach and duodenum . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases 1 and 2 ( COX 1 and COX 2 , also known as prostaglandin H 2 synthases 1 and 2 ) catalyze the committed step in prostaglandin synthesis . ^^^ COX 1 and 2 are of particular interest because they are the major targets of nonsteroidal antiinflammatory drugs ( NSAIDs ) including aspirin , ibuprofen , and the new COX 2 selective inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The enzymes included cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , phospholipase A ( 2 ) ( PLA ( 2 ) ) , 5 lipoxygenase ( 5 LO ) and 12 lipoxygenase ( 12 LO ) . ^^^ The most potent COX 1 , COX 2 and 5 LO inhibition was observed in the extract of T . wilfordii with the IC ( 50 ) values of 27 , 125 and 22 microg / ml , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Role of cyclooxygenases COX 1 and COX 2 in modulating adipogenesis in 3T3 L 1 cells . ^^^ Two COX isoforms have been identified , COX 1 , the constitutive form , and COX 2 , the inducible form . ^^^ COX 2 was found to be expressed in undifferentiated 3T3 L 1 cells and down regulated during differentiation , whereas the cellular level of COX 1 remained relatively constant . ^^^ Tumor necrosis factor alpha ( TNFalpha ) significantly up regulated COX 2 expression ( approximately 2 fold ) in differentiating 3T3 L 1 cells , whereas similar effect was not observed with COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : 6 Keto PGF 1 alpha and PGE 2 were assayed by radioimmunoassay ( RIA ) method ; mRNA expression of COX 1 and COX 2 were assayed by reverse transcription polymerase chain reaction ( RT PCR ) method . ^^^ The ratio of IC 50 COX 1 / IC50 COX 2 of compound A and B are 1 , 000 and 560 , respectively . ^^^ They both can inhibit COX 2 mRNA expression in cultured rat peritoneal macrophages stimulated with LPS ( 1 microgram . mL 1 ) , and have no effect on COX 1 mRNA expressions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that : ( 1 ) SC 236 inhibited growth of gastric cancer cells mainly by inducing apoptosis ; ( 2 ) SC 236 induced 15 LOX 1 expression and increased endogenous 13 S HODE product , instead of 15 S HETE during apoptosis ; ( 3 ) SC 236 did not affect expression of COX 1 , COX 2 , 5 LOX and 12 LOX ; and ( 4 ) 15 LOX 1 inhibition suppressed SC 236 induced apoptosis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : The interactions of the compound ZZ 122 with cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) were modeled by docking method . ^^^ RESULTS : According to the binding pattern , intermolecular energy and capacity to form H bond , it was easy for ZZ 122 to bind to COX 2 and not easy to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : The purpose of the present study was to evaluate the effect of a relatively selective cyclooxygenase ( COX ) 2 inhibitor ( nimesulide ) and non selective COX 1 / COX 2 inhibitor ( naproxen ) used as an adjunct to non surgical ( scaling and root planing [ SRP ] ) periodontal therapy in chronic periodontitis patients on the gingival tissue ( GT ) levels of prostaglandin ( PG ) E 2 and PGF2alpha . ^^^ The determination of GT levels of COX 1 and COX 2 enzymes as well as PGE 2 and PGF2alpha in long term studies may provide further support for the adjunctive use of selective COX 2 inhibitors in treatment of chronic periodontitis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The in vitro inhibitory activity of the most active compounds towards human COX 1 and COX 2 enzymes was also estimated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This defect was associated with reduced expression of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) , key enzymes in the biosynthesis of PGE ( 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 ) through its reducing activity , that is influenced by the different cellular levels of peroxides . 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In terms of renal function , both Type 1 and Type 2 cyclooxygenase ( COX 1 and COX 2 ) are expressed constitutively in the kidney . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We present the temporal and regional expression patterns of mRNAs for the two Gs coupled PGE receptors , EP 2 and EP 4 , and for COX 1 and COX 2 in mouse periovulatory follicles and oviducts during superovulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase isoforms , COX 1 and COX 2 , are the rate limiting enzymes in the biosynthesis of prostaglandin E ( 2 ) , a major prostaglandin involved in epidermal homeostasis and repair . ^^^ Although COX 1 expression in keratinocytes remained unchanged during wound healing , COX 2 expression was induced coincidentally with keratinocyte proliferation and keratin 6 expression , suggesting a role for COX 2 in epidermal repair . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The drug did not affect the expression of the enzymes involved in PGE ( 2 ) synthesis , i . e . , COX 1 , COX 2 , and microsomal PGE synthase , or the release of the precursor arachidonic acid ( AA ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 1 selective inhibitor SC 560 and the COX 2 selective inhibitor NS 398 were equally effective , indicating that both isoforms are involved . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cells are permeabilized with FACS Lysing Solution ( FLS ) containing saponin ( Sap ) , stained intracellularly with COX 2 and COX 1 monoclonal antibodies ( mAbs ) and analyzed flow cytometrically . ^^^ The specificity of COX 2 and COX 1 binding is demonstrated by competitive inhibition studies in cells and binding studies on protein conjugated beads . ^^^ In addition , a two color reagent combination is described which simultaneously detects COX 2 and COX 1 . ^^^ We conclude that specific , intracellular COX 1 and COX 2 expression can be readily identified by flow cytometry in whole blood monocytes and cultured cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The AA released by cPLA ( 2 ) gamma was metabolized further to prostaglandin E ( 2 ) via cyclo oxygenase 1 ( COX 1 ) in the immediate response , and via COX 2 in the delayed response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The left intrapulmonary artery and bronchi were removed and mounted on a wire myograph , and lung expression , content , and immunolocalization of cyclooxygenases COX 1 and COX 2 were evaluated . ^^^ The lung mRNA levels of COX 1 and COX 2 were increased in the CDH and nitrofen groups . ^^^ COX 1 vascular and airway immunostaining , as well as COX 1 and COX 2 lung protein content , were increased in the CDH group . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Some of these compounds also inhibited COX 1 and COX 2 in human monocytes and 4b showed selectivity for COX 2 inhibition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The diastereo and enantioselectivity has been explained by molecular modelling of RR , SS and RS compounds into COX 1 and COX 2 binding sites . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A majority of specimens exhibited elevated levels of COX 1 , not COX 2 , mRNA , and protein compared with normal ovarian tissue . ^^^ Selective inhibition of COX 1 , not COX 2 , inhibited arachidonic acid stimulated vascular endothelial growth factor production , which could be reversed by cotreatment with prostaglandin E ( 2 ) . ^^^ Clinical studies testing the efficacy of COX inhibition as adjuvant therapy for ovarian cancer may see more beneficial effects with adjuvant therapy with either a COX 1 selective or nonselective cyclooxygenase inhibitor as compared with a COX 2 selective drug . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of cyclooxygenase ( both COX 1 and COX 2 ) has also been examined immunohistologically . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists as two isoforms , namely COX 1 and COX 2 with distinct tissue distribution and physiological functions . ^^^ COX 1 is constitutively expressed in many tissues and cell types and is involved in normal cellular physiological functions whereas COX 2 is pro inflammatory in nature and is inducible by mitogens , cytokines , tumor promoters and growth factors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The contribution of phosphorylated p 38 and p44 / 42 MAPK on COX 1 and COX 2 expression was also examined with MAPK inhibitors ( p 38 , SB 203580 and p44 / 42 , PD 98056 ) . ^^^ ET 1 resulted in transient increases in ppET 1 , COX 1 , and COX 2 gene and protein expression and release of 6 keto PGF ( 1alpha ) and PGE ( 2 ) ( P < 0 . 05 ) . ^^^ Although increased ppET 1 was regulated by both ET ( A ) and ET ( B ) , COX 2 expression was upregulated only by ET ( A ) ; COX 1 expression was unaffected by either antagonist . ^^^ ET 1 treatment resulted in transient phosphorylation of p 38 and p44 / 42 MAPK ; inhibitors of these MAPKs suppressed expression of COX 2 but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Among the compounds tested , only the 3 ( p methylsulfonylphenyl ) substituted thiophene derivatives 17 and 22 , showed a certain COX 2 inhibitory activity , accompanied by an appreciable COX 2 versus COX 1 selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
On ovariectomy induced parturition in these mice , uterine COX 2 mRNA expression was drastically induced in the myometrium , whereas COX 1 mRNA expression in the endometrial epithelium decreased . ^^^ The concomitant administration of progesterone with ovariectomy resulted in a delay in parturition and the disappearance of both the increase in COX 2 mRNA and the decrease in COX 1 mRNA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide , we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) and endothelial ( NOS 3 ) and inducible ( NOS 2 ) nitric oxide synthase in rat lungs . ^^^ The lungs were ventilated with 70 % oxygen for 3 h after the insult , and the level of COX 1 , COX 2 , NOS 2 , and NOS 3 mRNA in lung tissue was analyzed by Northern blot hybridization . ^^^ COX 1 and NOS 3 were clearly expressed in the lungs of control rats , whereas the level of COX 2 and NOS 2 expression was minimal . ^^^ Meconium administration did not affect the expression of COX 1 , but COX 2 expression was up regulated in the respiratory epithelium and alveolar macrophages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exposure of these cells for 1 h to 100 nM AngII , ET 1 or EGF resulted in an increase in prostacyclin formation which was abolished by the COX 2 specific inhibitor NS 398 ( 1 microM ) , while the COX 1 inhibitor valeryl salicylate ( 5 microM ) had no effect . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 levels were increased in lungs of both COX 1 / and COX 2 / mice relative to wild type . ^^^ These data suggest that genetic deficiency of COX 1 but not COX 2 modulates T cell recruitment , Th 2 cytokine secretion , and lung function in the allergic airway . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Oral administration of the nonselective cyclooxygenase ( COX ) inhibitor indomethacin ( 20 mg / kg ) , the COX 1 inhibitor 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ( SC 560 ) ( 20 mg / kg ) , or the COX 2 inhibitor rofecoxib ( 1 20 mg / kg ) antagonized the gastroprotective effects of 16 , 16 dimethyl prostaglandin ( PG ) E 2 ( 75 ng / kg p . o . ) and 20 % ethanol in rats . ^^^ The findings show that inhibition of COX 1 or COX 2 antagonizes not only adaptive gastroprotection by 20 % ethanol but also the protective effect of exogenous PG in a cromakalimsensitive manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 2 expression in NSCLC cells was 75 % ( 3 / 4 ) and the COX 1 expression in NSCLC cells was 100 % ( 4 / 4 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of COX , referred to as COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compound 13 is 384 fold and 19 is more than 470 fold selective towards COX 2 compared to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LPS markedly increased the expression of COX 2 and release of PGE ( 2 ) in a time and concentration dependent manner , whereas COX 1 remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , resveratrol ( selective COX 1 blocker ) , and COX 2 antagonists , nimesulide , NS 398 , DuP 697 , and L 752860 , attenuated the additional inhibitory effects of gut manipulation following laparotomy in a dose dependent manner . ^^^ CONCLUSION : In addition to NO synthesized by constitutive NOS ( cNOS ) , prostaglandins produced by both COX 1 and COX 2 participate in the pathogenesis of PI , albeit in different pathological mechanisms . ^^^ Thus laparotomy stimulated COX 2 activity , whereas gut manipulation led to an excessive cNOS activity and prostaglandin synthesis by COX 1 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two compounds ( celecoxib and valdecoxib ) from the diarylheterocycle class of cyclooxygenase inhibitors were radiolabeled and used to characterize their binding to cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , several single point variants of COX 2 ( Val523Ile , Tyr355Ala , Arg120Ala , Arg120Gln , Arg120Asn ) and one triple point variant of COX 2 [ Val523Ile , Arg513His , Val434Ile ( IHI ) ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , a recent progress of the understanding about COX physiology has revealed that NSAIDs cause gastric mucosal injury by inhibiting not only COX 1 but also COX 2 in the stomach . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
On the level of mRNA expression , the cytokine tumor necrosis factor alpha ( TNFalpha ) , lactoferrin ( Lf ) , and specific key enzymes of leukotriene and prostaglandin biosynthesis , 5 lipoxygenase ( 5 LO ) , and cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) , respectively , were determined . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two COX isoforms , COX 1 ( constitutive form ) and COX 2 ( inducible form ) are both abundantly expressed in renal inner medulla at basal state , raising a question of which COX isoform may mediate the known functions of PGs in the region . ^^^ It is likely that in response to various insults that are detrimental to renal medulla , the induction of PG synthesis may become more dependent on COX 2 than COX 1 , and this phenomenon may be relevant to the cytoprotective response against the insults . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An important role for COX 2 derived prostanoids in regulation of renin expression and secretion has also been determined by using mice with selective genetic deletion of either the COX 1 or COX 2 gene . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to measure and compare COX 1 and COX 2 expression in normal and hamartomatous tissue of PJS patients . ^^^ METHODS : We measured COX 1 and COX 2 protein expression in normal and hamartomatous GI tissues from affected PJS individuals and compared it with that in normal controls . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prothrombotic genetic variations that may contribute to ASA resistance , and increased risk of cardiovascular events may involve : ( 1 ) a polymorphism on the cyclooxygenase 1 ( COX 1 ) gene affecting Ser 529 ; ( 2 ) overexpression of COX 2 mRNA on platelets and endothelial cells ; ( 3 ) polymorphism PLA1 / A2 of the gene encoding glycoprotein IIIa ( GPIIIa ) ; and ( 4 ) the homozygous 807T ( 873A ) polymorphism allied with increased density of platelet GP Ia / IIa collagen receptor gene . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Plaques were subjected to analysis of COX 1 , COX 2 , mPGES , MMP 2 and MMP 9 , lipid and oxidized LDL ( oxLDL ) content , and collagen content by immunocytochemistry , Western blot , and reverse transcription polymerase chain reaction , whereas zymography was used to detect MMP activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot experiments revealed that infection was accompanied by increased cyclooxygenase 2 ( Cox 2 ) expression , with no change in Cox 1 levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The relative importance of COX 1 and COX 2 isoforms is under active investigation . ^^^ In the terminal distal convoluted tubule , connecting tubule , and cortical and medullary collecting ducts , a significant COX 1 signal was colocalized with PGES ; COX 2 was not found in these sites . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 / 2 ( COX 1 / COX 2 ) and 5 lipoxygenase ( 5 LOX ) inhibitors of the 6 , 7 diaryl 2 , 3 1H dihydropyrrolizine type . ^^^ A series of 6 , 7 diaryl 2 , 3 1H dihydropyrrolizines was prepared as COX 1 / COX 2 and 5 LOX inhibitors . ^^^ The inhibition of COX 1 was evaluated using intact bovine platelets as the enzyme source , whereas LPS stimulated human monocytes served as the enzyme source for inducible COX 2 . ^^^ The determination of arachidonic metabolites was performed by HPLC for COX 1 and RIA for COX 2 . ^^^ The balance between COX 1 / COX 2 and 5 LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6 and 7 position of the pyrrolizine nucleus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Treatment of animals with COX 1 inhibitor had no effect on T cell proliferation response in both septic and sterile groups , whereas COX 2 inhibitor abrogated the decrease in T cell proliferative response in the septic group . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 2 is cytokine inducible , COX 1 is expressed by macrophages / microglial cells that accumulate in pathological foci . ^^^ We analyzed the localization of COX 1 and COX 2 in postmortem cortex slices of eight patients who died with sporadic Creutzfeldt Jakob disease ( CJD ) and four neuropathologically unaltered controls by immunohistochemical double labeling , reverse transcriptase polymerase chain reaction ( RT PCR ) , and Western blotting experiments . ^^^ In healthy brains , COX 1 was expressed by single macrophages / microglial cells and COX 2 by disseminated neurons . ^^^ RT PCR and Western blotting revealed more COX 1 and COX 2 mRNA and protein in one CJD patient than in one control patient . ^^^ These data show that accumulation of COX 1 expressing macrophages / microglial cells and COX 2 expressing neurons might represent important regulatory mechanisms in the complex process of neuronal degeneration in CJD patients . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recently , a specific cyclooxygenase 2 ( COX 2 ) inhibitor , Celecoxib , was developed , which inhibits COX 2 induced inflammation without inhibiting the cytoprotective function of cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To understand the potential role of cyclooxygenase ( COX ) in normal and inflammatory human diseases , we characterized the expression of COX 1 and COX 2 in biopsies of osteoarthritis , atherosclerosis , and cancer . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms , COX 1 and COX 2 , which differ in physiological functions and distribution . ^^^ A human colon carcinoma cell line , COLO 320DM , was transfected with an eukaryotic expression vector ( pEF BOS ) carrying cDNA of either COX 1 or COX 2 . ^^^ Both COX 1 and COX 2 expressing cells exhibited a similar enzyme activity , 8 10 nmol / 10 min / mg of protein . ^^^ A COX inhibitor , indomethacin , suppressed the stimulated growth , increased DNA synthesis and induction of epidermal growth factor receptor in the COX 1 and COX 2 transfected cells . ^^^ These results suggest that not only COX 2 but COX 1 is involved in the proliferation of human colon carcinoma cells through the induction of EGFR . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LPS induced synthesis and release of PGE 2 in liver macrophages : regulation by CPLA 2 , COX 1 , COX 2 , and PGE 2 synthase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Also , renal cyclooxygenase ( COX 1 and COX 2 ) and endothelial NOS ( eNOS ) expression was determined using PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An immunohistochemical survey of nine cases of medullary carcinoma of thyroid including reactivity for Cox 1 and Cox 2 enzymes . ^^^ Slides cut from formalin fixed paraffin embedded tumor tissue from these cases were assessed for the activities of Cox 1 and Cox 2 enzymes by immunohistochemistry as well as by a battery of immunohistochemical stains for intermediate filaments , peptide hormone , and proliferation and promoter antigens . ^^^ Staining for Cox 1 and Cox 2 enzymes was present only in tumorous tissue , not in nontumorous thyroid tissue or C cells . ^^^ Cox 2 staining was not consistently increased over Cox 1 staining ; however , Cox 2 staining bore statistically significant correlations with the expression of low molecular weight keratin , thyroid transforming factor 1 , topoisomerase , and MIB 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Alphavbeta 3 engagement also led to vascular endothelial cell growth factor ( VEGF ) generation and EC proliferation that was attenuated by inhibition of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) participate in growth control ; COX 1 is constitutively expressed in most cells , and COX 2 is an inducible enzyme in response to cellular stimuli . ^^^ Although both COX 1 and COX 2 inhibitors are suppressors of cell proliferation and appear to be chemopreventive agents for tumorigenesis , the molecular mechanisms mediating antiproliferative effect of COX inhibitors are still not well defined . ^^^ This study contrasts and compares the effects of aspirin and celecoxib , inhibitors of COX 1 and COX 2 , in rat hepatoma HTC IR cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is generally considered to contribute to cell homeostasis , whereas COX 2 is thought to mediate inflammatory / immune PG formation . ^^^ Treatment of cells with the non specific COX inhibitor indomethacin , or the specific COX 2 inhibitor NS 398 , prior to mc PAF stimulation completely blocked the PAF induced release of PGE ( 2 ) ; treatment with more selective COX 1 inhibitors ( i . e . piroxicam and SC 560 ) failed to significantly do so . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSION : These data show that COX 1 and COX 2 derived prostaglandins induced by low concentration AA pretreatment reduce the colonic mucosal injury and the increase in the MPO activity in colitis , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of the present study was to determine the effect of social stress and significance of prostaglandins ( PG ) generated by constitutive and inducible cyclooxygenase ( COX 1 and COX 2 ) in the stimulation of hypothalamic pituitary adrenal ( HPA ) axis by corticotropin releasing hormone ( CRH ) under basal and social crowding stress conditions . ^^^ Inhibitors of COX 1 , piroxicam ( 0 . 2 , 2 . 0 , and 5 . 0 mg / kg ) , and COX 2 , compound NS 398 ( 0 . 2 and 2 . 0 mg / kg ) , were administered i . p . 15 min prior to CRH ( 0 . 1 microg / kg i . p . ) to control or crowded rats . ^^^ Therefore , PG generated by COX 1 or COX 2 do not participate to a significant extent in the stimulation of HPA axis by CRH under either basal conditions or during crowding stress . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Qualitative similar results were obtained with resting or thrombin stimulated platelets containing these esterified CLA isomers indicating that these effects occur with cells that contain either the COX 1 or COX 2 isozymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Given the potential utility of COX inhibitors in treating these disorders , we examined the nonselective COX inhibitor flurbiprofen , the specific COX 1 inhibitor valeryl salicylate ( VS ) , and the COX 2 inhibitor N [ 2 ( cyclohexyloxy ) 4 nitrophenyl ] methanesulfonamide ( NS 398 ) for their abilities to protect striatal neurons against a quinolinic acid ( QA ) induced excitotoxic lesion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is a key enzyme in the synthesis of prostaglandins , and 2 isoforms have been identified : COX 1 and COX 2 . ^^^ To determine whether COX expression correlates with biliary histology in patients with AAPBD , the authors investigated the expression of COX 1 and COX 2 in the gallbladder of patients with AAPBD . ^^^ The authors quantified levels of COX 1 and COX 2 by the extent and intensity of staining after immunohistochemistry using anti COX 1 and anti COX 2 antibodies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Using HOC in culture stimulated with interleukin 1 beta ( IL 1beta ) , the effects of GS on NFkappaB activation , nuclear translocation of NFkappaB / Rel family members , COX 1 and COX 2 expressions and syntheses and prostaglandin E 2 ( PGE 2 ) concentration were studied . ^^^ GS also inhibited the gene expression and the protein synthesis of COX 2 induced by IL 1beta , while no effect on COX 1 synthesis was seen . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blotting showed increased 5 lipoxygenase , COX 1 and COX 2 protein levels in ischemic bladder tissues . ^^^ CONCLUSIONS : Chronic ischemia increased bladder 5 lipoxygenase , and COX 1 and COX 2 protein expression , and altered leukotriene and PG production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In view of published evidence that lithium chloride administered chronically to rats , like chronic valproate , reduces AA turnover within brain phospholipids , and that lithium post transcriptionally down regulates COX 2 but not COX 1 protein level and enzyme activity , these observations suggest that mood stabilizers generally modulate the release and recycling of AA within brain phospholipids , and the conversion of AA via COX 2 to PGE 2 and related eicosanoids . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Similar enzymes , different mechanisms : COX 1 and COX 2 enzymes in neurologic disease . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To better define the role of the various prostanoid synthases in the adjuvant induced arthritis ( AIA ) model , we have determined the temporal expression of the inducible PGE synthase ( mPGES 1 ) , mPGES 2 , the cytosolic PGES ( cPGES / p23 ) , and prostacyclin synthase , and compared with that of cyclooxygenase 1 ( COX 1 ) and COX 2 . ^^^ The cPGES / p23 and COX 1 were induced during AIA , but at much lower levels ( 2 to 6 fold ) than mPGES 1 , with the peak of cPGES / p23 expression occurring later than that of COX 2 and PGE ( 2 ) production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As a control to Cox 2 expression , Cox 1 expression was examined . ^^^ Interestingly , in contrast to the down regulated Cox 2 expression , Cox 1 mRNA expression was induced in these four Eker RCs and cell lines . ^^^ Cox 2 and Cox 1 expression were further examined in six additional Eker RCs . ^^^ In total , Cox 2 mRNA expression was down regulated in eight out of ten Eker RCs and cell lines , while Cox 1 mRNA expression was up regulated in nine out of ten Eker RCs and cell lines . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins ( PGs ) originate from the degradation of membranar arachidonic acid by cyclooxygenases ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The conventional NSAIDs that inhibit both cyclooxygenases ( COX 1 and COX 2 ) also induced PPARgamma binding activity . ^^^ In general , however , neither COX 1 nor COX 2 specific inhibitors induced the activation of PPARgamma . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , we also investigated the effects of these NSAIDs on human COX 1 and COX 2 activity . ^^^ Etodolac and meloxicam showed selectivity for human COX 2 over COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Data from animal studies suggest that both non specific and specific inhibitors of cyclooxygenases impair fracture healing but that this is due to the inhibition of COX 2 and not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of COX 1 , the constitutive isoform , is primarily responsible for the adverse gastrointestinal effects of the NSAIDs whereas inhibition of COX 2 , the inducible isoform , accounts for their therapeutic effects . ^^^ There is consistent evidence that COX 1 plays a major role in the early pain response following injury and that analgesia is increased when both COX 1 and COX 2 are inhibited simultaneously . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of GSNO ( 10 500 micro M ) on cell growth , PGE ( 2 ) production , COX 1 / COX 2 protein expression and cell cycle distribution were evaluated . ^^^ GSNO increased PGE ( 2 ) production and induced COX 1 and COX 2 protein expression in a dose and time dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A number of naphthofuranones were synthesized and tested for COX 1 and COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , a number of recent studies raised serious questions about the two central tenets that support this approach , namely that the prostaglandins that mediate inflammation and pain are produced solely via COX 2 and that the prostaglandins that are important in gastrointestinal and renal function are produced solely via COX 1 . ^^^ So , increasing evidence shows that COX 2 ( not only COX 1 ) also plays a physiological role in several body functions and that , conversely , COX 1 ( not only COX 2 ) may also be induced at sites of inflammation . ^^^ Moreover , COX 2 selective NSAIDs have lost the cardiovascular protective effects of non selective NSAIDs , effects which are mediated through COX 1 inhibition ( in addition , COX 2 has a role in sustaining vascular prostacyclin production ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase , the rate limiting enzyme in the production of prostaglandins , exists in two isoforms , the constitutive cyclooxygenase 1 ( Cox 1 ) and the inducible cyclooxygenase 2 ( Cox 2 ) . ^^^ Cox 1 is involved in homeostatic functions while Cox 2 is implicated in various pathological processes such as inflammation and cancer . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase exist in two iso forms ( COX 1 and COX 2 ) . ^^^ It has ben proposed that Non steroidal anti inflammatory drugs ( NSAIDs ) with preferential COX 2 selectivity have fewer renal side effects than drugs with preferential COX 1 selectivity . ^^^ The significance of this remains unclear since nephrotoxicity is relatively uncommon with ibuprofen and , when present is usually rapidly reversible although , ibuprofen has a higher potency against COX 1 than COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , COX 1 and COX 2 protein expression levels were determined in sets of tumor and normal colon tissue . ^^^ Changes were characterized in COX 1 and COX 2 expression within individuals , in relation to such factors as sex , tumor grade , and location in the colorectum . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs ( NSAIDs ) are known to act by inhibiting COX 1 and COX 2 isoenzymes to various degrees . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Eugenol inhibited the proliferation of HT 29 cells and the mRNA expression of COX 2 , but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : To elucidate the role of arachidonic acid metabolism via the cyclooxygenase pathway in different human lung tumors , expression of cyclooxygenase isoenzymes ( Cox 1 and Cox 2 ) and downstream enzymes of prostanoid metabolism was investigated in human non small cell lung cancer and normal human lung tissue by immunohistochemical techniques . ^^^ Endothelial cells of vessels found within or near the tumor show extensive immunostaining of Cox 2 and thromboxane A ( 2 ) synthase , whereas endothelial cells of normal lung specimens , in contrast , expressed Cox 1 and prostacyclin synthase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All the lines were positive for COX 1 protein and mRNA , as evaluated by Western blot and RT PCR , respectively , while only one was positive for COX 2 . ^^^ Cytostatic activity was observed after a 24 h drug exposure and 50 % growth inhibition was reached at concentrations ranging from 165 to 250 micro M in all cell lines , whereas with aspirin the IC 50 was never reached , even at the maximum concentration tested ( 500 micro M ) , and was independent of COX 1 or COX 2 status . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inflammatory process can be influenced by an enzyme known as cyclooxygenase , which exists in two isoforms : COX 1 , the constitutive form , and COX 2 , which is only synthesized in the case of inflammation and has negative side effects . ^^^ To decrease these undesirable effects , current research seeks to discover compounds that selectively inhibit COX 2 versus COX 1 . ^^^ As for COX 2 , cells were first incubated with acetylsalicylic acid to block COX 1 , then stimulation of COX 2 was performed using 8 mcg / ml lipopolysaccharide ( LPS ) for 3 h at 37 degrees C with 50 microM arachidonic acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : Although rofecoxib has very high selectivity for cyclo oxygenase 2 ( COX 2 ) , supratherapeutic rofecoxib concentrations ( > 1000 mg ) inhibit purified human COX 1 in vitro and TXB 2 formation in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mucin assay and western blots for COX 1 and COX 2 were performed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenase ( COX ) catalyzes the committed step in prostaglandin biosynthesis and exists as two related but unique isoforms , COX 1 ( constitutive ) and COX 2 ( inducible ) . ^^^ Studies with the COX 1 and COX 2 knockout mice have demonstrated that COX 2 , but not COX 1 , is crucial for normal ovulation , implantation , and decidualization , suggesting that COX 2 derived PGs are important during the initial stages of pregnancy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It exists in two isoforms : COX 1 which is constitutively expressed and COX 2 which is an inducible form activated by a variety of cytokines during inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of the cyclooxygenase enzymes , COX 1 and COX 2 , has represented a great advance in our understanding of the mechanism of action of NSAIDs and has also elucidated the problem of cross reactivities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mechanotransduction in bone cells proceeds via activation of COX 2 , but not COX 1 . ^^^ We determined which COX isoform , COX 1 or COX 2 , determines loading induced prostaglandin production in primary bone cells in vitro . ^^^ Inhibition of COX 2 activity with NS 398 abolished the stimulating effect of PFF both at 1 h and at 24 h post incubation , while inhibition of COX 1 by SC 560 affected neither the early nor the late response to flow . ^^^ PFF rapidly stimulated COX 2 mRNA expression at 1 h but did not affect COX 1 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prevention of thrombosis and vascular inflammation : benefits and limitations of selective or combined COX 1 , COX 2 and 5 LOX inhibitors . ^^^ Newly developed dual COX 5 lipoxygenase ( 5 LOX ) inhibitors share the anti inflammatory effect and gastric safety of COX 2 inhibitors , but also inhibit COX 1 mediated platelet function and 5 LOX mediated synthesis of gastrotoxic leukotrienes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Surprisingly aspirin , which is selective for COX 1 over COX 2 , and sulindac , which is an equipotent inhibitor of the COX isoenzymes , appear to have a similar anticancer profile to the COX 2 selective NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX ) exists in two isoforms , COX 1 and COX 2 , that direct the synthesis of prostaglandins , prostacyclin and thromboxane . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the effects of COX 1 and / or COX 2 inhibition in a model of chronic esophagitis in rabbits . ^^^ Rabbits were treated with either a selective COX 2 inhibitor ( DFU [ 3 ( 3 Fluorophenyl ) 4 ( 4 Methanesulfonyl ) 5 , 5 Dimethyl 5H Furan 2 One ] ; 30 mg / Kg / day ) , a nonspecific COX inhibitor ( indomethacin ; 2 mg / Kg / day ) , or a COX 1 preferential inhibitor ( piroxicam ; 2 mg / Kg / 12 h ) . ^^^ CONCLUSIONS : COX 1 activity is constitutive in the rabbit esophageal mucosa , but both COX 2 and COX 1 activity are increased under the impact of acidified pepsin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We therefore examined COX 1 and COX 2 genes and COX 2 protein expression and activity ( prostaglandin E 2 [ PGE 2 ] tissue concentration ) in cortical regions of rat brain after exposure to either IH ( 10 % O 2 alternating with 21 % O 2 every 90 seconds ) or sustained hypoxia ( 10 % O 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aspirin effects were apparently unrelated to prostaglandin biosynthesis inhibition , since although these cells were found to express high levels of cyclooxygenase 1 ( COX 1 ) and low levels of COX 2 proteins , they did not produce any measurable net amounts of prostaglandins , based on both utilization of radiolabelled arachidonic acid and the radioimmunoassay of prostaglandins E 2 and F 2 alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study investigated the relative contribution of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation ( PVL ) . ^^^ COX 1 / COX 2 mRNA expression over abdominal aorta and superior mesenteric artery and ( 3 ) . plasma levels of 6 keto prostaglandin F1alpha . ^^^ There were no differences in the COX 2 expression of superior mesenteric artery and COX 1 and COX 2 expressions of abdominal aorta between without and with bleeding groups . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discoveries that cyclooxygenase ( COX ) 2 is an inducible form of COX that is involved in inflammation and that COX 1 is the major isoform responsible for the production of prostaglandins have provided a reasonable basis for the development of specific COX 2 inhibitors as a new class of anti inflammatory agents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The authors investigated the prognostic impact of expression of the cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , on disease free survival and progression free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aqueous partition of bee venom showed strong dose dependent inhibitory effects on COX 2 activity ( IC 50 = 13 . 1 microg / mL ) , but did not inhibit COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Additionally , it selectively downregulated COX 2 , but not COX 1 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Resting FLS expressed mRNA encoding both COX 1 and COX 2 , but only COX 1 was present at the protein level . ^^^ Upon stimulation with IL 1beta , elevation of COX 2 , but not COX 1 , mRNA and protein preceded the enhancement of PGE ( 2 ) synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several reports have confirmed COX independent effects of celecoxib , at relatively high concentrations ( 50 microM ) , where apoptosis is stimulated in cells that lack both COX 1 and COX 2 [ 126 ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The gastric mucosal gene expressions of PPARgamma , interleukin 1beta ( IL 1beta ) , tumour necrosis factor alpha ( TNF alpha ) , leptin , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) were examined by RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This action is presumed to result from nonselective inhibition of both constitutive and inducible forms of prostaglandin H synthases , also known as the cyclooxygenase enzymes ( i . e . , COX 1 amd COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pretreatment of EC with TcdB 10643 prevented lipopolysaccharide ( LPS ) or tumor necrosis factor alpha ( TNFalpha ) related COX 2 expression but had no effect on COX 1 protein levels . ^^^ Therefore , RhoA / Rac1 / Cdc42 contribute to NF kappaB dependent LPS and TNFalpha induced expression of PGHS 2 in EC but had no effect on the activity of expressed COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A majority of animal studies provide strong evidence that prevention of intestinal tumors is more efficiently accomplished by COX 2 selective inhibition rather than by COX 1 suppression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 2 selective agents , the coxibs , which inhibit prostanoid biosynthesis at inflammatory sites , but not the endogenous protective prostanoids in the gut formed by COX 1 , have proved so far to be a successful therapeutic approach to reducing NSAIDs GI damage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , the specific roles of COX 1 , the constitutive form of cyclooxygenase , and COX 2 in LPS induced fever are not well understood . ^^^ We injected LPS i . v . in combination with either a highly selective COX 1 ( SC 560 ) or COX 2 ( SC 236 ) inhibitor to determine the effects of each drug on the subsequent fever response and on the pattern of expression of Fos protein in the brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two forms of COX , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : The levels of urinary protein and TXB ( 2 ) as well as cortical COX 2 expression in SNX group were significantly increased while COX 1 expression remained undisturbed in comparison with those in sham group . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the effects of inhibitors of COX 1 or COX 2 on myometrial prostaglandin synthesis and on spontaneous contractions in human myometrium . ^^^ METHODS : Cultured myometrial cells were incubated with SC 58560 ( COX 1 selective inhibitor ) or SC 58236 ( COX 2 selective inhibitor ) , and the production of prostaglandins determined by ELISA . ^^^ Spontaneously contracting strips of isolated gravid human lower segment myometrium were incubated with SC 58236 , meloxicam , DFU , or nimesulide ( COX 2 selective inhibitors ) , with SC 58560 ( COX 1 selective inhibitor ) or indomethacin ( non selective inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated expression of COX 1 and COX 2 in cell lines and tumors from ovarian carcinomas . ^^^ There was no significant correlation between COX 2 or COX 1 expression and other clinicopathological markers . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study COX 2 was detected in three of six PaCa cell lines while COX 1 was identified in all cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Differential COX inhibition studies revealed that purinergic stimulated release of PGE 2 was more sensitive to a COX 1 specific inhibitor ( valeroyl salicylate ) than a COX 2 specific inhibitor ( NS 398 ) . ^^^ Thus purinergic stimulation resulted in significantly more release of PGE 2 in the presence of COX 2 inhibitor than COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : This study examines the relationship between expression of COX 1 , COX 2 , and vascular endothelial growth factor ( VEGF ) , and their association with clinicopathological features in primary tumor and metastatic lymph node specimens from cervical cancer patients . ^^^ Immunohistochemical analysis was performed with antibodies to COX 1 , COX 2 , and VEGF . ^^^ RESULTS : VEGF expression was strongly correlated with expression of COX 1 ( P = 0 . 03 ) and not COX 2 ( P = 0 . 12 ) in primary tumor and metastatic lymph nodes . ^^^ CONCLUSION : COX 2 expression is associated with lymph node metastasis and possibly parametrial invasion , but expression of COX 1 and VEGF is not associated with clinicopathological features . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Specific COX 2 but not COX 1 inhibitors prevented intravitreal neovascularization , whereas prostaglandin E 2 , mainly via its prostaglandin E receptor 3 ( EP 3 ) , exacerbated neovascularization . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) genes ( COX 1 and COX 2 ) are known to be involved in the carcinogenesis of human and some animal urothelial tumors . ^^^ The aim of the present study was to investigate COX 1 and COX 2 expression by immunohistochemical methods in 20 bovine urothelial carcinomas collected at public slaughterhouses from cows that had been suffering from chronic enzootic hematuria . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Transfection analyses of the native or chimeric cPLA ( 2 ) alpha in combination with COX 1 or COX 2 revealed that , even though the arachidonate releasing capacities of native and mutant cPLA ( 2 ) alpha were comparable , prostaglandin production by mutant cPLA ( 2 ) alpha was markedly impaired as compared with that by native cPLA ( 2 ) alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Also the significance of prostaglandins ( PG ) generated by constitutive and inducible cyclooxygenase ( COX 1 and COX 2 ) in the stimulation of hypothalamic pituitary adrenal ( HPA ) axis by AVP under basal and crowding stress conditions was investigated . ^^^ Indomethacin ( 2 . 0 mg / kg i . p . ) , a non selective COX inhibitor , piroxicam ( 0 . 2 , 2 . 0 , and 5 . 0 mg / kg ) , a more potent COX 1 than COX 2 inhibitor , and compound NS 398 ( 0 . 2 and 2 . 0 mg / kg ) a selective COX 2 inhibitor , were administered i . p . 15 min prior to AVP ( 5 . 0 microg / kg i . p . ) to control or crowded rats . ^^^ Therefore , PG generated by COX 1 or COX 2 do not participate to a significant extent in the HPA stimulation by AVP during crowding stress . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , diclofenac , and SC 560 ( a selective COX 1 inhibitor ) , but not rofecoxib ( a selective COX 2 inhibitor ) , significantly inhibited lesion formation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In several cell lines , mPGES 2 promoted PGE 2 production via both COX 1 and COX 2 in the immediate and delayed responses with modest COX 2 preference . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 protein and its product PGE 2 were also increased , whereas COX 1 expression was unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PMA induced COX 1 expression in U 937 cells whereas LPS induced COX 2 expression in macrophages . ^^^ Although TNFalpha and M CSF induced a significant amount of AA release in both cell models , they failed to induce a comparable production of PGE 2 since they were unable to induce the coordinate expression of the downstream key enzymes , COX 1 or COX 2 . ^^^ In addition , PMA stimulates PGE 2 production via up regulation of COX 1 , and likely COX 2 , expression in U 937 cells whereas LPS stimulates PGE 2 production via induction of COX 2 expression in macrophages . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 1 is constitutively expressed in most tissues and may be involved in cellular homeostasis , whereas the COX 2 is an inducible enzyme that may play an important role in inflammation and mitogenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These genes include annexin 1 , annexin 2 , COX 2 , cyclooxygenase 1 ( COX 1 ) and cytosolic phospholipase A ( 2 ) ( cPLA ( 2 ) ) , 5 lipoxygenase ( 5 LOX ) , 5 lipoxygenase activating protein ( FLAP ) and 12 lipoxygenase ( 12 LOX ) ( not included in the array data ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 1 produces prostaglandin mediators for physiological reactions , COX 2 is overexpressed in acute pancreatitis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 is highly regulated and induced by inflammation while COX 1 is considered primarily a housekeeping form . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : In long term outcomes studies , cyclooxygenase COX 2 specific inhibitors spare COX 1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti inflammatory drugs ( NSAIDs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Hence , the developmental toxicity seen in rats after exposure to aspirin may be due to the irreversible inhibition of COX 1 and / or COX 2 . ^^^ Such a finding is consistent with the concept that reversible inhibition of COX 1 and / or COX 2 by other NSAIDs would produce weaker developmental toxicity signals than aspirin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Traditional nonsteroidal anti inflammatory drugs ( NSAIDs ) such as diclofenac , ibuprofen , naproxen , and related agents are nonselective inhibitors of both cyclooxygenase 1 ( COX 1 ) and COX 2 , which catalyze prostaglandin synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Other rats received intrathecally the COX 1 preferring inhibitor , ketorolac , the specific COX 1 inhibitor , SC 560 , the COX 2 inhibitor , NS 398 or vehicle 1 day after surgery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 expression was induced in macrophages ( Mphis ) , whereas COX 2 was induced in neutrophils . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Assessment of the relative contribution of COX 1 and COX 2 isoforms to ischemia induced oxidative damage and neurodegeneration following transient global cerebral ischemia . ^^^ We investigated the relative contribution of COX 1 and / or COX 2 to oxidative damage , prostaglandin E 2 ( PGE 2 ) production and hippocampal CA 1 neuronal loss in a model of 5 min transient global cerebral ischemia in gerbils . ^^^ The late increase in PGE 2 levels ( 24 h ) was more potently reduced by the highly selective COX 2 inhibitor rofecoxib ( 20 mg / kg ) relative to the COX 1 inhibitor valeryl salicylate ( 20 mg / kg ) . ^^^ Interestingly , either selective inhibition of COX 2 with rofecoxib or inhibition of COX 1 with valeryl salicylate significantly increased the number of healthy neurons in the hippocampal CA 1 sector even when the treatment began 6 h after ischemia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discoveries that cyclooxygenase COX 2 is an inducible form of COX involved in inflammation and COX 1 is the major isoform responsible for the production of prostaglandins have provided a reasonable basis for the development of specific COX 2 inhibitors as a new class of anti inflammatory agents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although SC 560 , a selective COX 1 inhibitor , did not affect steroidogenesis , the COX 2 inhibitor NS 398 significantly enhanced Bt ( 2 ) cAMP stimulated StAR protein expression and steroid production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Aspirin , an NSAID that irreversibly inhibits cyclooxygenase 1 ( COX 1 ) and COX 2 , induces DH , VSD , and MD when administered as one dose during the sensitive periods of development in rats . ^^^ To evaluate whether the dysmorphogenesis observed after maternal NSAID exposure correlates with COX 1 or COX 2 inhibition , a series of compounds with different capacities to inhibit COX 1 and COX 2 were administered to pregnant rats and rabbits during the sensitive period for heart development and midline closure . ^^^ METHODS : The compounds selected , ranked from the most COX 2 selective to the most COX 1 selective based onCOX inhibition in a human whole blood assay , were CJ 19 , 209 , meloxicam , diclofenac , diflunisal , ibuprofen , and ketorolac . ^^^ In general the induction of developmental defects was associated with compounds that selectively inhibit COX 1 or have a high ratio of COX 1 to COX 2 inhibition . ^^^ CONCLUSIONS : Inhibition of COX 1 may be involved in the disruption of heart development , whereas the selective inhibition of COX 2 ( as assessed with CJ 19 , 209 ) appears to have no effect on heart development and midline closure in rats and rabbits . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The new compounds were evaluated both in vitro ( COX 1 and COX 2 inhibition in human whole blood ) and in vivo ( carrageenan induced paw edema , air pouch , and hyperalgesia tests ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The William Harvey Research Conference held in Porto , Portugal , October 23 , 2000 , reviewed the history of the use of NSAIDs and discussed the pathological and physiological significance of the COX 2 enzyme while covering topics ranging from assays to measure the COX 2 : COX 1 ratio , the structural basis for COX 2 selectivity , potential mechanisms of NSAID induced gastrointestinal toxicity , preclinical studies , effects of COX 2 inhibitors on the kidney and vascular systems , to the latest clinical results , as well as the potential implication of COX 2 in cancer and Alzheimer ' s disease . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
HMCM induced a transient increase of COX 2 mRNA expression at 1 and 3 h without affecting the COX 1 mRNA level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this review we will focus on the role , expression and regulation of COX 1 and COX 2 in AD brain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The physiology and pathophysiology of both COX isoforms ( COX 1 , COX 2 ) are also discussed . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biological effects induced by aspirin and indomethacin on T98G cells , in which the expression of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) were confirmed by RT PCR and immunostaining , were investigated by studying cell proliferation and apoptosis assays . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Accordingly , we analyzed 108 colorectal adenomas for COX 1 and COX 2 transcription in archival formalin fixed , paraffin embedded tissue using by real time PCR and normalized to beta actin . ^^^ Neither COX 1 nor COX 2 mRNA expression differed with regard to age or gender of the subject . ^^^ Additionally , there was not a significant difference in either COX 1 or COX 2 based on the degree of dysplasia Therefore , if COX 2 inhibitors work through a COX 2 mechanism , these agents may have differential effects on colorectal adenomas that are distal and larger . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We compared the mechanical properties of bones from mice lacking either a functional cycloxygenase 1 ( C57BL6 / DBA COX 1 / ; n = 9 ) or COX 2 ( C57BL6 / DBA COX 2 / ; n = 9 ) gene and wild type mice ( C57BL6 / DBA ; n = 10 ) . ^^^ Finally , the bone matrix properties of COX 1 / mice , COX 2 / mice and their heterozygous littermates were similar to those of C57BL6 / DBA wild type mice . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , the heat treated leaf extract exhibited stronger inhibitory effects than the effects of the sun dried leaf extract at low concentrations in the studies of Concanavalin A induced histamine release , 5 lipoxygenase inhibition , and also inhibition of cyclooxygenases ( COX 1 and COX 2 ) , whereas K3G showed weak inhibitory effects on Concanavalin A induced histamine release , 5 lipoxygenase , and COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases , COX 1 and COX 2 , are two key enzymes in the conversion of arachidonic acid to PGE 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 1 , COX 2 , and PGDH gene expression was determined by semiquantitative reverse transcription polymerase chain reaction . ^^^ The HKE exposure up regulated expression of COX 2 , but not of COX 1 , in maternal tissues in both mouse strains . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Amounts of mRNAs for COX 2 and cPLA 2 , but not for COX 1 , were enhanced by LPS in PMNLs and MNLs . ^^^ Macrolide antibiotics inhibited PGE 2 synthesis in human leukocytes by suppressing cPLA 2 , COX 1 , and COX 2 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We compared small intestinal function and morphology in untreated wild type , COX 1 and COX 2 deficient mice and the effect of indomethacin , selective COX 1 ( SC 560 ) , and COX 2 ( celecoxib ) inhibition . ^^^ Selective inhibition of COX 1 decreased intestinal PGE ( 2 ) levels in COX 2 ( + / + ) and COX 2 ( / ) animals by 95 % 97 % , but caused only small bowel ulcers in the latter group . ^^^ Dual inhibition of COX 1 and COX 2 in wild type animals resulted in similar small bowel damage . ^^^ CONCLUSIONS : COX 1 deficiency or inhibition and short term COX 2 inhibition are compatible with normal small intestinal integrity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The experiments were performed in a liquid aqueous model system using COX 1 as well as by the in vitro feeding of VD ( 3 ) differentiated and LPS stimulated promyelocytic HL 60 cells using the cell ' s own COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These responses were attenuated by selective COX 2 inhibitors and a selective COX 1 inhibitor , whereas responses to exogenous prostanoids were not altered . ^^^ CONCLUSIONS : The results of these experiments suggest that arachidonic acid is converted into vasoactive prostanoids by the COX 2 and COX 1 pathway in the pulmonary and peripheral vascular beds in the rat and that TXA 2 is a major prostanoid formed in the normal rat lung . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although COX 1 is constitutively expressed in a wide range of tissues , COX 2 is cytokine inducible . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of the inducible cyclooxygenase enzyme ( COX 2 ) and development of some highly selective inhibitors ( which spare the constitutive COX 1 activity ) has renewed excitement for modulating tumor prostaglandins as a method of specific radiosensitization of tumors , while sparing normal tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The protein expression of COX 1 or COX 2 was unchanged by treatment with rofecoxib or sulindac because these agents inhibit enzyme activity and prostaglandin product formation rather than transcription of the COX genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Meloxicam is a nonsteroidal anti inflammatory drug ( NSAID ) that preferentially inhibits COX 2 more than cyclooxygenase 1 ( COX 1 ) , especially at low doses , thereby offering advantages over traditional nonselective NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed that both COX 1 and COX 2 were significantly increased in the sciatic nerve at the peak stage of EAN and declined during the recovery stage . ^^^ Vascular endothelial cells in normal sciatic nerves immunostained for both COX 1 and COX 2 . ^^^ COX 1 was mainly detected in macrophages , and not in other cell types , while COX 2 was detected in Schwann cells and axons as well as inflammatory macrophages in EAN lesions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Local PGE ( 2 ) formation is sustained by cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) , a possible exception being the mouse in which COX 1 , or both COXs , are reportedly absent . ^^^ COX 1 and COX 2 were detected in smooth muscle cells by immunogold electronmicroscopy , both being located primarily in the perinuclear region . ^^^ COX 1 and , far more frequently , COX 2 were colocalised with mPGES , while neither COX appeared to be colocalized with cPGES . 3 . ^^^ We conclude that the mouse ductus has a complete system for PGE ( 2 ) synthesis comprising both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Upon induction of differentiation , expression of cyclooxygenase 2 ( COX 2 ) was transiently induced and then declined , whereas COX 1 expression declined gradually as differentiation progressed . ^^^ Treatment with arachidonic acid led to sustained expression of COX 1 and COX 2 . ^^^ Unexpectedly , we observed that selective COX 1 or COX 2 inhibitors rescued adipocyte differentiation in the presence of arachidonic acid as effectively as did the nonselective COX inhibitor indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several modes of inhibitor binding in the COX active site have been described including ion pairing of carboxylic acid containing inhibitors with Arg 120 of COX 1 and COX 2 and insertion of arylsulfonamides and sulfones into the COX 2 side pocket . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effect of WEDC on the activity of COX 1 and COX 2 in vitro and its ulcerogenic capacity in vivo were also investigated . ^^^ In the evaluation of COX activity , we observed that WEDC was able to selectively inhibit COX 2 but not COX 1 activity in COS 7 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A selective COX 1 inhibitor , SC 560 , selective COX 2 inhibitors , NS 398 and celecoxib , and indomethacin were administered 30 min before ischemia . ^^^ These results suggest that COX 1 and COX 2 contribute to I / R induced hepatic microvascular and hepatocellular injury partly through TNF alpha production , and that TXs derived from COX are partly responsible for I / R induced liver injury . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The additional key to the marketing success is the purity and simplicity of the message that is , COX 1 inhibition causes the gastrointestinal side effects of NSAIDs ( COX 1 dogma ) while COX 2 blocking confers the therapeutic benefits ( COX 2 dogma ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 are induced in testicular cancer , and these results indicate that both COX 1 and COX 2 are essential for the growth of TC cells . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To determine the mechanism of action of E 2 , COX 1 and COX 2 were measured by Western blotting and OTR number was measured by saturation analysis . ^^^ OT increased COX 2 ( P < 0 . 05 ) , but there was no significant effect of E 2 on the expression of either COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 play critical roles in intestinal polyp formation , whereas COX 2 is also expressed in cancers of a variety of organs . ^^^ Here we show colocalization of COX 1 , COX 2 and mPGES in the intestinal polyp stromal fibroblasts of Apc ( Delta 716 ) mice , a model for familial adenomatous polyposis . ^^^ Contrary to COX 2 that was induced only in polyps > 1 mm in diameter , COX 1 was found in polyps of any size . ^^^ In polyps > 1 mm , not only COX 2 but also mPGES was induced in the stromal fibroblasts where COX 1 had already been expressed . ^^^ Although polyp number and size were markedly reduced in COX 1 ( / ) or COX 2 ( / ) compound mutant Apc mice , both COX 2 and mPGES were induced in the COX 1 ( / ) polyps , whereas COX 1 was expressed in the COX 2 ( / ) polyps . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
End points included assessment of COX 1 and COX 2 gene expression by reverse transcription polymerase chain reaction ( RT PCR ) ; COX 1 , COX 2 , p 38 , and p42 / 44 protein by Western analysis ; and measurement of PGE 2 and 6 keto PGF1alpha releases by GC / MS . ^^^ Both GSE and NAC resulted in significant exacerbation of the LPS stimulated increase in COX 2 gene and protein expression and prostaglandin release , and suppressed the LPS induced decrease in COX 1 . ^^^ Inhibition of either p 38 or p42 / 44 MAPKs suppressed LPS stimulated COX 2 gene and protein expression , and prostaglandin release ( P < 0 . 05 ) but had little effect on COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Overexpression of FLAP did not alter Bcl xL protein expression , but did decrease Bax protein and somewhat increased COX 1 and COX 2 mRNA levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) enzymes catalyze the synthesis of prostaglandins and exist as two isoforms , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The putative chemopreventive actions include the inhibition of inflammatory cascades and / or reactions involved in cell growth and proliferation , such as cyclo oxygenase ( COX 1 and COX 2 ) , which regulate cell proliferation through the formation of prostaglandins ; lipoxygenase ; nuclear factor kappaB ( NFkappaB ) , responsible for the subsequent expression of pro inflammatory molecules ; MAP kinases and Bcl 2 , as well as the activation of apoptotic processes , such as the stimulation of intestinal sphingomyelinase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase one ( COX 1 ) and COX 2 are rate limiting enzymes in PGF synthesis , and COX 2 is the major form expressed in ovine endometrium . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mice infected with H . pylori were given selective COX 1 inhibitor SC 560 ( 10 mg / kg ) , selective COX 2 inhibitor NS 398 ( 10 mg / kg ) , or nonselective COX inhibitor indomethacin ( 2 mg / kg ) with or without 16 , 16 dimethyl PGE 2 for 1 wk . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Transient transfections with COX 2 promoter luciferase construct and various inhibitors of mitogen activated protein kinases ( MAPK ) , such as protein kinase C ( PKC ) inhibitor GF203190X , p 38 ( MAPK ) inhibitor SB 203109 , and extracellular regulated kinases 1 and 2 inhibitor PD 98509 showed that C . albicans up regulates selectively COX 2 , but not COX 1 , through p 38 ( MAPK ) and PKC pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These findings suggests that ( 1 ) aspirin and NCX 4016 trigger ATL formation in humans , ( 2 ) celecoxib inhibits ATL formation and exacerbates the mucosal injury caused by low doses of aspirin , and ( 3 ) the NO donating moiety of NCX 4016 protects the gastric mucosa even in the presence of suppression of COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To address this question pharmacologically , we tested the effects of selective inhibitors of COX 1 and COX 2 on paw edema and the formation of arachidonic acid metabolites in the inflamed paws immunized with type 2 collagen ( CII ) . ^^^ These results suggest that COX 2 , but not COX 1 , contributes to the edema and the formation of PGE ( 2 ) and TXB ( 2 ) in mouse CIA model . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Protein expressions of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) and cytosolic phospholipase A 2 ( cPLA 2 ) over the ulcer margin were evaluated , and the mucosal prostaglandin E 2 ( PGE 2 ) level was also determined . ^^^ These were associated with a significant decrease of COX 2 expression and PGE 2 level but not COX 1 at the ulcer margin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Biopsy samples were taken for the measurement of prostaglandin ( PG ) E ( 2 ) by radioimmunoassay and mucosal expression of constitutive and inducible nitric oxide synthase ( cNOS and iNOS ) , constitutive ( COX 1 ) and inducible cyclooxygenase ( COX 2 ) , heat shock protein 70 ( HSP 70 ) mRNA and protein were analyzed by RT PCR and Western blot . ^^^ The signals for cNOS , COX 1 and HSP 70 mRNA were detected by RT PCR in the vehicle treated gastric mucosa , whereas gene and protein expression of iNOS , COX 2 and HSP 70 mRNA were significantly increased only in rats treated with 1 or 5 applications of HP LPS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : In short term in vitro assays , neither aceclofenac nor 4 ' hydroxy aceclofenac affected COX 1 or COX 2 , whereas diclofenac and 4 ' hydroxy diclofenac inhibited both isoforms . ^^^ Maximal plasma concentrations of diclofenac after oral administration of aceclofenac ( 0 . 39 micromol / L ) or diclofenac ( 1 . 28 micromol / L ) were sufficient for a greater than 97 % inhibition of COX 2 ( 50 % inhibitory concentration , 0 . 024 micromol / L ) and a 46 % ( aceclofenac treatment ) or 82 % inhibition ( diclofenac treatment ) of COX 1 ( 50 % inhibitory concentration , 0 . 43 micromol / L ) . ^^^ Although 100 mg aceclofenac yielded diclofenac concentrations substantially lower than 75 mg diclofenac , these were sufficient for a sustained block of COX 2 but caused a minor and shorter inhibition of COX 1 than 75 mg diclofenac . ^^^ In conclusion , both COX 1 sparing and COX 2 inhibitory actions of aceclofenac may rest in its limited but sustained biotransformation to diclofenac . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Given i . v . , the sPLA 2 inhibitor was more effective than either the COX 1 or COX 2 inhibitors in preventing rat I / R injury . ( 6 ) These results indicate that a potent new inhibitor of sPLA 2 ( group IIa ) protects the rat small intestine from I / R injury after oral or intravenous administration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of ex vivo arachidonic acid ( AA ) induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase ( COX ) inhibitors since platelets express COX 1 but not COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Endothelial dysfunction was evaluated by performing concentration effect curves to acetylcholine after precontracting the liver with methoxamine in groups of control and CCl ( 4 ) cirrhotic rat livers preincubated either with vehicle , indomethacin , the COX 1 selective inhibitor , SC 560 , the COX 2 selective inhibitor , SC 236 , the thromboxane A ( 2 ) receptor antagonist , SQ 29 , 548 or the nitric oxide ( NO ) synthase inhibitor N ( G ) nitro L arginine . ^^^ COX 1 inhibition and TXA ( 2 ) blockade , but not COX 2 inhibition , also corrected endothelial dysfunction . ^^^ Indomethacin and COX 1 inhibition , but not COX 2 or NO inhibition , prevented the increased production of TXA ( 2 ) . ^^^ This is mainly mediated by COX 1 , but not by COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although indomethacin is currently the most common non steroidal anti inflammatory drug ( NSAID ) used in the treatment of preterm labour , it was hoped that COX 2 selective drugs , used as tocolytics , would target COX 2 activity and potentially spare COX 1 specific fetal side effects . ^^^ It is unclear whether this is due to COX 2 dependent side effects , or due to accumulation of drug in the fetal circulation leading to levels that would cause COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Current NSAIDs inhibit both COX 1 and COX 2 , although the clinical benefit of NSAIDs appears to be associated with inhibition of COX 2 activity . ^^^ Current data would suggest that by inhibiting COX 2 action , these agents may have efficacy similar to that of standard NSAIDs and that by not inhibiting COX 1 activity , they may have less toxicity than standard NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The reason for this was resolved by the discovery that prostaglandins at sites of tissue damage were synthesized by an inducible COX ( COX 2 ) formed by a gene distinct from that producing the constitutive enzyme ( COX 1 ) , responsible for the formation of prostaglandins that serve an essential physiological function . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Structure of COX 1 and COX 2 enzymes and their interaction with inhibitors . ^^^ Nevertheless , there are very important biological differences between COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Measurement of differential inhibition of COX 1 and COX 2 and the pharmacology of selective inhibitors . ^^^ Since the discovery of a second isoenzyme of cyclooxygenase ( COX ) 2 , it has been hypothesized that the antiinflammatory effects of non steroidal antiinflammatory drugs ( NSAIDs ) are dependent on their inhibition of COX 2 , whereas inhibition of constitutive COX 1 is responsible for their gastric and renal side effects as well as for inhibition of platelet activation . ^^^ Consequently , a large number of in vitro assays have been developed to characterize the COX 1 and COX 2 inhibitory activities of NSAIDs in order to look for compounds with preferential inhibition of COX 2 . ^^^ These important variables include the source of enzymes COX 1 and COX 2 ( human or animal ) ; the cell system used ( intact normal cells or transfected cell lines ) ; the method of enzyme preparation ( purified enzymes , microsomal or whole cell assays ) ; the COX 2 inducing agent ; the source of arachidonic acid and its concentration ; the incubation time with drug , inducing agent or arachidonic acid ; and the protein concentration in the medium . ^^^ Depending on the test system employed for defining the IC ( 50 ) for COX 1 and COX 2 inhibition , the resultant ratio between these activities may lead to divergent and confusing comparisons . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of COX , the constitutive enzyme COX 1 , which is responsible for the production of PGs with general housekeeping functions such as maintenance of renal perfusion and a protective effect on the gastric mucosa against ulceration ; and the inducible enzyme COX 2 , which is responsible for the production of proinflammatory PGs . ^^^ The crucial issue is that patients who benefit most from NSAIDs are those who will be most likely to have side effects from the nonselective COX 1 and COX 2 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ( SC 560 ) ( a selective COX 1 inhibitor ) , or rofecoxib ( a selective COX 2 inhibitor ) was given intraduodenally 30 min before the TC treatment . ^^^ These results suggested that COX 1 but not COX 2 is a key enzyme for regulating the functional alterations of the stomach and for maintaining the mucosal integrity after barrier disruption . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All compounds ( 7 11 ) were tested in vitro towards COX 2 , and compounds 7 9 towards COX 1 , by measuring prostaglandin E 2 ( PGE ( 2 ) ) production in activated J774 . 2 macrophages and U 937 cell lines , respectively . ^^^ While all new compounds were found to possess little or no activity on the COX 2 isoenzyme , some of these ( 7a 7d , 8a , 8d , 9e and 9f ) appeared to possess an appreciable activity on COX 1 , with % inhibition values at a concentration of 1 microM ranging from 30 % of 8a to 76 % of 9e . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , docking studies were carried out on the most significative compounds to evaluate their interaction mode at the active site of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compounds 1 4 showed 3 . 32 , 45 . 32 , 46 . 15 , and 3 . 15 % of prostaglandin H endoperoxide synthase 1 ( COX 1 ) inhibitory activity and 52 . 69 , 68 . 41 , 64 . 39 and 0 % prostaglandin H endoperoxide synthase 2 ( COX 2 ) inhibitory activity , respectively at 100 mg mL ( 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inductions of COX 2 mRNA and protein by UV in aged skin were higher than those in the young skin , whereas COX 1 mRNA expression remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the isozyme activities of COX 1 and COX 2 in TCC cells and correlate with cellular differentiation and tumor behavior . ^^^ MATERIAL AND METHODS : Various TCC cell lines were characterized through several aspects : ( 1 ) . to measure the content and the mRNA amount of COX 1 and COX 2 , ( 2 ) . to characterize the proteins of COX 1 and COX 2 by Western immunoblotting , ( 3 ) . to measure the production of prostaglandin E 2 and thromboxane B 2 in culture media , and ( 4 ) . to correlate these parameters with tumor differentiation and invasiveness . ^^^ Tumors with lower grade differentiation and less invasiveness had significantly higher content of COX 1 and COX 2 than those tumors with higher grade differentiation and more invasive behavior ( p < 0 . 01 ) . ^^^ CONCLUSIONS : The expression of COX 1 and COX 2 is a common phenomenon in TCC cells and closely related to cellular differentiation and tumor invasiveness . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 mRNA and protein were constitutively expressed , whereas COX 2 was highly modulated in uteroplacental tissues throughout pregnancy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We examined the expression of the 2 COX isoforms COX 1 and COX 2 in different regions of the kidney in rats subjected to UUO . ^^^ COX 1 and COX 2 expression in the cortex and medulla were examined by Western blot analysis and immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Application of the RP trees to a validation set of Merck cyclooxygenase inhibitors shows good consistency with the COX 1 and COX 2 activity data , albeit moderate consistency with the selectivity data . ^^^ Compared to the independent RP models ( obtained by considering each activity separately ) , the PUMP RP decision trees provide easier identification and interpretation of those descriptors that are common to both COX 1 and COX 2 activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX enzyme family consists of the classic COX 1 and a second enzyme , COX 2 , which is induced by various stimuli , such as mitogens and cytokines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : Cyclo oxygenase ( COX ) exists in two isoforms , COX 1 and COX 2 . ^^^ COX 1 is responsible for homeostatic functions , whereas COX 2 is inducible and responsible for the inflammatory effects of prostaglandins . ^^^ COX 1 and COX 2 activities in whole blood were estimated by serum thromboxane B 2 ( TxB 2 ) and endotoxin induced PGE 2 concentrations respectively . ^^^ Synovial tissue COX 1 and COX 2 mRNA and protein expression were studied by reverse transcriptase polymerase chain reaction and immunohistochemistry respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The study suggests that expression of COXs may influence A beta peptide generation through mechanisms that involve PG E 2 mediated potentiation of gamma secretase activity , further supporting a role for COX 2 and COX 1 in Alzheimer ' s disease neuropathology . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both isoenzymes ( COX 1 and COX 2 ) were detected in cultured cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The increases in potency of ibuprofen , flufenamic acid , isoxicam and niflumic acid towards Cox 2 and ibuprofen towards Cox 1 were accompanied by a change from time independent to time dependent inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : COX 1 and COX 2 expression in bronchiolar epithelial cells was significantly lower in IPF and sarcoidosis than in controls . ^^^ CONCLUSIONS : These studies confirm COX 2 loss in bronchial epithelial cells but not macrophages in IPF , and show for the first time reduced constitutive COX 1 expression in epithelial cells and macrophages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
They are produced by two different isoforms of the cyclooxygenase ( COX ) enzyme , namely COX 1 and COX 2 . ^^^ Therefore , we investigated the expression of COX 1 and COX 2 in the spinal cord of seven human sporadic ALS patients by means of immunohistochemistry . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Considering that the induction of COX 1 and COX 2 are inhibited by ketoprofen , and that these enzymes are located in the stromal compartment of the CAM , we propose that its antiangiogenic effect may occur via inhibition of the two COX isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We first confirmed that incubation of HMC with 30 mmol / l glucose significantly increased COX 2 mRNA but not COX 1 mRNA , compared with 5 . 6 mmol / l glucose . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , human tendon fibroblasts had increased expression of both COX 1 and COX 2 for all three applied stretching magnitudes , with the exception of COX 1 at 4 % cyclic stretching . ^^^ As PGE ( 2 ) is a known inflammatory mediator of tendinitis , the contribution of COX 1 and COX 2 to PGE ( 2 ) production and their roles in tendon inflammation are clearly indicated . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inhibition of COX 1 , but not COX 2 , was shown to precipitate post challenge symptoms precipitated by aspirin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study we describe the synthesis of two novel 4 phenyl and 4 ( 2 chlorophenyl ) 6 ( 5 chloro 2 oxo 3H benzoxazol 7 yl ) 3 ( 2H ) pyridazinone derivatives ( compounds 8a and b ) and their testing as inhibitors of cyclooxygenases ( COX 1 and COX 2 ) . ^^^ Both compounds inhibited COX 1 ( by 59 % and 61 % for compounds 8a and 8b respectively and COX 2 ( by 37 % and 28 % for compounds 8a and 8b respectively ) at a concentration of 10 microM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synthesis and effects on the COX 1 and COX 2 activity in human whole blood ex vivo of derivatives containing the [ 1 ] benzothienol [ 3 , 2 d ] pyrimidin 4 one heterocyclic system . ^^^ Methyl and phenyl derivatives containing the [ 1 ] Benzothieno [ 3 , 2 d ] pyrimidin 4 one system have been synthesized and tested as inhibitors of COX 1 and COX 2 activities in human whole blood ( HWB ) ex vivo ; all compounds turned out to be weak inhibitors of COX 1 activity , as deduced from the TXB ( 2 ) ( thromboxane B ) generation ; the acid phenyl derivative 11 b was an interesting inhibitor of COX 2 activity , as deduced from the PGE ( 2 ) ( prostaglandine E ) generation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In 1991 , it was disclosed that COX exists in two distinct isozymes ( COX 1 and COX 2 ) , one of which , COX 2 , is primarily responsible for inflammation but apparently not for gastrointestinal integrity or platelet aggregation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By sparing COX 1 , COX 2 specific inhibitors provide effective anti inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual COX inhibitors ( traditional NSAIDs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the human stomach , COX 1 appears to be the predominant source of prostaglandins despite the fact that COX 2 is upregulated in H . pylori gastritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two COX enzymes , COX 1 and COX 2 . ^^^ The interest in the COX 2 enzyme is that specific inhibition of COX 2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors ( most NSAIDs ) or COX 1 inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Clinical implications of COX 1 and / or COX 2 inhibition for the distal gastrointestinal tract . ^^^ Data from different animal models of inflammatory bowel disease suggest that inhibition of both COX 1 and COX 2 derived prostaglandins affects the severity of the mucosal inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BAECs basally express COX 1 but not COX 2 , and COX 2 expression is only apparent after stimulation with phorbol 12 myristate acetate ( PMA ) . ^^^ There was no demonstrable effect of dsRNA COX 2 or PMA on COX 1 expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Most NSAIDs inhibit two isoforms of cyclooxygenases called Cox 1 and Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent studies have shown that selective COX 2 inhibitors ( rofecoxib and celecoxib ) , unlike COX 1 inhibitors , are very well tolerated by NSAID sensitive patients and do not elicit increased Cyst LTs production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While the COX 1 isoenzyme is mainly constitutive , the COX 2 form is inducible . ^^^ Because many of the unwanted effects of the NSAIDs have been associated with COX 1 inhibition , specific drugs with a high inhibitory activity toward the COX 2 isoenzyme have been developed in recent years . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of cyclooxygenase ( COX ) 2 has provided the rationale for the development of a new class of nonsteroidal antiinflammatory drugs ( NSAIDs ) , the selective COX 2 inhibitors ( denominated coxibs ) , with the aim of reducing the gastrointestinal ( GI ) toxicity associated with the administration of NSAIDs by virtue of COX 1 sparing . ^^^ Recently , other selective COX 2 inhibitors with different COX 1 / COX 2 selectivity and pharmacokinetic features have been developed , i . e . valdecoxib , parecoxib , etoricoxib and lumiracoxib . ^^^ The improved biochemical selectivity of valdecoxib vs celecoxib in vitro ( COX 1 / COX 2 ratio : 60 vs 30 , respectively ) may be clinically relevant leading to an improved GI safety . ^^^ Etoricoxib , showing only a slightly higher COX 2 selectivity than rofecoxib in vitro ( COX 1 / COX 2 ratio : 344 vs 272 , respectively ) , has been reported to cause a similar specific COX 2 inhibition ex vivo that should translate into comparable GI safety . ^^^ Lumiracoxib , the most selective COX 2 inhibitor in vitro ( COX 1 / COX 2 ratio : 400 ) , is the only acidic coxib . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exploring selectivity requirements for COX 2 versus COX 1 binding of 3 , 4 diaryloxazolones using E state index . ^^^ Considering the importance of developing selective COX 2 inhibitors , the present paper explores selectivity requirements for COX 2 versus COX 1 binding of 3 , 4 diaryloxazolones using electrotopological state ( E state ) index . ^^^ The study also shows the utility of E state index in developing statistically acceptable model having direct physicochemical significance : electron density distribution of different atoms of the oxazolone ring and attached two phenyl rings are important for the selective binding with COX 2 over COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Investigations have documented two isoforms , COX 1 and COX 2 , encoded by different genes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Molecules like nitro NSAIDs or tromethamine salt derivatives have been synthesized considering that both COX 1 and COX 2 are responsible for the synthesis of prostaglandins involved either in homeostatic functions or inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore the most potent compounds 2 g and 3 g from each series were screened in vitro for inhibition of both COX 2 and COX 1 catalysed prostaglandin biosynthesis ( radiochemical assay ) . ^^^ Compound 3 g was found to be more COX 2 selective , while compound 2 g was found to be equally COX 2 and COX 1 selective . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
S 180 cells implanted in ddy mice formed substantial tumors with extensive angiogenesis markedly suppressed by aspirin and COX 2 inhibitors NS 398 and JTE 522 , but not by mofezolac , an inhibitor of constitutive COX 1 . ^^^ S 180 tumor growth in the subcutaneous tissues was also suppressed by aspirin , COX 2 selective inhibitors , and the VEGF antibody , but not by the COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 1 and COX 2 . and of two cyclin dependent kinase inhibitors , p21Cip1 and p27Kip1 , was analysed by Western blotting and RT PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mucosal damage induced by the COX 1 inhibitor , the COX 2 inhibitors , and dexamethasone in L NAME or capsaicin treated rats was reversed by coadministration of 16 , 16 dimethyl prostaglandin E 2 ( 2 10 8 ng / kg ) . ^^^ The prostaglandins necessary for mucosal defense in the face of NO suppression , and afferent nerve ablation can be derived either from COX 1 or COX 2 . ^^^ Our findings suggest that not only COX 1 but also COX 2 has important functions in the maintenance of gastric integrity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biosynthesis of prostaglandins proceeds in the presence of fatty acid cycloxygenases ( COX 1 , COX 2 ) . ^^^ COX 1 is responsible for the synthesis of prostaglandins indispensable for normal homeostasis , while COX 2 regulates local expression of pro inflammatory prostaglandins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Swiss Webster mice were dosed with celecoxib and rofecoxib and challenged with CT in ligated small intestinal loops , and intestinal segments from mice deficient in COX 1 and COX 2 were challenged with CT . ^^^ Celecoxib and rofecoxib given at 160 micro g per mouse inhibited CT induced fluid accumulation by 48 % and 31 % , respectively , but there was no significant difference among cox 1 ( / ) and cox 2 ( / ) mice in response to CT compared to wild type controls . ^^^ CT elevated tissue levels of oxidized glutathione and lipid peroxides and elicited small intestinal tissue injury in two of five cox 1 ( / ) and four of five cox 2 ( / ) mice . ^^^ A role for COX 2 in CT ' s mechanism of action has previously been suggested by the effectiveness of COX 2 inhibitors in reducing CT induced fluid secretion , but CT challenge of COX 1 and COX 2 knockout mice did not corroborate the pharmacological data . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Until recently , the presence of only two isoforms COX 1 and COX 2 remained in question because the potent anti pyretic and analgesic effects of acetaminophen ( paracetamol , tylenol ben u ron ) could not be explained by either COX 1 or COX 2 blockades . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
More recently , selective COX 2 inhibitors ( ' coxibs ' ) were designed to inhibit the production of COX 2 dependent inflammatory prostanoids and to leave intact the cytoprotective COX 1 products . ^^^ Further elucidation of the relative roles of COX 1 and COX 2 generated prostanoids has enabled a greater understanding of the biology of these pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX has two isoforms , COX 1 and COX 2 . ^^^ For the purposes of this analysis , relative COX 1 selective NSAIDs were defined as having a ratio of COX 1 IC 50 to COX 2 IC 50 of > 1 in whole blood , and relative COX 2 selective NSAIDs were defined as having a ratio of COX 1 IC 50 to COX 2 IC 50 of < 1 in whole blood . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE 2 production in POBs from mice with only COX 1 gene expression was 1 / 40th of that in POBs from mice with both COX 1 and COX 2 gene expression . [ Ca2+ ] e increased alkaline phosphatase activity and osteocalcin mRNA , and this increase was blocked by inhibiting PGE 2 production . [ Ca2+ ] e stimulation of COX 2 promoter activity correlated with the induction of COX 2 mRNA expression . [ Ca2+ ] e induced rapid and transient phosphorylation of extracellular signal regulated kinase ( ERK ) in POBs , which peaked at 5 10 minutes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Molecular modeling studies , where 14i was docked in the active site of both COX 1 and COX 2 , reveals that the C 6 ethoxy substituent orients the pyran 2 one ring to position the SO ( 2 ) Me pharmacophore in the vicinity of the secondary pocket in COX 2 . ^^^ The absence of this COX 2 secondary pocket in the COX 1 binding site is due to the presence of the bulky Ile ( 523 ) in COX 1 such that access to the amino acid residues ( Ile ( 517 ) , Phe ( 518 ) , Gln ( 192 ) , and His ( 90 ) ) , which line the COX 2 secondary pocket with which the SO ( 2 ) Me pharmacophore could interact , is hindered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The constitutive isoform , COX 1 , supports the beneficial homeostatic functions , whereas the inducible isoform , COX 2 , becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas lipopolysaccharide ( LPS ) induced fever is attenuated in COX 2 gene deleted mice , suggesting that COX 2 is responsible for this type of fever , the COX 1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both selective COX 1 and COX 2 inhibitors aggravate gastric damage induced in rats by 2 deoxy D glucose . relation to gastric hypermotility and COX 2 expression . ^^^ CONCLUSION : These results suggest that potentiation by indomethacin of 2DG induced gastric lesions is related to inhibition of both COX 1 and COX 2 , and that 2DG up regulates COX 2 in the gastric mucosa , the event occurring in association with gastric hypermotility and contributing to suppression of later extension of the damage . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pretreatment with COX 1 and COX 3 inhibitors ( aspirin at a low dose of 1 mg kg ( 1 ) , SC 560 and acetaminophen , 0 . 3 3 mg kg ( 1 ) ) slightly augmented thrombolysis by ACE 1 , while COX 2 inhibitors ( nimesulide and coxibs at doses < 1 mg kg ( 1 ) and aspirin at a high dose of 50 mg kg ( 1 ) ) or a kinin B 2 receptor antagonist ( icatibant ) abolished it . ^^^ In aortas of Wistar rats , the transcripts of COX 2 and PGI S were overexpressed as compared to COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An incomplete suppression of platelet thromboxane ( TX ) A 2 biosynthesis has been assumed to participate in the phenomenon of aspirin resistance , as a consequence of the following possible mechanisms : ( 1 ) COX 2 expression in newly formed platelets ; ( 2 ) pharmacodynamic interactions between aspirin and coadministered nonsteroidal antiinflammatory drugs ( e . g . ibuprofen ) ; ( 3 ) expression of variant isoforms of COX 1 with reduced sensitivity to irreversible inactivation at Ser 529 . ^^^ Thus , in a subset of patients with unstable angina treated with low dose aspirin , to almost completely block platelet COX 1 activity , enhanced TXA 2 biosynthesis in vivo has been demonstrated , presumably through an increased generation of COX 2 dependent PGH 2 in plaque monocytes / macrophages or activated vascular cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 , but not COX 1 , protein levels markedly increased following hypoxia . ^^^ Use of the selective COX 2 inhibitor , NS 398 , indicated that COX activity in hypoxic corneas or cells is essentially that of COX 2 ; in control cells , both COX 1 and COX 2 contributed equally to the production of PGE 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effects of phenacetin and its metabolite p phenetidine on COX 1 and COX 2 activities and expression in vitro . ^^^ Collagen stimulated platelet thromboxane B 2 ( TxB 2 ) production and phorbol 12 myristate 13 acetate ( PMA ) induced neutrophil prostaglandin E 2 ( PGE 2 ) synthesis were used as indicators for COX 1 and COX 2 activity , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase ( COX ) isozymes have been characterized , COX 1 and COX 2 , that differ in terms of regulatory mechanisms of expression , tissue distribution , substrate specificity , preferential coupling to upstream and downstream enzymes , and susceptibility to inhibition by the extremely heterogeneous class of COX inhibitors . ^^^ Although the role of platelet COX 1 in acute coronary syndromes and ischemic stroke is firmly established through approximately 20 years of thromboxane metabolite measurements and aspirin trials , the role of COX 2 expression and inhibition in atherothrombosis is substantially uncertain , because the enzyme was first characterized in 1991 and selective COX 2 inhibitors became commercially available only in 1998 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that MSS 51 is required for expression of the mitochondrial reporter gene ARG 8 ( m ) when it is inserted at the COX 1 locus , but not when it is at COX 2 or COX 3 . ^^^ MSS 51 also acts on a target specified by the COX 1 coding region , since it was required to translate either COX 1 or COX 1 : : ARG 8 ( m ) coding sequences from an ectopic COX 2 locus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , the inhibition of COX enzyme by Ch 4 was selective for COX 2 over COX 1 . ^^^ Docking Ch 4 into the V523I mutant of COX 2 indicated that Ile 523 of COX 1 might contribute to the selectivity of COX 2 over COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These cytokines downregulated the expression of both COX 1 and COX 2 genes and decreased the production of PGE ( 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 2 expression increased several fold after lipopolysaccharide ( LPS ) challenge , COX 1 and COX 3 expression did not change significantly , suggesting that cells constitutively express COX 3 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 selective inhibitors provided greater protection than did COX 2 selective inhibitors or lipoxygenase inhibitors , suggesting that activation of COX 1 is required for amyloid beta 1 42 induced neurotoxicity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A new approach to the gastrointestinal complications of NSAIDs became feasible with the discovery of two isoforms of COX , COX 1 and COX 2 , with COX 1 expressed mainly in the gastrointestinal tract . ^^^ The development of NSAIDs that preferentially inhibit COX 2 offers the promise of relieving pain and inflammation without the side effects attendant to COX 1 blockade . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two known isoforms of the enzyme , Cox 1 , which is constitutively expressed and the inducible isoform , Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro COX 1 and COX 2 inhibition studies showed that 4 [ 5 ( 4 methylphenyl ) 3 trifluoromethyl 1H pyrazol 1 yl ] benzenesulfonyl azide ( 4 ) with a para SO ( 2 ) N ( 3 ) substituent was a selective COX 1 inhibitor . ^^^ In contrast , 3 [ 5 ( 4 methylphenyl ) 3 trifluoromethylpyrazol 1 yl ] benzenesulfonyl azide ( 8a ) having a meta SO ( 2 ) N ( 3 ) substituent ( COX 1 IC ( 50 ) > 100microM ; COX 2 IC ( 50 ) =5 . 16microM ; COX 2 selectivity index > 19 . 3 ) is a selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the expression of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in extra hepatic cholangiocarcinoma and the relationship between their expression and clinicopathological parameters . ^^^ METHODS : COX 1 and COX 2 were detected in 56 extra hepatic cholangiocarcinomas , including 31 matched tissues originating from non tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues , by immunohistochemistry strept avidin biotin complex using isozyme selective antibodies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we examined the inhibitory effects of 1 , 2 , 3 , 4 , 6 penta O galloyl beta D glucose ( PGG ) isolated from the root of Paeonia lactiflora Pall . on the COX 2 and iNOS activity in LPS activated Raw 264 . 7 cells , COX 1 in HEL cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of non specific COX inhibitors indomethacin , diclofenac , tolmetin , or aspirin ( n = 10 ) , or specific COX 1 or COX 2 inhibitors ( n = 3 ) on sperm mobility were measured ( Accudenz swim down test ) . ^^^ Cyclooxygenase inhibitors ( 0 . 001 to 10 mM ) decreased sperm mobility : indomethacin 15 to 100 % ; diclofenac 4 to 100 % ; tolmetin 27 to 74 % ; aspirin ( tested at 0 . 01 to 15 mM ) 22 to 42 % ; resveratrol ( COX 1 ) and NS 398 ( COX 2 ) , both tested at 0 . 1 to 10 mM , 38 to 98 % and 44 to 85 % , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , AngII and PMA induced PGI ( 2 ) production depended on protein synthesis and COX 2 but not COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of the COX 1 , but not the COX 2 pathway , attenuated H2O2 induced dilation similarly to indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 inhibitors did not alter , whereas a COX 1 inhibitor depressed , arachidonic acid induced platelet aggregation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gene induction was examined using 5 ' deletion constructs of the COX 1 and COX 2 promoters coupled with luciferase . ^^^ RESULTS : All H . pylori strains induced prostaglandin generation and expression of both COX 1 and COX 2 in HUVEC , although this was most pronounced with the highly toxigenic strain H . pylori 60190 . ^^^ CONCLUSIONS : H . pylori increased both COX 1 and COX 2 activity in vascular endothelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exposure of astrocytes to cytokines resulted in a time dependent increase in PGE 2 production that was marked by increased expression of secretory sPLA 2 and COX 2 , but not COX 1 and cytosolic cPLA 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : We investigated the expression of cyclooxygenase ( Cox 1 and Cox 2 ) in mammary tissues from patients with breast cancer . ^^^ RESULTS : The cancer cells showed very weak expression of Cox 1 , but strong expression of immunoreactive Cox 2 . ^^^ RT PCR analysis showed enhanced expression of Cox 2 , but not Cox 1 in breast cancer tissue , and faint expression of Cox 2 in benign tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whereas COX 1 is found in most tissues , COX 2 , with a few exceptions , is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions . ^^^ COX 1 and COX 2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT PCR , northern blot , and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The prostaglandin PGE 2 increases intracellular cAMP levels and stimulates estrogen biosynthesis , and previous studies in our laboratories have shown a strong linear association between aromatase ( CYP 19 ) expression and expression of the cyclooxygenases ( COX 1 and COX 2 ) in breast cancer specimens . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 appears to be the major enzyme involved in this axis because the specific COX 2 inhibitor NS 398 was twice as effective as the COX 1 inhibitor SC 560 in inhibiting the SRXS6c effect . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Previously we demonstrated that genetic deficiency of the cyclooxygenases ( COX 1 or COX 2 ) altered keratinocyte differentiation in mouse skin [ Tiano et . al . ( 2002 ) Cancer Res . 62 , 3395 3401 ] . ^^^ In this study , we show that topical application of SC 560 ( a COX 1 selective inhibitor ) or celecoxib ( COX 2 selective ) to TPA treated wild type skin caused fivefold increases in the number of basal keratinocytes expressing the early differentiation marker keratin 1 ( K 1 ) . ^^^ In contrast to skin , COX 2 not COX 1 was the major isoform expressed in cultured primary keratinocytes . ^^^ COX 1 was predominantly expressed in detached , differentiated cells , whereas COX 2 was found in the attached , proliferating cells . ^^^ High Ca++ medium induced K 1 and COX 1 in wild type keratinocytes but did not change COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs ( NSAIDs ) reduce prostaglandin synthesis by inhibiting cyclo oxygenase 1 ( COX 1 ) and / or cyclo oxygenase 2 ( COX 2 ) . ^^^ Different groups of NSAIDs , defined by their action on either COX 1 or COX 2 , have been developed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase isoforms , COX 1 and COX 2 , are involved in the biosynthesis of prostaglandin E 2 , a major prostaglandin involved in epidermal homeostasis and repair . ^^^ COX 2 inhibitors , which demonstrate significant in vivo selectivity relative to COX 1 , suppress both ultraviolet induced epidermal tumor development and progression , suggesting that prostaglandin regulation of keratinocyte biology is involved in the pathogenesis of epidermal neoplasia . ^^^ In this study , we characterized the expression of COX 1 and COX 2 , as well as keratinocyte proliferation , differentiation , and apoptosis , following acute ultraviolet irradiation in the hairless SKH 1 mouse . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Gene modulation by Cox 1 and Cox 2 specific inhibitors in human colorectal carcinoma cancer cells . ^^^ Cox 1 and Cox 2 specific inhibitors exert chemo preventative activity . ^^^ In this study , human colorectal carcinoma HCT 116 cells were treated with the Cox 1 specific inhibitor SC 560 and the Cox 2 specific inhibitor SC 58125 to evaluate their ability to induce apoptosis , inhibit cell proliferation , inhibit growth on soft agar and modulate gene expression . ^^^ In conclusion , this is the first report to suggest that like sulindac sulfide , the Cox 1 specific inhibitor SC 560 appears to elicit chemo preventative activity by altering gene expression , while the chemo preventative effects of SC 58125 are complex and probably work through these and other mechanisms , such as the inhibition of Cox 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Interestingly , NO ASA induced COX 2 expression , although it had no effect on COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Colonic chloride secretory responses ( in vitro ) were significantly diminished relative to those in controls , a defect that was reversed by pre exposure to a selective COX 2 inhibitor ( celecoxib ) but not to a selective COX 1 inhibitor ( SC 560 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These studies have used ' traditional ' NSAIDs and their metabolites which either do not inhibit COX , are non selective for the COX isoforms or selectively inhibit COX 1 over COX 2 , and recently developed NSAIDs that are highly selective for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS AND RESULTS : Apolipoprotein E deficient ( apoE / ) mice fed a 1 % cholesterol diet were treated with a selective COX 1 inhibitor ( SC 560 ) , a selective COX 2 inhibitor ( SC 236 ) , or vehicle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A novel series of benzo 1 , 3 dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase 2 ( COX 2 ) and cyclooxygenase 1 ( COX 1 ) inhibition in human whole blood ( HWB ) . ^^^ Mono or difluoro substitution at meta position ( s ) , as in 22c and 22h , was advantageous for both in vitro COX 2 potency and selectivity ( e . g . , COX 2 IC ( 50 ) for 22c = 1 microM and COX 1 IC ( 50 ) for 22c = 20 microM in HWB assay ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed that the methanolic extract of adlay seed inhibited basal and TPA induced COX 2 expression in a dose dependent fashion , whereas COX 1 expression was not affected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The analgetic and antiphlogistic effect results from the inhibition of COX 2 , whereas the inhibition of COX 1 is responsible for the majority of side effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We also performed in vitro experiments with fibroblasts derived from wild type ( WT ) , COX 1 ( / ) and COX 2 ( / ) mice , which demonstrated that COX 2 is required for Ti wear debris induced PGE 2 production . ^^^ Pharmacology studies that utilized the COX 1 selective inhibitor SC 560 , the COX 2 selective inhibitor celecoxib , and the nonselective COX inhibitor indomethacin confirmed these results . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mucosal damage induced by preferential COX 1 and COX 2 inhibitors : role of prostaglandins and inflammatory response . ^^^ Fasted rats were given piroxicam , preferential COX 1 inhibitor ( 10 20 mg / kg ) or meloxicam , preferential COX 2 inhibitor ( 7 . 5 15 mg / kg ) orally . ^^^ These results suggest that the PG derived from both COX 1 and COX 2 pathway plays a beneficial role in the gastroprotection , and thus caution should be exercise in the clinical use of preferential COX 2 inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At slaughter , endometrial tissue was collected to determine endometrial expression levels of GM CSF mRNA , cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) and to evaluate in vitro endometrial secretion of prostaglandin E 2 ( PGE 2 ) secretion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of Cox 1 and Cox 2 also were evaluated in cultured ovarian surface epithelial cells prepared from ovarian tissue specimens removed from patients who underwent prophylactic surgery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Six major groups of rats with gastric ulcers were used : ( 1 ) vehicle ( saline ) ; ( 2 ) streptozotocin alone ; ( 3 ) insulin ( 4 IU / day intraperitoneally ) ; ( 4 ) streptozotocin plus insulin ; ( 5 ) pentoxifylline , an inhibitor of synthesis and release of tumor necrosis factor alpha ( TNF alpha ) ; and ( 6 ) aspirin , a non selective inhibitor of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) , and rofecoxib , the highly selective COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OVCAR 3 cells showed a constitutive expression of COX 1 and an induction of high levels of COX 2 and PGE ( 2 ) after stimulation with interleukin 1beta . ^^^ In OVCAR 3 cells , PGE ( 2 ) production was inhibited by NS 398 in concentrations of 1 microM and by a COX 2 specific silencing RNA ( siRNA ) , while a COX 1 specific siRNA did not have an effect . ^^^ Neither COX 1 nor COX 2 specific siRNAs had an effect on cell proliferation of OVCAR 3 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Their COX 2 selectivity , however , has raised concerns regarding their cardiovascular safety , since they do not inhibit COX 1 , the isoform of the enzyme that is active in thrombosis and vasoconstriction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of cyclooxygenases ( COX 1 and COX 2 ) has provided a new insight into the involvement of prostaglandins in the clinical effectiveness and gastrointestinal toxicity of NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The clinical efficacy of NSAIDs is primarily related to the inhibition of COX 2 , whereas much of the toxicity is related to COX 1 inhibition . ^^^ Selective COX 2 inhibitors ( coxibs ) that spare COX 1 at therapeutic doses are more effective than placebo and as effective as other NSAIDs for relief of symptoms of OA and RA , and have significantly improved gastrointestinal safety and tolerability . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The objective of this study was to investigate this putative mechanism by examining the effect of selective COX 2 inhibitors ( Celebrex , DFU , NS 398 ) and COX 1 inhibitors ( Aspirin ) on the growth of two human oral carcinoma cell lines ( OEC M 1 and KB ) and one normal fibroblast cell line ( NF ) . ^^^ The results show that the growth of these cell lines is inhibited by three COX 2 selective inhibitors but not by any COX 1 selective inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
HepG 2 and Hep3B cells do not express COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This 35 kb mitochondrial genome contains the genes encoding ATP synthase subunits 6 , 8 , and 9 ( atp 6 , atp 8 , and atp 9 ) , cytochrome oxidase subunits 1 , 2 , and 3 ( cox 1 , cox 2 , and cox 3 ) , apocytochrome b ( cob ) , reduced nicotinamide adenine dinucleotide ubiquinone oxireductase subunits ( nad 1 , nad 2 , nad 3 , nad 4 , nad4L , nad 5 , and nad 6 ) , ribosomal protein of the small ribosomal subunit ( rps ) , 28 tRNAs , and small and large ribosomal RNAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two COX isoforms : COX 1 is constitutively expressed in a number of cell types and is involved in the homeostatic functions of prostaglandins , whereas COX 2 is inducible by a variety of proinflammatory stimuli , such as cytokines and lipopolysaccharide . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Known NSAIDs were classified as COX 1 or COX 2 selective based on their activity in a platelet aggregation experiment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therefore , we examined the expression pattern of cyclooxygenase 1 ( COX 1 ) , COX 2 , and microsomal prostaglandin E synthase 1 ( mPGES 1 ) , as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux . ^^^ We examined histological changes and expression of COX 1 , COX 2 , mPGES 1 , and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription polymerase chain reaction . ^^^ RESULTS : Normal control oesophageal tissues showed COX 1 expression in subepithelial stromal cells , including endothelial cells and muscular cells , and did not reveal expression of COX 2 or mPGES 1 . ^^^ In the case of squamous cell lesions , immunoreactivity of COX 1 was similar to that of normal lesions , and COX 2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer . mPGES 1 was highly expressed in stromal cells with COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , we explored vasopressin regulation of medullary COX 2 and COX 1 expression acutely and chronically in rats . ^^^ Medullary COX 1 expression was moderately lower and COX 2 expression was significantly lower in adult male Brattleboro rats than age matched Long Evans controls . ^^^ Chronic treatment of Brattleboro rats with vasopressin for 1 wk led to a decrease in urine volume and a moderate increase in medullary COX 1 ; in contrast , medullary COX 2 expression was almost undetectable in untreated rats but was dramatically up regulated with vasopressin treatment and was accompanied by increased urinary prostaglandin E ( 2 ) excretion . ^^^ Further investigation revealed that both V 1 and V 2 receptors were involved in chronic medullary COX 1 and COX 2 up regulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Surprisingly , both COX 2 ( celecoxib ; sc 125 ) or COX 1 ( sc 560 ) selective compounds significantly increased Abeta 42 secretion , and either did not alter ( sc 560 ; sc 125 ) or reduced ( celecoxib ) Abeta 40 levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we evaluated the effectiveness of the select COX 1 and COX 2 inhibitors in preventing mammary tumor development in HER 2 / neu transgenic mice . ^^^ At 4 weeks of age , female HER 2 / neu mice were fed a # 5020 rodent diet supplemented with 900 ppm celecoxib , a COX 2 inhibitor , 64 ppm of SC 560 , a COX 1 inhibitor , or the unsupplemented # 5001 diet ( control ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Eicosanoids constitute a large family of biologically active lipid mediators that are produced by two enzyme classes , cyclooxygenases ( COX 1 and COX 2 ) and lipoxygenases ( 5 LO , 12 LO , and 15 LO ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Whereas COX 1 expression was unaltered in all investigated groups , a significant upregulation of COX 2 mRNA was detected in sural nerves from patients with GBS , CIDP , or VN but not in control subjects with noninflammatory disorders . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The incorporation of [ methyl 3H ] choline and [ 32P ] orthophosphate to PC was determined in the absence and presence of SC 560 and NS 398 , COX 1 and COX 2 specific inhibitors . ^^^ PC synthesis was highly sensitive to COX 2 inhibition , while COX 1 inhibition only reduced PC synthesis at high SC 560 concentration . ^^^ Papillary synthesis of PGD ( 2 ) was only detected in nuclear fraction where it was blocked by COX 2 inhibitor NS 398 , but not by COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dichloromethane and 90 % methanol extracts of different parts of 6 Amaryllidaceae species were investigated for anti inflammatory ( COX 1 and COX 2 ) , antibacterial and mutagenic ( Salmonella / microsome test strain TA 98 ) activities . ^^^ In the anti inflammatory assay , CH ( 2 ) Cl ( 2 ) extracts , resuspended at 500 microg / ml , from different parts of all species under investigation , inhibited activity of both COX 1 and COX 2 by at least 70 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the expression of cyclooxygenase 2 ( COX 2 ) and COX 1 mRNAs during longterm Helicobacter pylori infection of the Mongolian gerbil ( 18 months ) as well as the effect of eradication therapy and the cag pathogenicity island on COX mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenases COX 1 and COX 2 catalyze the first committed step of prostaglandin synthesis from arachidonic acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) mRNA expression was elevated in older kidneys , associated with increased protein expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A non selective cyclooxygenase inhibitor indomethacin ( 2 mg / kg i . p . or 10 microg i . c . v . ) , piroxicam ( 0 . 02 and 0 . 2 microg i . c . v . ) a more potent antagonist of constitutive cyclooxygenase ( COX 1 ) and compound NS 398 ( 0 . 1 and 1 . 0 microg i . c . v . ) , a selective inhibitor of inducible cyclooxygenase ( COX 2 ) were given 15 min before histamine and histamine receptor agonists . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of COX have been identified : COX 1 and COX 2 . ^^^ We examined the expression of COX 1 and COX 2 in esophageal normal mucosa , dysplasia and squamous cell carcinoma ( SCC ) . ^^^ METHODS : The expression of COX 1 and COX 2 in 80 surgically removed esophagi due to SCC , as well as in 5 human esophageal SCC cell lines was analyzed , using immunohistochemistry and Western blot analyses . ^^^ RESULTS : COX 1 and COX 2 were variably expressed in the SCC cell lines . ^^^ CONCLUSIONS : COX 1 is expressed in normal esophageal mucosa and is occasionally induced in well differentiated SCC , whereas COX 2 expression is more characteristic of dysplasia and carcinoma than of normal mucosa , implying a possible association with cell differentiation in the former , and esophageal tumorigenesis in the latter . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In randomized groups of Wistar rats , the effect inhibitor of selective NASAID over the COX 1 , COX 2 and COX 3 the synchronizes inhibition of COX 1 and COX 2 , COX 1 and COX 3 , COX 2 and COX 3 , and COX 1 , COX 2 and COX 3 were studied . ^^^ The conclusions were that the selective inhibition of COX 1 , COX 2 and COX 3 no given gastrointestinal damage ; the synchronizes inhibition of COX 1 and COX 2 given preferential gastric damage ; in contrast the inhibition of COX 2 and COX 3 given massive necrosis preferential in small intestine . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both the 2 ' hydroxy LM 4108 and 2 ' oxo LM 4108 metabolites were synthesized and found to be equipotent to the parent compound with regard to COX 2 inhibitory potency and selectivity [ 2 ' hydroxy LM 4108 : IC ( 50 ) ( COX 2 ) = 0 . 06 microM , IC ( 50 ) ( COX 1 ) > 66 microM ; 2 ' oxo LM 4108 : IC ( 50 ) ( COX 2 ) = 0 . 05 microM , IC ( 50 ) ( COX 1 ) > 66 microM ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The decrease was accompanied by a 50 60 % decrease in mRNA and protein levels of COX 2 , but no change in these levels in COX 1 or in PGE synthase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme ( COX 1 and COX 2 ) have been identified . ^^^ COX 1 is constitutively expressed and considered to be a housekeeping gene , while COX 2 is not usually detectable in normal tissues , but can be readily induced in processes like inflammation , reproduction and carcinogenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
EGF administration increased both COX 1 ( p < . 001 ) and COX 2 ( p < . 01 ) , but both enzymes were blocked by ETOH . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Isoform 1 ( COX 1 ) is constitutively expressed in most tissues , whereas cyclooxygenase 2 ( COX 2 ) is rapidly induced by a variety of different stimuli . ^^^ In this study , we have quantitatively analyzed mRNA expression of COX 1 and COX 2 and protein distribution during corneal reparative processes after wound . ^^^ In normal corneas COX 1 is expressed throughout the cornea in the whole tissue , while COX 2 is strongly expressed in stromal keratocytes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin ( IND ) , an inhibitor preferentially acting on COX 1 , as well as nimesulide ( NIM ) and celecoxib ( CECOX ) , i . e . preferential and selective inhibitor of COX 2 , respectively , administered icv almost completely blocked the antinociceptive effect of ACETA in Randall Selitto method . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
At 100 microg / mL , compounds 2 , 3 , and 4 inhibited the COX 2 enzyme by 11 , 12 , and 10 % , respectively , but did not show activities on the COX 1 enzyme . ^^^ Compounds 6 , 7 , and 8 at 100 microg / mL inhibited the COX 1 enzyme by 98 , 99 , and 98 % , respectively , and the COX 2 enzyme by 0 , 47 , and 72 % , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Celecoxib ( Celebrex ) , valdecoxib ( Bextra ) , and rofecoxib ( Vioxx ) are nonsteroidal antiinflammatory drugs ( NSAIDs ) due to selective inhibition of inducible cyclooxygenase COX 2 while sparing inhibition of constitutive COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To address this question , we determined the effects of camptothecin induced apoptosis on three lung cancer cell lines which over express COX 1 ( CORL 23 ) , COX 2 ( MOR P ) and neither isoform ( H 460 ) , and determine if these effects were prostaglandin mediated . ^^^ Camptothecin induced apoptosis in all three cell lines independently of COX 1 or COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , sulindac sulfide ( SSD ) ( which inhibits Cox 1 and Cox 2 ) 0 200 microM or sulindac sulfone ( SSN ) 0 500 microM ( without significant activity against Cox 1 or Cox 2 ) caused identical decreases in cell number and increases in apoptosis in HT 29 and HCT 116 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biosynthesis of TXA ( 2 ) in PC 3 cells was dependent on COX 2 , and to a lesser extent , COX 1 . ^^^ Treatment of PC 3 cells with a COX 1 selective inhibitor , piroxicam , reduced TXA ( 2 ) synthesis by approximately 40 % , while the COX 2 specific inhibitor NS 398 reduced TXA ( 2 ) production by approximately 80 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 mRNA expression was highly inducible in the mesenteric lymph nodes , whereas COX 1 mRNA levels were constitutive . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed that expression of COX 2 and iNOS , but not COX 1 , decreased significantly in the spinal cords of salicylate treated rats compared with vehicle treated controls ( P < 0 . 05 ) and this finding was paralleled by immunohistochemical observations . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In most tissues , COX 1 is a constitutive enzyme involved in prostaglandin mediated physiological processes , whereas COX 2 is thought to be induced by inflammatory stimuli . ^^^ We have investigated the relative abundance of COX 1 and COX 2 mRNAs in MIN 6 cells , a mouse insulin secreting cell line , and in primary mouse and human islets . ^^^ We found that COX 2 was the dominant isoform in MIN 6 cells , but that COX 1 mRNA was more abundant than that of COX 2 in freshly isolated mouse islets . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
An ethanol extract of this plant was evaluated in vitro for anti inflammatory activities on cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , 5 lipoxygenase ( 5 LO ) and phospholipase A ( 2 ) ( PA ( 2 ) ) . ^^^ The ethanol extract of Tinospora smilacina showed inhibitory activities on COX 1 , COX 2 , 5 LO and PA ( 2 ) with the IC ( 50 ) values of 63 . 5 , 81 . 2 , 92 . 1 and 30 . 5 micro g / mL respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TNF alpha markedly increased COX 2 expression and PGE 2 synthesis in a time and concentration dependent manner , whereas COX 1 remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These effects may be due to overlapping roles of COX 1 and COX 2 in physiological and pathophysiological processes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Licofelone is a competitive inhibitor of 5 LOX , COX 1 and COX 2 that is currently being developed for the treatment of osteoarthritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , a selective COX 1 inhibitor , SC 560 , a selective COX 2 inhibitor , NS 398 , and indomethacin significantly attenuated hepatic responses to LPS including microcirculatory dysfunction and release of ALT and TNF alpha . ^^^ In conclusion , these results suggest that TXA ( 2 ) is involved in LPS induced hepatic microcirculatory dysfunction partly through the release of TNF alpha , and that TXA ( 2 ) derived from COX 1 and COX 2 could be responsible for the microcirculatory dysfunction during endotoxemia . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : Cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) play important roles in normal physiology and are often dysregulated in neoplastic tissues . ^^^ The present study determines whether COX 1 and COX 2 are expressed in ovarian cancers and whether the pattern of expression of these enzymes reveals clues to their roles in this cancer . ^^^ METHODS : The expression of COX 1 and COX 2 proteins in 9 normal human ovaries , in 137 cases of ovarian cancers of epithelial origin ( 83 primary and 54 metastatic ) , and in 7 ovarian cancer cell lines was examined by immunohistochemistry and western analysis . ^^^ CONCLUSION : COX 1 and COX 2 were expressed in every type of ovarian epithelial cancer , suggesting that each may contribute to the cancer development or progression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the expression of COX enzymes , COX 1 and COX 2 , in the brain by use of murine models of CM and of malaria without cerebral involvement . ^^^ Although COX 1 mRNA was induced in the brain in both models of malaria , COX 2 mRNA was induced specifically in CM . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) and COX 2 mediate the rate limiting step in arachidonic acid metabolism . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases ( Cox 1 and Cox 2 ) are the enzymes responsible for prostanoid production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Deguelin strongly inhibited COX 2 expression in squamous HBE cells , without affecting the COX 1 protein level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of colchicine and hydroxychloroquine on the cyclo oxygenases COX 1 and COX 2 . ^^^ METHODS : Measurement of COX 1 and COX 2 activity was performed by using whole blood assay . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase isoenzymes , COX 1 and COX 2 , catalyze the formation of prostaglandins , thromboxane , and levuloglandins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Traditional Non Steroidal Anti Inflammatory Drugs ( NSAIDs ) are nonselective inhibitors of the COX enzyme , of which two isoforms are known to exist COX 1 and COX 2 . ^^^ Selective COX 2 inhibitors were designed to inhibit the production of COX 2 dependent inflammatory prostanoids and to leave intact the cytoprotective COX 1 products . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prior to the discovery of cyclooxygenase 2 ( COX 2 ) , a beneficial association was shown between chronic usage of non steroidal anti inflammatory drugs ( NSAIDs ) , that non selectively inhibit both cyclooxygenase 1 ( COX 1 ) and COX 2 , and prevention of colorectal cancer . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis of the cancer lines revealed significantly higher expression of COX 1 in CORL 23 line and COX 2 in two NSCLC cell lines ( MOR / P ; A 549 ) compared with the expression of COX 1 and COX 2 in cultured normal bronchial epithelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The rat GMC spontaneously expressed type 1 cyclooxygenase ( COX 1 ) , but not COX 2 . ^^^ Collectively , the proinflammatory cytokines could enhance COX 1 but not COX 2 expression in GMC leading to increased PGE 2 and TXB 2 production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAID ) inhibit cyclooxygenase ( COX ) enzymes , which exist in at least two isoforms , COX 1 and COX 2 . ^^^ Aspirin and older agents in this class are nonselective inhibitors of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , prostacyclin generation is both COX 1 and COX 2 dependent . ^^^ The inhibition of COX 1 and COX 2 did not prevent the production of 8 epi PGF ( 2alpha ) , suggesting that this is not enzymatically derived . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Importantly , Phase 3 occurs despite a drastic decrease in the expression of COX 1 and 2 in both the brain and periphery , thus suggesting that transcriptional up regulation of COX 2 is not an obligatory mechanism of PGE 2 dependent inflammatory responses at later stages . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Loxoprofen , its trans alcohol and cis alcohol metabolites were evaluated for selectivity of inhibition of COX 2 over COX 1 . ^^^ The ( 2S , 1 ' R , 2 ' S ) trans alcohol derivative was found to be the most active metabolite and to be a potent and nonselective inhibitor of COX 2 and COX 1 in both enzyme and human whole blood assays . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the role of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in the development of bladder transitional cell carcinoma . ^^^ Immunohistochemistry and RT PCR were performed to study the expression of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After multiple urethane injections into cPLA 2 null mice and wild type littermates , the number of lung tumors was determined . cPLA 2 null mice developed 43 % fewer tumors ( from 16 + / 2 to 9 + / 2 tumors / mouse ; P < 0 . 05 ) than wild type littermates . cPLA 2 , COX 1 , COX 2 and microsomal prostaglandin E 2 synthase ( mPGES ) , examined by immunohistochemistry , are present in alveolar and bronchiolar epithelia and in alveolar macrophages in lungs from naive mice and tumor bearing mice . ^^^ No differences were detected in the contents of COX 1 , COX 2 and mPGES between wild type and cPLA 2 null mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non steroidal anti inflammatory drugs inhibit PG synthesis via COX 1 and / or COX 2 isoenzymes and may inhibit periodontal destruction . ^^^ METHODS : Gingival fibroblasts ( 2 . 5 10 10 ( 4 ) ) from healthy or severe periodontitis patients were cultured in serum free medium , with or without IL 1beta ( 10 ( 11 ) M ) for 24 hours , with or without the COX 1 / 2 inhibitor indomethacin or the selective COX 2 inhibitors NS 398 , celecoxib , or rofecoxib . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Paracetamol and salicylate are weak inhibitors of both isolated cyclooxygenase 1 ( COX 1 ) and COX 2 but are potent inhibitors of prostaglandin ( PG ) synthesis in intact cells if low concentrations of arachidonic acid are available . ^^^ At low concentrations of arachidonic acid , COX 2 is the major isoenzyme involved in PG synthesis when both COX 1 and COX 2 are present in cells . ^^^ Therefore , paracetamol and salicylate may selectively inhibit PG synthesis involving COX 2 because the lower flux through this pathway produces lesser levels of the hydroperoxide , PGG ( 2 ) , than the pathway involving COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGs are produced by two distinct isoforms of cyclooxygenase ( COX ) , including constitutively expressed COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX activity assays were carried out with purified enzymes , COX 1 ( ram seminal vesicles ) , COX 2 ( sheep placenta ) and with human THP 1 cells , differentiated for 24 h with PMA ( 50 nM ) . ^^^ N combination as well as its constituent mother tinctures of Arnica montana , Sanguinaria canadensis and Rhus toxicodendron ( Toxicodendron quercifolium ) showed distinct inhibitory effects on the production of LTB 4 by 5 LOX ( IC 50 values of 10 , 20 , 2 and 5 microg / ml respectively ) and on the synthesis of PGE 2 by COX 1 ( IC 50 values of 50 , 80 , 40 and 20 microg / ml respectively ) and COX 2 enzymes ( IC 50 values of 60 , 110 , 50 and 20 microg / ml respectively ) . ^^^ The mother tincture of Solanum dulcamara inhibited the production of PGE 2 by COX 1 ( IC 50 40 microg / ml ) and COX 2 ( IC 50 150 microg / ml ) but not production of leukotriene LTB 4 by 5 LOX . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Studies with isolated ovine COX 1 and COX 2 enzymes showed that the curcuminoids had significantly higher inhibitory effects on the peroxidase activity of COX 1 than that of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The 5 oxo ETE responses were also inhibited by indomethacin and SC 560 [ a cyclooxygenase ( COX 1 ) inhibitor ] pretreatments but not by NS 398 ( a selective COX 2 inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 and the topical effect in NSAID induced enteropathy . ^^^ We examined the role of COX 1 , COX 2 and the so called topical effect of acidic NSAIDs . ^^^ We found that COX 1 or COX 2 inhibition and the topical effect alone do not damage the GI tract . ^^^ Dual inhibition of COX 1 and COX 2 results in intestinal inflammation similar to that caused by Indomethacin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent studies suggest that non specific NSAIDs , which inhibit both COX 1 and COX 2 isoforms , delay bone healing . ^^^ The objectives of this study were 2 fold ; first , to measure the relative changes in the normal expression of COX 1 and COX 2 mRNAs over a 42 day period of fracture healing and second , to compare the effects of a commonly used non specific NSAID , ketorolac , with a COX 2 specific NSAID , Parecoxib ( a pro drug of valdecoxib ) , on this process . ^^^ Total RNA was prepared from the calluses obtained prior to fracture and at 1 , 3 , 5 , 7 , 10 , 14 , 21 , 35 and 42 days post fracture and levels of COX 1 and COX 2 mRNA were measured using real time PCR . ^^^ While the relative levels of COX 1 mRNA remained constant over a 21 day period , COX 2 mRNA levels showed peak expression during the first 14 days of healing and returned to basal levels by day 21 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CT 26 cells express both COX 1 and COX 2 and metabolize arachidonic acid to PGE ( 2 . ) Treatment with indomethacin , or COX selective inhibitors , prevents PGE ( 2 ) biosynthesis and CT 26 cell proliferation . ^^^ Indomethacin or COX 2 inhibitors , but not COX 1 inhibitors , reduced the size and number of CT 26 derived tumors in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effect of sinomenine on cyclooxygenase activity and the expression of COX 1 and COX 2 mRNA in human peripheral monocytes ] . ^^^ OBJECTIVE : To observe in vitro the effect of Sinomenine , a pure alkaloid extracted from the chinese medical plant Sinomenium acutum on the activity of cyclooxygenase ( COX 1 and COX 2 ) and the expression of COX 1 and COX 2 mRNA . ^^^ And by RT PCR , both COX 1 and COX 2 mRNAs were detected in Mononuclear leukocytes after incubation for different hours with drug ( sinomenine or indomethacin ) or not . ^^^ L 1 ) inhibited the expression of both COX 1 and COX 2 mRNAs by RT PCR with beta actin as reference . ^^^ CONCLUSION : In contrast with indomethacin , Sinomenine shows a preferential inhibitory effect on COX 2 over COX 1 , These results suggest that Sinomenine is a selective COX 2 inhibitor , which may be directly related to suppressing cyclooxygenase activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : The purpose of this work was to determine the in vitro effect of Rofecoxib and specific COX 1 and COX 2 inhibitors in regards to cell growth and apoptotic and necrotic activity . ^^^ We hypothesized that in vitro treatment with both COX 1 and COX 2 inhibitors would significantly reduce cellular proliferation of bladder cancer cells by apoptotic pathways . ^^^ Catechin ( COX 1 inhibitor ) and NS 398 ( COX 2 inhibitor ) were used at doses of 50 and 100 microM . ^^^ CONCLUSIONS : Selective COX 2 inhibition , using the well tolerated and commercially available Rofecoxib ( VIOXX ) and specific COX 1 and 2 inhibitors , reduced the growth of human bladder cancer in vitro by apoptotic mechanisms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective inhibition of either COX isoform resulted in increased secretion of tumor necrosis factor alpha ( TNF alpha ) ; however , this effect was much greater with the COX 1 than with the COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
TNF alpha treatment significantly increased cytosolic phospholipase A ( 2 ) and cyclooxygenase 2 ( COX 2 ) protein expression and PGE ( 2 ) level but did not affect the protein levels of EGF , basic fibroblast growth factor , and COX 1 in RGM 1 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immuno localization of COX 1 and COX 2 in the rat molar periodontal tissue after topical application of lipopolysaccharide . ^^^ The purpose of the study was to demonstrate the dynamic changes of immuno localization of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in rat periodontal tissue after topical application of lipopolysaccharide ( LPS : 5 mg / ml in physiological saline ) from Escherichia coli into the rat molar gingival sulcus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The results demonstrated marked synergistic interaction between naproxen and tramadol and such interaction involved opioid as well as non opioid mechanisms of tramadol and inhibition of COX 1 but not COX 2 by naproxen . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Its two isoenzymes , COX 1 and COX 2 , have different functions . ^^^ The recent development of specific COX 2 inhibitors , which retain the same anti inflammatory efficacy but do not have the gastric side effects of conventional treatment related to COX 1 inhibition , gives them a greater safety margin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In isolated perfused glomerular preparations , renin release induced by macula densa perfusion with a low chloride solution was inhibited by a COX 2 inhibitor but not a COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our data indicate an involvement of both COX 1 and COX 2 , and the MEK extracellular signal regulated kinase and p 38 MAP kinase signaling pathways in the PAR 2 and PAR 1 triggered relaxation of mouse airway tissue , and substantiate a role for PAR 2 in regulating both the trachea and bronchial responsiveness in the mouse lung . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CLINICAL RELEVANCE : The role of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) during vascular recurrent stenosis and atherosclerosis is not clear yet . ^^^ However , the concurrent inhibition of endogenous nitric oxide generation and COX 1 or COX 2 causes overshooting neointimal hyperplasia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) enzymes , on lipid peroxidation , and on the proliferation of human colon ( HCT 116 ) , breast ( MCF 7 ) , lung ( NCIH 460 ) , and central nervous system ( CNS , SF 268 ) cancer cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , inhibition of cyclooxygenase 1 ( COX 1 ) ( but not COX 2 ) inhibited ES uptake . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We aimed to determine whether microsomal and cytosolic PGES ( mPGES 1 and cPGES ) colocalize and coordinate activity with either COX 1 or COX 2 in brain tissue , particularly during development . ^^^ In microsomal membranes from the postnatal brain and cerebral microvessels of mature animals , cPGES m colocalized with both COX 1 and COX 2 , whereas mPGES 1 was undetectable in these microsomes . ^^^ Accordingly , in this cell compartment , cPGES could coordinate its activity with COX 2 and COX 1 ( partly inhibited by NS 398 ) ; albeit in microsomes of the brain microvasculature from newborns , mPGES 1 was also present . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) enzymes ( COX 1 and COX 2 ) are key enzymes of prostaglandin ( PG ) biosynthesis . ^^^ Nonselective non steroidal anti inflammatory drugs ( NSAIDs ) inhibit the enzymatic activity of both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated whether n LDL or Ox LDL modulate cyclooxygenase 1 and 2 ( Cox 1 and Cox 2 ) expression and prostaglandins release in human endothelial cells via an MAPK dependent pathway . ^^^ Real time PCR , western blotting and immunocytochemistry were used to investigate Cox 1 and Cox 2 expression . ^^^ The effect was specific for Cox 2 , as Cox 1 expression was not modulated either by n LDL or by Ox LDL . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , we measured the levels of proteins whose abnormal expression has been associated with neurodegeneration such as amyloid precursor protein ( APP ) , presenilin 1 and 2 ( PS 1 , PS 2 ) , and cyclooxygenases ( COX 1 and COX 2 ) . ^^^ Levels of hippocampal COX 2 protein and mRNA were significantly decreased whereas COX 1 remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To describe cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) and 5 lipoxygenase ( 5 LOX ) expression in muscle tissue in patients with idiopathic inflammatory myopathies ( IIM ) dermatomyositis ( DM ) and polymyositis ( PM ) and to find out if any differences between affected and non affected muscles detected by MRI exist . ^^^ In situ hybridization with antisense mRNA probes was employed to detect COX 1 , COX 2 and 5 LOX mRNA . ^^^ RESULTS : Expression of COX 1 , COX 2 , and 5 LOX mRNA was found in all samples in the muscle cells , inflammatory cells and in vessels . ^^^ CONCLUSION : Expression of COX 1 , COX 2 and 5 LOX mRNA was observed for the first time in muscle tissues from IIM patients . ^^^ This expression was increased in affected tissues detected by MRI , which may suggest a role of COX 1 , COX 2 , and 5 LOX in the pathogenesis of IIM . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 isoenzymes were both highly expressed in LMM 3 cells , and we observed that indomethacin was more effective than NS 398 to inhibit prostaglandin E 2 ( PGE 2 ) synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 2 was induced transiently in a biphasic manner upon the triggering of the differentiation and maturation phases while COX 1 was constitutive . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we present the expression of COX 1 and COX 2 mRNA and protein in striatum following 1 methyl 4 phenyl 1 , 2 , 3 , 6 tetrahydropyridine ( MPTP ) administration to mice . ^^^ We have found that COX 1 mRNA expression is not changed following MPTP administration , but COX 2 gene and protein expression in striatum increases from the 3rd to the 7th and 14th days , and diminishes on the 21st day . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several polymorphisms in ALOX and COX genes have been identified , including G 1752A , G 1699A and Glu254Lys in ALOX 5 ; Gln261Arg in ALOX 12 ; Leu237Met and Val481Ile in COX 1 ; and C 645T and Val511Ala in COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have studied the expression of enzymes involved in metabolism of PGE ( 2 ) and PGF ( 2alpha ) , cyclooxygenase 1 ( COX 1 ) and COX 2 , PG synthases ( PGES and PGFS ) , PG 15 dehydrogenase , and PG transporter as well as PGE ( 2 ) ( EP 2 and EP 3 ) and PGF ( 2alpha ) receptors . ^^^ IFNtau influences cell specific expression of COX 2 , PGFS , EP 2 , and EP 3 in endometrium , myometrium , and CL in a spatio temporal and tissue specific manner , whereas it does not alter COX 1 , PGES , PG 15 dehydrogenase , PG transporter , or PGF ( 2alpha ) receptor expression in any of these tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we compared the effects of a selective COX 2 inhibitor ( celecoxib ) , a preferential COX 1 inhibitor ( piroxicam ) , and a nonnarcotic analgesic ( metamizol ) on normal gastric mucosa of rats and , on the other hand , in a setting of preexisting acute gastric lesions induced by 0 . 6 N hydrochloric acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A novel Src tyrosine kinase inhibitor , Herbimycin A ( HERB ) , reduced COX 2 mRNA levels as well as PGE ( 2 ) production induced by IL 1beta , TNF alpha and IL 6 or a combination of IL 1beta , TNF alpha , IL 6 , whereas COX 1 mRNA levels remained unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression and localization of cyclooxigenases ( Cox 1 and Cox 2 ) in nasal respiratory mucosa . ^^^ INTRODUCTION : Cyclooxygenases 1 ( Cox 1 ) and 2 ( Cox 2 ) play a key role in arachidonic acid metabolism and in the regulation of eicosanoid production . ^^^ METHODS : 36 surgical specimens were immunohistochemically labeled for Cox 1 and Cox 2 . ^^^ RESULTS : Analysis revealed that Cox 1 and Cox 2 were labeled in all 23 inflamed / polypoid tissue specimens and in all 13 controls . ^^^ In chronically inflamed tissue the expression of Cox 1 and Cox 2 was strongly labeled in the respiratory epithelial lining and in mucosal glandular ducts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In monkeys , COX 1 was localized in epithelial cells of the epididymis and vas deferens , whereas COX 2 was dominantly found in epithelial cells of the seminal vesicles . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We report that Cox 1 and Cox 2 expression is highly variable in Dukes ' C tumours , and changes in Cox 1 expression may be of importance . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although much effort has focused on COX 2 inhibition , recent work indicates that COX 1 deletion may be nearly as protective . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
More recently , additional heterogeneity in COX related proteins has been described , with the finding of variants of COX 1 and COX 2 enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
By immunoblotting and reverse transcription polymerase chain reaction , we showed that gamma mangostin concentration dependently inhibited lipopolysaccharide ( LPS ) induced expression of COX 2 protein and its mRNA , but not those of constitutive COX 1 cyclooxygenase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Oxaprozin ' s strong analgesic qualities are particularly useful in painful musculoskeletal conditions such as periarthritis of the shoulder , since it exhibits actions such as inhibition of COX 1 and COX 2 isoenzymes , inhibition of nuclear translocation of NF kappaB and of metalloproteases , and modulates the endogenous cannabinoid system . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exploring QSAR with E state index : selectivity requirements for COX 2 versus COX 1 binding of terphenyl methyl sulfones and sulfonamides . ^^^ An attempt has been made to explore selectivity requirements for cyclooxygenase 2 ( COX 2 ) versus cyclooxygenase 1 ( COX 1 ) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state ( E state ) index and suitable indicator parameters . ^^^ Multiple linear regression analyses produced statistically acceptable equations : the best relation based on ' all possible subsets regression ' for COX 1 binding ( n=18 ) showed predicted variance and explained variance of 0 . 675 and 0 . 777 , respectively , while in case of the best equation for COX 2 binding ( n=38 ) , these values rose to 0 . 842 and 0 . 874 , respectively . ^^^ All three sites are important for COX 2 binding while sites B and C are important for COX 1 binding . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non selective COX inhibitors ( the NSAIDs indomethacin and flunixin , p . o . or i . p . ) , the COX 1 selective inhibitor SC 560 ( s . c . or i . p . ) , and the COX 2 selective inhibitor NS 398 ( s . c . or i . p . ) were evaluated in four experimental models . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dual COX 1 and COX 2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs , as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Not only ibuprofen , aspirin ( 100 microM ) , indomethacin ( 50 microM ) , and selective COX 1 or COX 2 inhibitor ( 10 nM ketrolac or 2 microM NS 398 ) also blocked the Abeta induced increase in neuronal [ Cl ] 1 , though such effects of COX 2 preferring drugs were limited in aggregated Abeta induced changes . ^^^ Further , ibuprofen as well as selective COX 1 or COX 2 inhibitor reduced Abeta induced aggravation of glutamate toxicity as assessed by cell viability . ^^^ These findings suggest that NSAIDs protect neurons from Abeta induced degeneration via inhibition of neuronal COX 1 as well as COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin ( inhibiting both COX 1 and COX 2 ) and specific COX 1 and COX 2 inhibitors reduced rotavirus infection by 85 and 50 % , respectively , as measured by an IFA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 1 and COX 2 in human gastric mucosa was detected by immunohistochemical staining . ^^^ From CSG to GA , IM , dysplasia and finally to gastric cancer , expression of COX 2 showed an ascending tendency , whereas COX 1 expression did not change significantly in the gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These differences were unrelated to cyclooxygenase ( COX ) inhibition since HCT 1026 and HCT 1027 were about seven to eight times less potent than flurbiprofen at inhibiting COX 1 activity and half as potent at inhibiting COX 2 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that during pregnancy PGF ( 2alpha ) production and also protein levels of COX 1 and COX 2 were decreased . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study examined the immunohistochemical expression and localization of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) in synovial tissues from patients with internal derangement ( ID ) or osteoarthritis ( OA ) of the temporomandibular joint ( TMJ ) . ^^^ Synovial tissues from 13 TMJs of 10 patients with ID or OA and from 5 TMJs of 4 patients with fractures were examined for COX 1 and COX 2 expression by immunohistochemical staining using two monoclonal antibodies . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Some of them , more soluble in water , were tested to define the influence on prostaglandin biosynthesis via inhibition of cyclooxygenases ( COX 1 and COX 2 ) by a chemiluminescent method suitable for fast screening . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In mammals , the two COX genes encode a constitutive isoenzyme ( COX 1 ) and an inducible isoenzyme ( COX 2 ) ; both are of significant pharmacological importance . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
SC 560 ( an inhibitor of COX 1 ) decreased the frequency of ACh stimulated exocytotic events by 30 % , but NS 398 ( an inhibitor of COX 2 ) did not . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have recently demonstrated that treatment of ovarian carcinoma cells with endothelin 1 ( ET 1 ) induces expression of both COX 1 and COX 2 , which contributes to vascular endothelial growth factor ( VEGF ) production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins ( PGs ) , generated through the action of cyclooxygenase 1 ( COX 1 ) and COX 2 protect the intestinal stem cells from IR . ^^^ Furthermore , CUGBP 2 expression is higher in COX 1 ( / ) and COX 2 ( / ) mice than wild type controls at basal conditions , which is further increased after IR . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL1beta increased COX 2 and did not alter COX 1 synthesis in SF . 11 Deoxy PGE ( 1 ) , an EP ( 2 ) / EP ( 4 ) agonist , reproduced PGE ( 2 ) action on MCP 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cox 1 gene had a serine as the start codon , while incomplete termination codons mediated by tRNA signals were found for cox 2 , nd 4 and nd 5 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase : COX 1 and COX 2 . ^^^ The ideal nutraceutical would inhibit COX 2 synthesis while preserving COX 1 synthesis . ^^^ The hypothesis for this research was that COX inhibitors would fall primarily into three categories : COX 2 specific inhibition , non specific inhibition ( COX 1 and COX 2 ) , and minimal inhibition . ^^^ The human Cayman COX inhibitor screening assay was used to determine the inhibitory concentration 50 ( IC 50 ) of COX 1 / COX 2 activity of each nutraceutical . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These drugs are defined by their COX 2 selectivity which is supported by a negligible inhibitory potency on platelet COX 1 in vitro and ex vivo after oral intake of maximal therapeutic doses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
With the development of molecular biology , the discovery of two major cyclooxygenase genes ( COX 1 and COX 2 ) was heralded in 1990 , which has subsequently led to the clinical use and development of selective COX 2 inhibitors . ^^^ Splice variants of both COX 1 and COX 2 were first encountered in the early 1990s , as were single nucleotide polymorphisms of COX 1 and 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The biochemical COX 1 / COX 2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Under basal conditions , CLA mix ( 10 microg / mL , 0 to 24 h ) had no significant effect on either COX 1 or COX 2 expression , genes that could be readily induced in response to hemodynamic stimuli . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although AT did not affect COX 1 mRNA levels 1 hour after reperfusion , it inhibited the I / R induced increases in hepatic tissue levels of both PGE ( 2 ) and COX 2 mRNA 6 hours after reperfusion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists in two known isoforms ; a constitutive COX 1 , and COX 2 , which is inducible upon the action of pyrogens . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : Using two animal models to determine which isoform of cyclooxygenase ( COX ) , constitutive COX 1 or inducible COX 2 , is involved in the progression of anterior ocular inflammation . ^^^ Changes in mRNA for COX 1 and COX 2 in conjunctiva were detected by RT PCR . ^^^ RESULTS : In the carrageenan injected model , the dye content of conjunctiva ( 12 . 4 + / 2 . 8 mg / eye ) was significantly increased 4 hours after injection compared to saline injected control rats ( 3 . 7 + / 1 . 1 mg / eye ) . mRNA for COX 2 was significantly increased by 2 hours and gradually increased until 24 hours ; COX 1 mRNA did not show major changes until 24 hours after injection . ^^^ Expression of COX 2 mRNA was increased 1 hour after injection , peaked at 2 hours , and decreased at 4 hours . mRNA for COX 1 did not change by 24 hours . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Interestingly , selective COX 2 inhibition ( NS 398 ) , but not selective COX 1 inhibition ( SC 560 ) , exerted a stimulatory effect on the expression of pro inflammatory cytokines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NOC 7 activated the COX 1 activity but inhibited the COX 2 activity at concentrations ranging from 1 to 50 microM . ^^^ At a low concentration of ONOO ( ) ( 5 microM ) there was enhancement of the COX 1 and 2 activities , but with higher concentrations there was suppression of these two enzyme activities ( COX 1 , at 200 microM ; COX 2 , > 50 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A non selective cyclooxygenase inhibitor indomethacin ( 10 mg / kg i . p . ) , piroxicam ( 2 mg / kg i . p . ) , a more potent antagonist of constitutive cyclooxygenase ( COX 1 ) and compound NS 398 ( 2 mg / kg i . p . ) , a selective inhibitor of inducible cyclooxygenase ( COX 2 ) given 30 min before LPS ( 1 mg / kg i . p . ) significantly diminished both the LPS induced ACTH and corticosterone secretion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) inhibitors indomethacin ( 10 microM ) , NS 398 ( 10 microM , selective for COX 2 ) , and SC 560 ( 100 nM , selective for COX 1 ) caused a marked rightward shift of concentration responses to AA . ^^^ With the use of immunohistochemical analysis , both COX 1 and COX 2 were detected in endothelium and smooth muscle of small mesenteric arteries . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , the effects of the selective COX 1 inhibitor SC 560 and the selective COX 2 inhibitor NS 398 on the production of NO , PGE 2 , and 6 keto PGF1alpha were examined . ^^^ Western blotting was performed to evaluate the expression of COX 1 and COX 2 in the skin at the site of the inflammation . ^^^ Western blot analysis showed that the concentrations of both COX 1 and COX 2 in the skin increased after carrageenan . ^^^ CONCLUSION : The results of the current study suggest that NO activates COX 1 in the early phase of carrageenan and up regulates COX 2 expression in the late phase in the skin , resulting in production of PGE 2 and PGI 2 at the site of inflammation , which would contribute to exacerbation of the inflammatory process . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To evaluate the role of cyclooxygenase 1 and 2 ( COX 1 , COX 2 ) in sulfur mustard induced skin toxicity , we applied the agent to the ears of wildtype ( WT ) and COX 1 and COX 2 deficient mice . ^^^ These findings may indicate that COX 2 participates in the early stages of sulfur mustard induced acute skin toxicity and that COX 1 might exert some protective function against this chemical insult . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 inhibitors have been shown to effectively treat a variety of pain conditions in animals and in humans ; however , their efficacy in treatment of acute visceral pain has not been explored . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) superfamily of prostaglandin synthase genes encode a constitutively expressed COX 1 , an inducible , highly regulated COX 2 , and a COX 3 isoform whose RNA is derived through the retention of a highly structured , G + C rich intron 1 of the COX 1 gene . ^^^ The results indicate that while COX 2 remains a major player in propagating inflammmation in AD and in stressed HN cells , COX 3 may play ancillary roles in membrane based COX signaling or when basal levels of COX 1 or COX 2 expression persist . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Green tea constituent epigallocatechin 3 gallate selectively inhibits COX 2 without affecting COX 1 expression in human prostate carcinoma cells . ^^^ Therefore , there is a need to define novel , nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX 2 but not COX 1 inhibitory activity . ^^^ Here , we show that EGCG inhibits COX 2 without affecting COX 1 expression at both the mRNA and protein levels , in androgen sensitive LNCaP and androgen insensitive PC 3 human prostate carcinoma cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis and quantitative reverse transcriptase polymerase chain reaction ( RT PCR ) using TaqMan ( Applied Biosystems , Foster City , CA ) technology were performed to evaluate the expression of cytosolic phopholipase A ( 2 ) ( cPLA ( 2 ) ) , cyclooxygenase 1 ( COX 1 ) , COX 2 , and prostacyclin synthase ( PGIS ) in cultured human myometrial cells prepared from second trimester pregnant women ( n = 3 ) after stimulation with 17beta estradiol . ^^^ Western blot analysis detected cPLA ( 2 ) and COX 1 and PGIS protein expression in the cultured human myometrial cells ; however , COX 2 protein expression was below the detection sensitivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the key enzyme in prostaglandin cascade , is expressed in two isoforms : the constitutive COX 1 and the inducible COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Nonsteroidal anti inflammatory drugs ( NSAIDs ) are nonspecific cyclo oxygenase ( COX 1 / COX 2 ) inhibitors and are associated with gastrointestinal ( GI ) toxicity attributable to COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
More recent work has concerned the role of infiltrating inflammatory cells , the relative roles of cyclooxygenase isoforms , COX 1 and COX 2 and the key involvement of inducible nitric oxide ( NO ) synthase and its product in combination with superoxide , peroxynitrite . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Therapeutic doses of COX 2 specific inhibitors are as effective as nonspecific nonsteroidal anti inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX 1 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Among cytotoxic , antifungal , antibacterial cardioprotective activity resveratrol also demonstrates non selective cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibition . ^^^ In order to find more selective COX 2 inhibitors a series of methoxylated and hydroxylated resveratrol derivatives were synthesized and evaluated for their ability to inhibit both enzymes using in vitro inhibition assays for COX 1 and COX 2 by measuring PGE ( 2 ) production . ^^^ The most potent resveratrol compounds were 3 , 3 ' , 4 ' , 5 tetra trans hydroxystilbene ( COX 1 : IC ( 50 ) =4 . 713 , COX 2 : IC ( 50 ) =0 . 0113 microM , selectivity index=417 . 08 ) and 3 , 3 ' , 4 , 4 ' , 5 , 5 ' hexa hydroxy trans stilbene ( COX 1 : IC ( 50 ) =0 . 748 , COX 2 : IC ( 50 ) =0 . 00104 microM , selectivity index=719 . 23 ) . ^^^ Their selectivity index was in part higher than celecoxib , a selective COX 2 inhibitor already established on the market ( COX 1 : IC ( 50 ) =19 . 026 , COX 2 : IC ( 50 ) =0 . 03482 microM , selectivity index=546 . 41 ) . ^^^ Docking studies on both COX 1 and COX 2 protein structures also revealed that hydroxylated but not methoxylated resveratrol analogues are able to bind to the previously identified binding sites of the enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The metabolite flurbiprofen inhibited plasma COX 1 activity for the duration of the study period ( maximum inhibition at 4 hours ) , whereas COX 2 activity recovered after 6 hours . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selected compounds tested for inhibitory activity against COX 1 and COX 2 enzymes showed good selectivity for COX 2 versus COX 1 enzyme . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although a report suggested a possible role of endothelial COX 1 in the process of angiogenesis , in a recent study , the selective inhibition of COX 2 was shown to strongly inhibit angiogenesis by inducing endothelial cell ( EC ) apoptosis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We report a structural series of N phenylanthranilic acid derivatives and steroid carboxylates that selectively inhibit recombinant AKR1C isoforms but do not inhibit recombinant COX 1 or COX 2 . ^^^ Lead compounds , 4 chloro N phenylanthranilic acid and 4 benzoyl benzoic acid for the N phenylanthranilic acid analogs and most steroid carboxylates , exhibited IC ( 50 ) values that had greater than 500 fold selectivity for AKR1C isozymes compared with COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The differential inhibition of COX 1 and COX 2 is not sufficient to explain the absence of a correlation between in vitro and in vivo effects , especially for 2 aryl propionates , thus indicating the participation of metabolites . ^^^ Using an anti ketoprofen antibody , COX immunoprecipitated from cells exhibited adduct formation for COX 2 but not for COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 expression was constitutive in 9 / 9 pancreatic cancer cell lines , whereas COX 2 and cytosolic phospholipase A 2 ( cPLA 2 ) expression were observed in 4 / 9 cell lines ( BxPC 3 , Capan 2 , Cfpac 1 , and L3 . 6 pl ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVES : To quantify the expression and spontaneous regulation of COX 1 and COX 2 mRNAs in nasal polyps and nasal mucosa by real time PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Biopsies were taken from the gastric antrum and corpus for determination of prostaglandin E 2 ( PGE 2 ) by ELISA and cyclooxygenase ( COX 1 and COX 2 ) and nitric oxide synthase ( eNOS and iNOS ) by western blot . ^^^ COX 1 , COX 2 , eNOS , and iNOS were detectable in all subjects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is the constitutive enzyme responsible for synthesis of protective prostanoids , whereas COX 2 is induced under inflammatory conditions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent investigations indicate that both isoforms , COX 1 and COX 2 , are involved in carcinogenesis . ^^^ RESULTS : The investigated cell lines express COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Specific cyclooxygenase ( COX ) inhibitors were used to identify the role of COX 1 and COX 2 derived PGs . ^^^ The expression and the localization of COX 1 , COX 2 and prostacyclin synthase ( PGIS ) were examined by western blot analysis and immunohistochemistry . ^^^ Prostacyclin was the most abundant PG produced by mouse blastocysts , which expressed COX 1 , COX 2 and PGIS . ^^^ COX 1 , COX 2 and PGIS were expressed in 4 cell stage embryos and beyond ; they were present in the inner cell mass and the trophectoderm of the blastocysts . ^^^ CONCLUSION : Mouse embryos express COX 1 , COX 2 and PGIS which catalyse the formation of PGI 2 ; COX 2 derived PGI 2 plays a critical role in embryo hatching . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Mice with targeted disruption of the COX 2 gene exposed to chronic hypoxia had exacerbated right ventricular end systolic pressure , whereas targeted disruption of COX 1 had no effect . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of a second isoform of cyclooxygenase ( COX ) led to the search for compounds that could selectively inhibit COX 2 in humans while sparing prostaglandin formation from COX 1 . ^^^ Recombinant human COX 1 and COX 2 were used to screen for new highly potent and in vitro selective COX 2 inhibitors and compare kinetic mechanisms of binding and enzyme inhibition with other COX inhibitors . ^^^ Valdecoxib showed similar activity in the human whole blood COX assay ( COX 2 IC ( 50 ) = 0 . 24 microM ; COX 1 IC ( 50 ) = 21 . 9 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These data suggest that structural elements responsible for COX 1 and COX 2 inhibition do not correlate well with those responsible for inhibiting COX 2 and iNOS gene expression , but elements capable of inhibiting COX 2 and iNOS gene expression also contribute to inhibition of TPA induced ODC activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : While COX 1 protein was observed at each stage of erythroblast development , COX 2 protein was induced at later stages through a p38 / MAPK dependent pathway . ^^^ COX 1 and COX 2 were also observed in erythrocytes by immunostainings , although COX expression was confined to a fraction of circulating erythrocytes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of the present study was to investigate the localization of the FP , EP ( 1 ) and EP ( 3 ) prostanoid receptors as well as the COX 1 and COX 2 enzymes in the cochlea of guinea pig and man . ^^^ The COX 1 enzyme seems to be constitutively expressed in the cochlea in contrast to COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The in vitro cyclooxygenase ( COX 1 ) catalyzed prostaglandin biosynthesis assay of THA gave an IC ( 50 ) value of 29 . 5 microM ( COX 1 ) and 40 . 5 % inhibition at 100 microg / mL ( COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , COX 2 ( / ) mice show increased levels of lung PGE ( 2 ) , compared with wild type mice after injury ( P < 0 . 05 ) , because of compensatory up regulation of COX 1 , which appears to be associated with macrophage / monocytes but not fibroblasts derived from these mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Strains were constructed lacking Cox 1 ( a previously characterized cytochrome c oxidase ) , Cox 2 , or both , which all grew diazotrophically . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin mediated control of rat brain kynurenic acid synthesis opposite actions by COX 1 and COX 2 isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro COX 1 and COX 2 isozyme inhibition structure activity studies identified 1 , 1 diphenyl 2 ( 4 methylsulfonylphenyl ) hex 1 ene as a highly potent ( IC ( 50 ) = 0 . 014 microM ) , and an extremely selective [ COX 2 selectivity index ( SI ) > 7142 ] , COX 2 inhibitor that showed superior anti inflammatory ( AI ) activity ( ID ( 50 ) = 2 . 5 mg / kg ) relative to celecoxib ( ID ( 50 ) = 10 . 8 mg / kg ) . ^^^ COX 1 and COX 2 inhibition studies showed that ( Z ) 1 ( 4 acetoxyphenyl ) 1 phenyl 2 ( 4 methylsulfonylphenyl ) but 1 ene [ ( Z ) 13b ] is a potent ( COX 1 IC ( 50 ) = 2 . 4 microM ; COX 2 IC ( 50 ) = 0 . 03 microM ) , and selective ( COX 2 SI = 81 ) , COX 2 inhibitor which is a potent AI agent ( ID ( 50 ) = 4 . 1mg / kg ) with equipotent analgesic activity to celecoxib . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Stromal immunostaining for COX 1 as well as COX 2 was increased in the TP and PP groups as compared to the NP , and GE displayed an intensely increased COX 2 immunostaining at term and postpartum . ^^^ Concomitantly there is an increase of factors such as NFkappaB , PAF R , COX 1 and COX 2 , suggesting that they may participate in the sequence of events leading to the final cervical ripening . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of the two different cyclo oxygenases ( COX 1 and COX 2 ) led to the incorporation of more selective enzyme inhibitors into the therapeutic tools against disorders with pain and inflammation , in order to minimize the frequency of the side effects . ^^^ Conclusions : Non selective NSAIDs show a mixed effect of inhibitions of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The galactosyl diacylglycerols 1 3 inhibited the cyclooxygenase 1 ( COX 1 ) enzyme by 78 , 63 , and 93 % and the cyclooxygenase 2 ( COX 2 ) enzyme by 87 , 74 , and 95 % , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro COX 1 and COX 2 isozyme inhibition structure activity studies identified ( Z ) 1 , 2 diphenyl 1 ( 4 methanesulfonylphenyl ) oct 1 ene ( 7d ) as a potent COX 2 inhibitor ( IC ( 50 ) = 0 . 42 microM ) with a high COX 2 selectivity index ( SI > 234 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The respiratory chain genes ( nad 7 , cox 1 , cox 2 , atp 6 ) showed mRNA profiles which paralleled those of the ribosomal RNAs , whereas ribosomal protein genes ( rps 2 , rps 3 , rps 7 ) had proportionately lower steady state mRNA levels in later stages of seedling development . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : The purpose of this study was to determine which COX isoform , COX 1 or COX 2 , is responsible for regulating the protective surface pH gradient and to test if COX inhibitors also had non COX mediated effects in vivo . ^^^ We used in vivo confocal microscopy to measure pH near the mucosal surface of anaesthetised COX 1 ( / ) , COX 2 ( / ) , or wild type mice of the same genetic background . ^^^ RESULTS : When the gastric mucosal surface was exposed and superfused ( 0 . 2 ml / min ) with a weakly buffered saline solution ( pH 3 ) containing the pH indicator Cl NERF , the pH directly at the gastric surface and thickness of the pH gradient were similar in wild type and COX 2 ( / ) mice , but COX 1 ( / ) mice had a significantly thinner pH gradient . ^^^ Addition of indomethacin had minimal effects on the residual surface pH gradient in COX 1 ( / ) mice , suggesting no role for COX 2 in surface pH regulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our data establish a role for COX 1 and COX 2 in facilitating the efficient growth and replication of PRV in primary cells . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two principal cyclooxygenase isoforms referred to as COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We researched the expression of COXs ( COX 1 and COX 2 ) and LOXs ( 5 LOX and 12 LOX ) in rat renal I / R injury . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we demonstrate that PGJ 2 enhances COX 2 gene expression without elevating COX 1 levels in neuronal cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenase enzymes ( COX 1 , COX 2 , and COX 3 ) convert arachidonic acid to prostaglandins , prostacyclins , thromboxanes , and other hydroxy fatty acids . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The compounds were evaluated for their ability to inhibit cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) activity in human whole blood ( HWB ) . ^^^ The compound , 5 ( 4 methanesulfonylphenyl ) 3 ( 2 methoxytetrahydrofuran 2 yl ) 1 p tolyl 1H pyrazole 5 showed potent and selective COX 2 inhibition ( IC 50 for COX 1 : > 100 microM and COX 2 : 1 . 2 microM ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated whether cyclooxygenase ( COX ) isoforms ( COX 1 and COX 2 ) and decreased NO availability contribute to endothelial dysfunction in endotoxemic rats . ^^^ In LPS treated rats , reverse transcription polymerase chain reaction showed a marked increase in mesenteric iNOS and COX 2 expressions , whereas endothelial nitric oxide synthase and COX 1 were unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 protein levels were not significantly increased in cirrhotic livers , but COX 2 protein expression was increased . ^^^ COX 1 inhibition , but not COX 2 , significantly attenuated the response to Mtx and prevented the increased production of TXA ( 2 ) . ^^^ Despite abundant hepatic COX 2 expression , the increased response to Mtx of cirrhotic livers is mainly dependent of COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nociception and the differential expression of cyclooxygenase 1 ( COX 1 ) , the COX 1 variant retaining intron 1 ( COX 1v ) , and COX 2 in mouse dorsal root ganglia ( DRG ) . ^^^ Our results demonstrated that COX 1 ( and not COX 2 ) was the primary isoform involved in nociception in both model systems . ^^^ We found that COX 1 and COX 1v were both expressed in neurons while COX 2 expression was completely undetectable in the DRG . ^^^ Immunohistochemical analysis of COX expression in DRG of mice exhibiting the chronic pain and inflammation associated with collagen induced arthritis ( CIA ) expressed COX 1 and COX 1v while no COX 2 could be detected . ^^^ Together , these data support a role for COX 1 and perhaps COX 1v , not COX 2 , as the primary producers of PGs in mouse DRG in normal and in mice subject to chronic pain and inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Skin blood flow ( SkBF ) variations induced by 5 min of 0 . 1 mA monopolar anodal current application were evaluated with laser Doppler flowmetry on the forearm of healthy volunteers treated with indomethacin ( COX 1 and COX 2 inhibitor ) , celecoxib ( COX 2 inhibitor ) , or placebo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synovitis in horses is frequently treated by administration of non steroidal anti inflammatory drugs ( NSAIDs ) , which inhibit cyclooxygenase isoforms ( COX 1 and COX 2 ) . ^^^ Constitutively expressed COX 1 is involved in physiologic functions such as maintenance of gastric mucosal integrity , whereas COX 2 is up regulated at sites of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Significant synergism of Cox 1 and Cox 2 inhibitors was observed in both bladder cancer lines at both 24 and 72 hours . ^^^ CONCLUSIONS : Significant synergistic effects exhibited by the combination of Cox 1 and Cox 2 inhibitors suggest that these could become a highly effective treatment modality for carcinoma of both the bladder and prostate . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Rofecoxib is the most specific COX 2 inhibitor among the first generation of the class , i . e . , negligible COX 1 inhibitory effect . ^^^ It is plausible that the COX 2 inhibition is associated with altered homeostasis that is compensated with the cardioprotection effect of COX 1 inhibition that patients receive either through the less COX 2 selectivity of other NSAIDs or through co administration of low dose aspirin . ^^^ However , based on some available indirect evidence , and unless more clear cut data become available , the use of highly COX 2 selective NSAIDs without the use of a suitable COX 1 inhibitor , ( e . g . , low dose aspirin ) may be best avoided . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In conclusion , COX 2 , but not COX 1 , plays a significant role in mechanical stimulus induced peritoneal formation in the mouse cecum . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Zebrafish cytosolic ( c ) PGES 1 and COX 1 were coordinately expressed ; mPGES 1 and COX 2 were expressed particularly in the vasculature . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , was a breakthrough that led to obtaining the so called coxibs , which selectively inhibit COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of the two isoenzymes COX 1 and COX 2 and the knowledge of their function , localisation and regulation has initiated the development of COX 2 selective inhibitors ( coxibs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The 2 ' des methyl analogue of INDO ( DM INDO ) was synthesized and tested against wild type COX 1 and COX 2 , as well as the Val 349 mutants . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of LPS on cortisol were attenuated in the presence of both indomethacin and a specific COX 2 inhibitor , but not a COX 1 inhibitor , suggesting an obligatory role for COX 2 activation and prostaglandin synthesis in the adrenal response to LPS . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : The colorectal neoplasms were induced with DMH in mice and the different dose of CHL were administered in different phases , then the prevention of colorectal neoplasms by CHL was examined ; The IC 50 and growth curve of HT 29 cells were measured with MTT method after treated with CHL ; The effect of CHL on the expression of COX 1 mRNA and COX 2 mRNA in HT 29 cells were measured with RT PCR method ; The effect of CHL on the expression of COX 2 protein and NF kappaB protein were measured with western blot and immunohistochemistry methods . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is a potent peroxidase dependent mechanism based inactivator of COX 1 , a desired target for antiplatelet agents , and has no similar effect on COX 2 . ^^^ In this study we show that other red wine constituents , namely , the catechins ( 2 , 3 ) and epicatechins ( 4 , 5 ) , act as peroxidase mediated mechanism based inactivators of COX 1 but not of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the eye , cholesterol diet attenuated the positive effects of fish oil on inflammatory gene expression as the combined diet resulted in increased RNAm level of phospholipase A 2 , inducible nitric oxide synthase , TNF alpha , COX 1 , COX 2 and cytokine , ICAM 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Our results show that thalidomide and IMiDs inhibited the expression of COX 2 but not the COX 1 protein in LPS TNF alpha and IL 1beta stimulated PBMC and shortened the half life of COX 2 mRNA in a dose dependent manner . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To further investigate the interaction between upstream and downstream enzymes involved in brain prostaglandin synthesis , we examined expression and activity of COX 1 , of different PLA 2 enzymes and of prostaglandin E synthase ( PGES ) enzymes in COX 2 ( / ) mice . ^^^ However , when we supplied exogenous arachidonic acid ( AA ) to brain homogenates , COX activity was increased in the COX 2 ( / ) mice , suggesting a compensatory activation of COX 1 and an intracellular compartmentalization of the COX isozymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( Cox 2 ) is implicated in the pathogenesis of many cancers including esophageal adenocarcinoma ( EAC ) , whereas the role of the isoform Cox 1 in carcinogenesis is not well understood . ^^^ To further elucidate the role of these factors in the development of EAC , we measured the gene expressions ( mRNA levels ) of Cox 2 and Cox 1 by real time quantitative polymerase chain reaction ( QRT PCR ) in tissues from normal esophagus with and without erosive gastroesophageal reflux disease ( GERD ) , Barrett ' s esophagus ( BE ) , dysplasia , adenocarcinoma , and in healthy gastric antrum . ^^^ In contrast to that of Cox 2 , Cox 1 expression was significantly decreased in all neoplastic tissues compared to normal controls . ^^^ Cox 1 and Cox 2 expression varied over a wide range in the neoplastic tissues but over a relatively narrow range in the esophageal normal tissues . ^^^ The occurrence of substantial alterations in Cox 1 and Cox 2 expression at the BE stage indicates that these are early events in the development of EAC . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Both COX 1 and COX 2 are expressed in the kidney . ^^^ This was temporally associated with increased renal COX 2 protein expression and increased urinary PGE ( 2 ) excretion , whereas COX 1 levels remained unchanged . ^^^ COX 2 inhibition completely prevented polyuria and PGE ( 2 ) excretion in COX 1 / mice , suggesting that COX 2 , but not COX 1 , plays a critical role in lithium induced polyuria . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Blood and kidney samples were collected at reperfusion times . mRNA was extracted from the kidney samples to amplify COX 1 , COX 2 and beta actin genes . ^^^ Blockade of COX 1 and 2 resulted in a decrease of tubular necrosis . mRNA COX 2 was up regulated post IRI and considerable inhibited after indomethacin or rofecoxib treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Following on from previous studies on dermal inflammation in the isolated perfused bovine udder , a new in vitro model of the isolated haemoperfused bovine uterus was established for studies on acute inflammatory reactions ( for example , eicosanoid synthesis and regulation of cyclooxygenase 1 [ COX 1 ] and COX 2 ) caused by ischaemia reperfusion ( 1 R ) injury . ^^^ In addition , the regulation of COX 1 and COX 2 mRNA was investigated by using the reverse transcriptase polymerase chain reaction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction ( RT PCR ) verified expression of COX 2 in colonic muscles , and quantitative PCR demonstrated that COX 1 transcriptional expression was greater than COX 2 . ^^^ To test the functional significance of COX 2 expression , the effects of a COX 2 inhibitor were compared with the effects of indomethacin ( COX 1 / COX 2 inhibitor ) on circular muscle contractions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Whole blood in vitro assays are used to investigate quantitatively the three key PD parameters ( efficacy , potency and sensitivity ) for NSAID inhibition of COX isoforms , providing data on COX 1 : COX 2 inhibition ratios . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Examples are provided of the generation of PD parameters for several NSAIDs ( carprofen , ketoprofen , vedaprofen , flunixin and tolfenamic acid ) in species of veterinary interest ( horse , calf , sheep and goat ) , which indicate that all drugs investigated except vedaprofen were non selective for COX 1 and COX 2 in the four species investigated under the experimental conditions used , vedaprofen being a COX 1 selective NSAID . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two cyclooxygenase isoforms ( COX 1 and COX 2 coxibs ) have overlapping functions and both are involved in the regulation of homeostatic and inflammatory processes in the various tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Various regression equations were derived to study the influence of phenoxy and phenyl ring substituents of series 1 compounds on COX 2 , COX 1 and selective COX 2 over COX 1 inhibitory activity . ^^^ QSAR model derived to explore the selective COX 2 over COX 1 inhibition showed that selectivity could be influenced by size and lipophilicity of substituents . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The intestinal hypermotility caused by COX 1 inhibition may be a key to COX 2 expression after administration of NSAIDs and their intestinal ulcerogenic properties . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of mRNA for both COX 1 and 2 in the lung was evaluated 4 h after the intratracheal administration . 15d PG J 2 enhanced the COX 2 mRNA expression in the presence of LPS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The muscarinic agent carbachol induced HPA response was considerably supressed by piroxicam , a predominantly constitutive cyclooxygenase ( COX 1 ) inhibitor and significantly diminished by indomethacin , a non selective COX blocker , but was unaffected by compound NS 398 , an inducible cyclooxygenase ( COX 2 ) antagonist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunostaining showed that uninjured vessel segments stained positive only for COX 1 but not for COX 2 . ^^^ Injured vessel segments showed , in addition to COX 1 , significant positive staining for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The in vitro pharmacological evaluation of the synthesized compounds against COX 1 and COX 2 was performed in a human whole blood model . ^^^ Results obtained demonstrated that most of alkanesulfonamide derivatives displayed a COX 2 preferential inhibition with selectivity ratio values ( IC ( 50 ) ( COX 1 ) / IC ( 50 ) ( COX 2 ) ) up to 7 . 92 ( celecoxib displaying a ratio value of 7 . 46 in the same test ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LPS stimulation increased the expression of COX 2 but not COX 1 or COX 3 . ^^^ Our results show that prostaglandin production in CECs during basal and stimulated conditions is very sensitive to inhibition by acetaminophen and suggest that acetaminophen acts against COX 2 and not COX 1 or COX 3 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It encodes , all on the same DNA strand , three subunits of cytochrome oxidase ( COX 1 , COX 2 and COX 3 ) , three subunits of ATP synthetase ( ATP 6 , ATP 8 and ATP 9 ) , the apocytochrome b ( COB ) , the ribosomal protein VAR 1 , 24 tRNAs , the small and large ribosomal RNAs , and the RNA subunit of RNase P . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : Tissue samples of primary and secondary tumors from 288 patients undergoing surgical resections for colorectal adenocarcinoma were immunohistochemically examined for Cox 2 and Cox 1 expressions . ^^^ The specimens were graded based on the intensity and extent of staining ; then , the correlations between Cox 2 and Cox 1 expressions with clinicopathologic parameters and survival time were analyzed . ^^^ CONCLUSIONS : Elevated Cox 2 expression , but not that of Cox 1 , was significantly associated with reduced survival and recognized as an independent prognostic factor in our cohort of colorectal cancer patients . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is better expressed than COX 2 , particularly in the premature , but COX 2 is more extensively coupled with microsomal PGES ( mPGES ) . ^^^ Furthermore , when studied separately , COX 1 and COX 2 prove to be unevenly responsive to indomethacin , and an immediate and fast developing contraction of the vessel occurs only when COX 2 is inhibited . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This hypothermic effect of paracetamol was reduced in COX 1 but not in COX 2 gene deleted mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Under resting conditions , RMC expressed COX 1 , COX 2 and 12 / 15 lipoxygenase and mainly generated prostaglandin ( PG ) E 2 , thromboxane ( TX ) B 2 , 12 hydroxyeicosatetraenoic acid ( 12 HETE ) and 8 epi PGF2alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 mRNA in laminae of control and affected horses was evaluated via real time quantitative polymerase chain reaction techniques . ^^^ In contrast to COX 2 regulation , COX 1 mRNA expression was not significantly different between groups . ^^^ CONCLUSIONS AND CLINICAL RELEVANCE : Results indicated that there was a significant upregulation of COX 2 mRNA expression during the developmental stages of laminitis , with no significant change in expression of the COX 1 isoform . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibitor combination caused injury in vivo and in vitro but did not decrease survivin expression . ^^^ CONCLUSIONS : ( 1 ) Indomethacin , but not selective COX 1 or COX 2 inhibitors alone or in combination , reduces survivin expression in gastric mucosal cells and ( 2 ) significant reduction of survivin precedes greater severity of gastric injury . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pregnancy induced changes in Cox 1 , Cox 2 and NOSIII vascular and renal expression . ^^^ In order to establish if there is a mutual regulation between COX and NOS in vascular and renal tissue during pregnancy , we measured the protein expression of COX 1 , COX 2 and NOSIII by Western blot comparing the thoracic and abdominal aorta and the renal cortex and medulla of non pregnant and pregnant ( 21st day ) Wistar rats . ^^^ We found there was no difference in the quantity of protein of any of the two isoforms of COX between the two segments of the aorta of non pregnant animals while an increased expression of both COX 1 And COX 2 was found in the abdominal compared to the thoracic segment of the pregnant rats . ^^^ No changes were found between pregnant and no pregnant animals in the expression of COX 1 and COX 2 in the renal cortex or medulla while an increased expression of NOS 3 was found in the cortex from pregnant compared to non pregnant animals . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : Two isoforms of cyclooxygenase ( COX 1 and COX 2 ) exist . ^^^ To determine in vivo effects of the intravenous administration of FR 122047 ( a selective COX 1 inhibitor ) , FR 188582 ( a selective COX 2 inhibitor ) , diclofenac sodium or dexamethasone phosphate disodium on prostaglandin E 2 ( PGE 2 ) induced aqueous flare elevation and mRNA levels for COX 1 and COX 2 in pigmented rabbits . ^^^ The mRNA levels for COX 1 and COX 2 in the iris ciliary body were determined by real time polymerase chain reaction . ^^^ Less than 3 fold changes in mRNA levels for COX 1 and COX 2 in the iris ciliary body were noted after PGE 2 , FR 122047 , FR 188582 , diclofenac sodium or dexamethasone phosphate disodium treatment . ^^^ CONCLUSION : It is possible that enzyme activities of both COX 1 and COX 2 may be involved in the mechanism of PGE 2 induced aqueous flare elevation in pigmented rabbits . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Altered expression of COX 1 , COX 2 , and mPGES in rats with nephrogenic and central diabetes insipidus . ^^^ We hypothesize that the expression of the major PGE 2 synthesis enzymes cyclooxygenases 1 and 2 ( COX 1 , COX 2 ) and membrane associated PGE 2 synthase ( mPGES ) is altered in the kidneys of rats with NDI and CDI . ^^^ Expression and localization of COX 1 , COX 2 , and mPGES in IM , inner stripe of outer medulla ( ISOM ) , and cortex were determined by immunoblotting and immunohistochemistry . ^^^ In lithium induced NDI , expression of COX 1 , COX 2 , and mPGES was markedly decreased in IM . ^^^ Dehydration of NDI rats resulted in a marked increase in COX 2 immunolabeling in IM interstitial cells , and there was no significant change in COX 1 and mPGES expression in any kidney zone . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclo oxygenase ( COX ) 2 specific inhibitors , which have an improved safety profile compared to traditional NSAIDs that inhibit both the COX 1 and COX 2 enzymes , seem to be well suited drug candidates for CRC prevention . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of NADPH oxidase subunits , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) , nuclear transcription factor NF ( kappa ) B ( NF kappaB ) p 65 subunit , Ikappa B ( IkappaB ) , and phospho Ikappa B ( phospho IkappaB ) was evaluated by Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Because this protein has a completely different amino acid sequence than COX 1 and COX 2 and it does not have cyclooxygenase activity , we suggest a name cyclooxygenase variant protein to distinguish it from the known prostaglandin synthesizing cyclooxygenase isoforms . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase ( COX 1 and COX 2 ) and human lipoxygenase ( 5 LOX ) inhibitors . ^^^ A new series of potential human 5 LOX inhibitors structurally related to the 1 phenyl 3 pyrazolidinone ( phenidone , 2 ) has been synthesized and the activity against COX 1 , COX 2 , and human 5 LOX enzymes has been evaluated . ^^^ The present results suggest that the substitution of the amino function at the 4 position is detrimental in terms of activity toward COX 1 and COX 2 , while the presence of a double bond at the 4 , 5 position does not alter the biological profile against COX . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To identify the distribution of the enzymes cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) , and cytosolic phospholipase A ( 2 ) ( cPLA ( 2 ) ) in the human ovary and endometrium . ^^^ MAIN OUTCOME MEASURE ( S ) : Pinopode formation and immunohistochemical staining of cPLA ( 2 ) , COX 1 , and COX 2 . ^^^ The staining of both COX 1 and COX 2 was most intense in the epithelial cells , with the stroma staining positive only for COX 2 . ^^^ The endometrial vessels expressed COX 2 but not COX 1 . ^^^ The staining of COX 1 and COX 2 was intense on the surface epithelial cells on the outer lining of the ovary . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Semiquantitative reverse transcription polymerase chain reaction was used to assess the mRNA expression of MMP 1 to 13 , COX 1 and COX 2 . ^^^ In contrast , COX 1 was slightly upregulated and COX 2 tended to be downregulated by Geho resulting in a decreased PGE 2 concentration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although inhibition or deletion of COX 1 retards atherogenesis in ApoE and LDL receptor ( LDLR ) KOs , the role of COX 2 in atherogenesis remains controversial . ^^^ METHODS AND RESULTS : TP antagonism with S 18886 , but not combined inhibition of COX 1 and COX 2 with indomethacin or selective inhibition of COX 2 with Merck Frosst ( MF ) tricyclic , retards significantly atherogenesis in DKOs . ^^^ CONCLUSIONS : TP antagonism is more effective than combined inhibition of COX 1 and COX 2 in retarding atherogenesis in Apobec 1 / LDLR DKO mice , which perhaps reflects activation of the receptor by multiple ligands during disease initiation and early progression . ^^^ TP ligands , including COX 1 ( but not COX 2 ) derived TxA 2 , promote initiation and early progression of atherogenesis in Apobec 1 / LDLR DKOs but appear unimportant in the maintenance of established disease . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Lumiracoxib inhibited purified COX 1 and COX 2 with K ( 1 ) values of 3 and 0 . 06 microM , respectively . ^^^ In cellular assays , lumiracoxib had an IC ( 50 ) of 0 . 14 microM in COX 2 expressing dermal fibroblasts , but caused no inhibition of COX 1 at concentrations up to 30 microM ( HEK 293 cells transfected with human COX 1 ) . 3 . ^^^ In a human whole blood assay , IC ( 50 ) values for lumiracoxib were 0 . 13 microM for COX 2 and 67 microM for COX 1 ( COX 1 / COX 2 selectivity ratio 515 ) . 4 . ^^^ Ex vivo , lumiracoxib inhibited COX 1 derived thromboxane B ( 2 ) ( TxB ( 2 ) ) generation with an ID ( 50 ) of 33 mg kg ( 1 ) , whereas COX 2 derived production of prostaglandin E ( 2 ) ( PGE ( 2 ) ) in the lipopolysaccharide stimulated rat air pouch was inhibited with an ID ( 50 ) value of 0 . 24 mg kg ( 1 ) . 6 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study investigates the effects of gastrin 17 on human colon cancer HT 29 cells to examine whether gastrin receptor ( CCK 2 ) , cyclooxygenase ( COX 1 , COX 2 ) isoforms and prostaglandin receptor pathways interact to control cell growth . ^^^ Reverse transcription ( RT ) polymerase chain reaction ( PCR ) analysis demonstrated that HT 29 cells are endowed with the naive expression of CCK 2 receptor ( short splice variant ) , COX 1 , COX 2 and prostaglandin EP ( 4 ) receptor , but not gastrin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Interestingly , the most antitumor active compounds were potent COX inhibitors ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Paracetamol is a weak inhibitor of PG synthesis of COX 1 and COX 2 in broken cell systems , but , by contrast , therapeutic concentrations of paracetamol inhibit PG synthesis in intact cells in vitro when the levels of the substrate arachidonic acid are low ( less than about 5 mumol / L ) . ^^^ When the levels of arachidonic acid are low , PGs are synthesized largely by COX 2 in cells that contain both COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 protein and activity were also increased after exposure to 2 , 2 ' , 4 , 4 ' tetrachlorobiphenyl ; COX 1 protein and activity were unaffected . 3 , 3 ' , 4 , 4 ' Tetrachlorobiphenyl did not increase COX 2 mRNA levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIM : to know the effect of piroxicam ( COX 1 and COX 2 inhibitor NSAID ) and meloxicam ( selective COX 2 inhibitor NSAID ) against the gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Pure petasin and isopetasin neither inhibited COX 1 nor COX 2 ( IC 50 > 400 microM for both compounds and enzymes ) . ^^^ COX 2 synthesis in microglia was totally blocked with 5 microg / mL of C whereas COX 1 synthesis was not influenced . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Many individuals use cyclo oxygenase inhibitors ( COX 1 and COX 2 non steroidal anti inflammatory drugs ) and antiplatelet medications on a regular basis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Lanostane triterpenoids and triterpene glycosides from the fruit body of Fomitopsis pinicola and their inhibitory activity against COX 1 and COX 2 . ^^^ Their structures were established primarily by NMR experiments and chemical methods , and their biological activity against COX 1 and COX 2 was investigated . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Anti inflammatory strategies in hypertension : focus on COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The m cresol ( 2 and 5 mM ) inhibited the COX 1 activity by 55 99 % , but showed little effect on COX 2 enzyme activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This SSG reduced nitric oxide ( NO ) and prostaglanin E 2 ( PGE 2 ) production in mouse peritoneal macrophages stimulated with lipopolysaccharide , without the influence on the activity of inducible NO synthase ( iNOS ) , cyclooxygenase COX 2 and COX 1 being observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
More specifically , the overexpression of COX 1 , COX 2 , MMP 2 , and MMP 9 in gingival tissues suggests that they are involved in PAR 2 induced periodontitis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , little is known about the rate limiting enzymes of prostaglandin synthesis in the inner ear , the generally constitutively expressed cyclooxygenase 1 ( COX 1 ) and the distress inducible cyclooxygenase 2 ( COX 2 ) . ^^^ Both COX 1 and COX 2 immunoreactions were also found in the spiral ganglion . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of nonsteroidal antiinflammatory drugs , COX 1 and COX 2 selective inhibitors on aromatase activity and expression were studied in human breast cancer cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND / AIMS : Water diuresis usually increases medullary oxygenation as a result of increased medullary synthesis of prostaglandins , but it is not clear whether this involves activation of cyclooxygenase 1 ( COX 1 ) or cyclooxygenase 2 ( COX 2 ) . ^^^ METHODS : The effects of celecoxib , a selective inhibitor of COX 2 , and of ibuprofen , a non specific inhibitor of COX 1 and COX 2 , upon renal oxygenation during water diuresis were studied in a double blind , prospective manner in 13 young women ( age 24 34 years ) using blood oxygen level dependent magnetic resonance imaging . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Transfection of iPLA2gamma into HCA 7 cells also led to increased AA release and prostaglandin E 2 synthesis via both COX 1 and COX 2 , with a concomitant increase in cell growth . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Most nonsteroidal anti inflammatory drugs ( NSAIDs ) are non selective cyclooxygenase 1 ( COX 1 ) and COX 2 inhibitors and are associated with upper gastrointestinal ( GI ) dyspeptic symptoms often resulting in GI co medication usage or treatment discontinuation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The rsm 28 null mutation also reduced translation of an ARG8m reporter sequence inserted at the COX 1 , COX 2 , and COX 3 mitochondrial loci . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The non steroidal anti inflammatory drugs ( NSAID ) block the activity of both COX 1 and COX 2 , whereas the selective inhibitors of COX 2 ( the coxibs ) act only on this isoform . ^^^ Actually , the therapeutic effects of both NSAIDs and coxibs are due to their actions on COX 2 , while the system toxicity of NSAIDs ( gastrointestinal perforation or ulcer , reduction of glomerular filtration rate , prolongation of bleeding time ) is ascribable to the inference of these drugs with the COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These include all the phospholipases A 2 ( PLA 2 ) that we detected in P388D1 cells , cyclooxygenases ( COX ) , COX 1 and COX 2 , the membrane associated prostaglandin E synthase 1 ( mPGES 1 ) , the lipocalin type prostaglandin D 2 synthase ( PGDS ) , hematopoietic PGDS and the subunit G ( alpha i 2 ) of heterotrimeric G proteins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective inhibitors of COX 1 [ 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethyl pyrazole ( SC 560 ) ] , COX 2 [ N [ 2 ( cyclohexyloxy ) 4 nitrophenyl ] methanesulfonamide ( NS 398 ) , rofecoxib ] , or COX 3 ( antipyrine ) or a nonselective inhibitor of the COX 1 / 2 isoforms ( ketoprofen ) did not protect mice from neurotoxicity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 inhibition had no effect on blood pressure in either control or experimental animals . 11betaHSD2 inhibition also led to medullary COX 2 increase and cortical COX 2 decrease in weaning rats , primarily through activation of MRs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Additionally , brain protein levels of COX 1 , COX 2 , 5 lipoxygenase , and cytochrome P 450 epoxygenase were unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , cPLA 2 alpha was seen to partially colocalize specifically with the COX 2 isoform at the ER resembling structures , but not with COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : To test the hypothesis that both COX 1 and COX 2 expression in human gastric mucosa is up regulated in the presence of inflammation as seen in patients with gastritis and gastric ulcers . ^^^ METHODS AND RESULTS : We performed immunohistochemistry using COX 1 and COX 2 monoclonal antibodies on gastric biopsies from 59 patients with normal mucosa , gastritis and gastric ulcers . ^^^ Expression of COX 1 and COX 2 was quantified using an intensity proportion scoring system . ^^^ We found a stepwise increase in the expression of both COX 1 and COX 2 as mucosal damage progressed from normal to gastritis to gastric ulcer . ^^^ CONCLUSIONS : We conclude that both COX 1 and COX 2 expression in the gastric mucosa are increased in the setting of gastritis and gastric ulceration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this model TA was a nonselective inhibitor of cyclo oxygenase ( COX ) ( COX 1 : COX 2 IC 50 ratio = 1 . 37 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LPS treated RAW produced PGs more slowly and reached their maximal PG synthetic rate later than did LPS treated RPMs , as a result of lower constitutive COX 1 expression and a slower rate of COX 2 induction . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , the stimulation of isolated rat hepatocytes with CT 1 increased COX 1 , COX 2 , and VEGF messenger RNAs and prostaglandin synthesis . ^^^ CT 1 can restore liver regeneration after COX 2 inhibition by increasing VEGF , COX 1 expression , and prostaglandin synthesis . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , the expression of metalloproteases ( MMP 1 and MMP 9 ) and cyclooxygenases ( COX 1 and COX 2 ) in the bursitis group was found to be increased as compared with controls . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When tested for inhibitory activity , five compounds ( 2 , 3 , 7 , 10 and 13 ) showed preferential inhibition of COX 2 over COX 1 , while compounds 4 , 5 and 8 lacked inhibitory effect on either the COX 1 or COX 2 isozyme . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAIDs ) are widely used for the treatment of inflammatory diseases and target cyclooxygenases 1 and 2 ( Cox 1 , Cox 2 ) that are responsible for PG production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : Our results support the hypothesis that progesterone and MPA increased HUVEC prostacyclin production in a progesterone receptor dependent manner , by enhancing COX 1 and COX 2 expression and activities . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While the bradykinin B 1 antagonist des Arg 10 HOE 140 , the selective COX 1 inhibitor SC 560 , and the selective COX 2 inhibitor celecoxib did not affect post operative pain , the B 2 antagonist HOE 140 dose dependently relieved the post operative pain at 2 200 microg / kg with a time course similar to that of zaltoprofen . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These compounds were tested with COX 1 and COX 2 inhibition assays . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin significantly reduced the contractile response of both segments of the aorta , whereas expression of COX 1 , COX 2 and eNOS were increased only in the abdominal segment of pregnant animals . 4 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Labeling indices ( LIs ) for COX 1 , COX 2 , Ki 67 and P 53 , microvessel density ( MVD ) and apoptotic index ( AI ) were evaluated using immunohistochemistry and TUNEL methods . ^^^ LIs of COX 2 but not COX 1 correlated with the histological grade of dysplasia , being highest for the severe dysplasias ( p < 0 . 05 ) . ^^^ In contrast , the COX 2 LIs as well as COX 1 were significantly ( p < 0 . 05 ) inversely correlated with the histological differentiation of the SCCs . ^^^ COX 2 expression was significantly correlated with LIs of COX 1 for dysplasia ( p < 0 . 05 ) , but not for the SCCs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Real time RT PCR showed COX 2 ( / ) mice to express significantly greater COX 1 expression in loaded ulnas than in loaded ulnas in COX 2 ( + / + ) mice . ^^^ Investigating a potential reason for the absence of a genotype difference in this study , we found that mice with a null mutation in the COX 2 gene possess inductive skeletal COX 1 expression . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases ( Cox ) 1 and 2 play important roles in gastrointestinal health ; chronic overexpression of Cox 2 is associated with inflammatory and cancerous disease , whereas Cox 1 is expressed constitutively . ^^^ Butyrate , which is anticarcinogenic , resulted in an 85 % down regulation of Cox 2 and a 37 fold increase in Cox 1 transcription . ^^^ Propionate gave similar results ( 72 % reduction of Cox 2 , 23 fold induction of Cox 1 ) , but lactate and acetate had no effect on Cox expression profile . ^^^ Bifidobacterium sp . 420 , which produces acetate and lactate but no butyrate or propionate , shared the Cox 1 increasing and Cox 2 silencing properties of butyrate and propionate , whereas L . acidophilus was similar to E . coli and S . enteritidis in having no effect on the Cox 1 / Cox 2 ratio . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro COX 1 / COX 2 inhibition studies showed that 11 is a more potent inhibitor ( COX 1 IC ( 50 ) =0 . 06microM ; COX 2 IC ( 50 ) =0 . 25microM ) than aspirin ( COX 1 IC ( 50 ) =0 . 35microM ; COX 2 IC ( 50 ) =2 . 4microM ) , and like aspirin [ COX 2 selectivity index ( S . ^^^ I . > 1149 ) , or C 5 ( COX 2 IC ( 50 ) =0 . 77microM , SI > 130 ) , position of 11 exhibited the most potent and selective COX 2 inhibitory activity relative to the reference drug celecoxib ( COX 1 IC ( 50 ) =33 . 1microM ; COX 2 IC ( 50 ) =0 . 07microM ; COX 2 S . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of prostaglandin synthesis in cell microsomal fractions was first evaluated , followed by screening for specific inhibition of isolated cyclooxygenase enzymes ( COX 1 and COX 2 ) . ^^^ Only one compound exhibited a high level of anti inflammatory activity in the COX 1 enzyme assay and no significant activity was detected in the COX 2 enzyme assay . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : COX 1 but not COX 2 was detected in PC 3 and LNCaP cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effect of nonsteroidal anti inflammatory drugs with varying extent of COX 2 COX 1 selectivity on urinary sodium and potassium excretion in the rat . ^^^ Nonsteroidal anti inflammatory drugs ( NSAIDs ) have different selectivity to inhibit cyclooxygenase 1 ( COX 1 ) and COX 2 . ^^^ We compared the effect of a selected group of NSAIDs with different COX 2 COX 1 selectivities on urinary sodium and potassium excretion in rats . ^^^ At the examined dosage level , no relationship was found between reported COX 2 COX 1 selectivity and urinary electrolytes excretion . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast to LO , however , the cyclooxygenase ( COX ) may not be involved in the regulation of LPS mediated induction of iNOS gene because COX inhibition by indomethacin ( general COX inhibitor ) , SC 560 ( COX 1 inhibitor ) , and NS 398 ( COX 2 inhibitor ) affected neither the LPS induced iNOS expression nor activation of NFkappaB . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The methanesulfonyl regioisomers 13a , b [ COX 1 IC50=11 . 6 microM ; COX 2 IC50=0 . 12 microM ; COX 2 selectivity index ( SI ) =97 ] and aminosulfonyl regioisomers 16 ( COX 1 IC50=9 . 8 microM ; COX 2 IC50=0 . 78 microM ; COX 2 SI=12 ) , like the reference drug celecoxib ( COX 1 IC50=33 . 1 microM ; COX 2 IC50=0 . 07 microM ; COX 2 SI=472 ) , were potent in vitro COX 2 inhibitors with a good COX 2 selectivity index . ^^^ The in vitro NO release data , COX 1 / COX 2 inhibition and COX 2 SI structure activity relationships acquired , and molecular modeling docking studies suggest that the 1 , 2 , 5 oxadiazole 2 oxide ( furoxan ) ring possesses beneficial features that should be present in a suitable central ring template ( bioisostere ) pertinent to the design novel hybrid COX 2 inhibitor / nitric oxide donor agents with a low ulcerogenicity profile that may be free from adverse cardiovascular effects . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study focuses on development of new potential inhibitors of cyclooxygenase 2 ( COX 2 ) : series of N pyrrolylcarboxylic acids . 3D QSAR ( Quantitative Structure Activity Relationship ) CoMFA ( Comparative Molecular Field Analysis ) and CoMSIA ( Comparative Molecular Similarity Index Analysis ) models for predicting inhibitory activities against COX 1 and COX 2 as well as for evaluating in vivo anti inflammatory activity were obtained and used for preliminary screening of new anti inflammatory N pyrrolylcarboxylic acids . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression levels of FP receptor and cyclooxygenase ( COX 1 and COX 2 ) in the respective regions were also examined using RT PCR and Western blotting . ^^^ COX 1 but not COX 2 was detected in the non pregnant porcine uterus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This finding is discussed with respect to the differential expression of cyclooxygenase ( COX ) isoenzymes 1 and 2 ( COX 1 and COX 2 ) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls . ^^^ This finding is discussed with respect to the differential expression of cyclooxygenase ( COX ) isoenzymes 1 and 2 ( COX 1 and COX 2 ) in nasal polyps . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tissue sections were immunostained for COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Hypoxia induced release of PGD2 / PGJ2 was COX 1 dependent and did not involve COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After treatment with DMH and / or apple juices there were no changes in transcript levels of colonic cyclooxygenase isoforms ( COX 1 , COX 2 ) or glutathione associated enzymes ( GST M 2 , gamma GCS , GST P ) , the splenocyte natural killer cell activity and plasma antioxidant status . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Instead , we used DNA sequences comprising about 2300 bp derived from the mitochondrial genes COX 1 , COX 2 , and tRNA leucine to elucidate the phylogeny of Hyles . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The results reported herein address the questions of what factors are associated with expression ( relative messenger RNA levels ) of COX 1 and COX 2 in colorectal adenomas and whether there is heterogeneity in the protective effect of NSAIDs by levels of COX expression . ^^^ Results suggest that use of NSAIDs is associated with lower levels of COX 2 expression and that the protective effect of NSAIDs on polyp occurrence is stronger in the subgroup of cases with higher expression of COX 2 and a higher COX 2 / COX 1 ratio . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro anti inflammatory activity of Pinus sylvestris and Plantago lanceolata extracts : effect on inducible NOS , COX 1 , COX 2 and their products in J774A . 1 murine macrophages . ^^^ In this study , we investigated the effect of these plant extracts on the production of nitric oxide ( NO ) and prostaglandin E ( 2 ) , NO synthase ( NOS ) type 2 , cyclooxygenase 1 ( COX 1 ) and COX 2 mRNA expression in the murine macrophage cell line J774A . 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Thio rofecoxib , a selective COX 2 inhibitor ( 12 ) , is synthesized by this method and its IC ( 50 ) , microM COX 1 and COX 2 inhibition , and whole blood stability values reported . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As a part of our continuing efforts in discerning the structural and physicochemical requirements for selective COX 2 over COX 1 inhibition among the fused pyrazole ring systems , herein we report the QSAR analyses of the title compounds . ^^^ Balaban J , a connectivity topological index showed a negative and positive contribution towards COX 1 and selective COX 2 over COX 1 inhibition , respectively . ^^^ Wang Ford charges calculated on C ( 7 ) showed a significant contribution towards COX 1 inhibitory activity whereas charges calculated on C ( 8 ) were crucial in governing the selectivity of COX 2 over COX 1 inhibition among these congeners . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in most tissues , whereas COX 2 is induced in response to proinflamamatory cytokines and stress . ^^^ In this study we examined the expression of COX 1 and COX 2 in the rat after 90 minutes of warm I / R injury . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Carbachol stimulation of M ( 1 ) and M ( 3 ) mAChR exerts an increase in cox 1 mRNA gene expression without affecting cox 2 mRNA expression and increased PGE ( 2 ) generation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We did quantitative PCR of cytochrome c oxidase 1 ( Cox 1 ) and cytochrome c oxidase 2 ( Cox 2 ) genes on oral rinse samples obtained from 94 patients with primary head and neck squamous cell carcinoma ( HNSC ) and a control group of 656 subjects . ^^^ Mean levels of Cox 1 and Cox 2 in saliva samples were significantly higher in HNSC patients : Cox 1 , 0 . 076 [ 95 % confidence interval ( 95 % CI ) , 0 . 06 0 . 09 ] and Cox 2 , 0 . 055 ( 95 % CI , 0 . 04 0 . 07 ) in comparison with controls Cox 1 , 0 . 054 ( 95 % CI , 0 . 05 0 . 06 ) , P < 0 . 0001 and Cox 2 , 0 . 046 ( 95 % CI , 0 . 04 0 . 05 ) , P = 0 . 003 ( t test ) . ^^^ MtDNA levels were elevated in primary tumors when compared with matched , pretreatment saliva and significant correlation was noted ( Cox 1 , r = 0 . 30 , P = 0 . 005 and Cox 2 r = 0 . 33 , P = 0 . 002 , respectively , Pearson ' s correlation ) . ^^^ Multivariate analysis showed a significant and independent association of HNSC diagnosis , age , and smoking with increasing mtDNA / nuclear DNA for Cox 1 and Cox 2 . mtDNA content alteration is associated with HNSC independently of age and smoking exposure , can be detected in saliva , and may be due to elevation in mtDNA content in primary HNSC . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The results revealed that , while Cox 1 ( also known as Ptgs 1 ) mRNA levels were similar , Cox 2 mRNA levels were lower in uterus of null animals than in wild type siblings . ^^^ Treating the wild type uterine cells with hCG resulted in a Cox 2 but not Cox 1 mRNA increase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : Fifteen tumour cell lines were characterized for COX 1 and COX 2 expression by Western blot and RT PCR . ^^^ RESULTS : COX 2 expression varied among cell lines , whereas COX 1 was always expressed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX enzymes ( COX 1 and COX 2 ) are key enzymes of prostaglandin ( PG ) biosynthesis and are overexpressed in approximately 80 % of human CRCs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the levels of COX 1 , COX 2 , and prostaglandin ( PG ) E ( 2 ) in human fibroblasts isolated from normal peritoneal and adhesion tissues . ^^^ MAIN OUTCOME MEASURE ( S ) : We used Western blot to determine the effects of hypoxia on COX 1 and COX 2 levels from lysates of normal peritoneal and adhesion fibroblasts before and after hypoxia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 were inhibited to different extent by ethanol extracts from Triptergium wilfordii Hook . ^^^ CONCLUSIONS : Part of anti rheumatic mechanism of the two herbs might probably be mediating through inhibition of lymphocyte proliferation , COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Like cox 2 and rnl , cox 1 and cox 3 are not separated by tRNA genes ; instead , transcription initiation from the promoters upstream from rnl and cox 3 compensates for the lack of tRNA mediated 5 ' processing . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , we found that 12 o tetradecanoylphorbol 13 acetate ( TPA ) induced cyclooxygenase 2 ( COX 2 ) , but not COX 1 , protein expression in HL 60 cells , and the addition of arachidonic acid ( AA ) in the presence or absence of TPA significantly reduced the viability of HL 60 cells , an effect that was blocked by adding the COX inhibitors , NS 398 and aspirin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These studies indicate that , in contrast to normotensive gastric mucosa , inhibition of COX 1 alone is sufficient to cause PHT gastric damage as a result of excessive NO that prevents the induction of NF kappaB and the compensatory increase in COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In humans and in the widely accepted model of piglets , both the COX 1 and the COX 2 isoforms are expressed in cerebral arteries . ^^^ Therefore we tested if specific inhibitors of COX 1 and / or COX 2 would differentially affect pial arteriolar responses to COX dependent stimuli in piglets . ^^^ Arteriolar responses were repeatedly tested 15 min after 4 administration of selective COX 1 and COX 2 inhibitors SC 560 and NS 398 ( 1 1 mg / kg ) , and nonselective inhibitors indomethacin ( 0 . 3 1 mg / kg ) , acetaminophen ( 30 mg / kg ) , and ibuprofen ( 30 mg / kg ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenase isoforms ( COX 1 , COX 2 ) may exert differential regulatory actions on enteric motor functions under normal or pathological conditions . ^^^ AIMS : To examine the occurrence and functions of COX 1 and COX 2 in the neuromuscular compartment of normal distal colon using human and murine tissue . ^^^ RESULTS : Reverse transcription polymerase chain reaction ( RT PCR ) showed mRNA expression of COX 1 and COX 2 in human and wild type mouse colonic muscle whereas only COX 2 or COX 1 was detected in COX 1 or COX 2 knockout animals . ^^^ Immunohistochemistry localised both isoforms in neurones of myenteric ganglia , COX 1 in circular layer myocytes , and COX 2 in longitudinal muscle . ^^^ Indomethacin ( COX 1 / COX 2 inhibitor ) , SC 560 ( COX 1 inhibitor ) , or DFU ( COX 2 inhibitor ) enhanced atropine sensitive electrically induced contractions of human longitudinal muscle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : The expression of COX 2 protein and mRNA was rapidly induced by the addition of IL 17 and LPS , whereas COX 1 expression was not affected by these factors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To examine the role of prostaglandin in this response , we investigated whether 24 h BUO changed the expression of cyclooxygenases ( COX 1 and 2 ) in the kidney and tested the effect of the selective COX 2 inhibitor parecoxib ( 5 mg . kg ( 1 ) . day ( 1 ) via osmotic minipumps ) on AQPs and sodium transport . ^^^ BUO caused a significant 14 fold induction of inner medullary COX 2 ( 14 . 40 + / 1 . 8 vs . 1 . 0 + / 0 . 4 , n = 6 ; P < 0 . 0001 ) and a reduction in medullary tissue osmolality , whereas COX 1 did not change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Matrine had inhibitory effect on the mRNA and protein expression of COX 2 , and synthesis of PGE 2 in colon cancer HT 29 cell line , but had no effect on COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Compounds selectively blocking COX 2 received special attention due to their minimal impact on COX 1 that provides good anti inflammatory and analgesic effect with simultaneous dramatic reduction of ulcerogenic activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Synthesis and biological evaluation of a new class of acyl derivatives of 3 amino 1 phenyl 4 , 5 dihydro 1H pyrazol 5 one as potential dual cyclooxygenase ( COX 1 and COX 2 ) and human lipoxygenase ( 5 LOX ) inhibitors . ^^^ A series of acyl derivatives of 3 amino 1 phenyl 4 , 5 dihydro 1H pyrazol 5 one as potential human 5 LOX and COX 1 and COX 2 inhibitors structurally related to the 1 phenyl 3 pyrazolidinone ( phenidone , 1 ) have been synthesized and the activity against COX 1 , COX 2 and human 5 LOX enzymes has been evaluated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The initial step in the formation of prostanoids , i . e . , the conversion of free arachidonic acid ( AA ) to prostaglandin ( PG ) G ( 2 ) and then to PGH ( 2 ) , is controlled by two PGH synthases ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Fifteen minutes before surgery , rats received intrathecally the COX 1 preferring inhibitor , ketorolac , the specific COX 1 inhibitor , SC 560 , the COX 2 inhibitor , NS 398 , or vehicle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , MNNG decreased the levels of COX 2 mRNA and protein expression without significant changes in the levels of COX 1 , which was correlated with inactivation of the reporter construct of a COX 2 promoter and decrease in prostaglandin E 2 synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Small portions of 54 SLNs from 37 patients undergoing selective lymphadenectomy were subjected to quantitative reverse transcriptase polymerase chain reaction ( qRT PCR ) to quantify messenger RNA ( mRNA ) transcripts of the following genes : tyrosinase , telomerase , cyclooxygenase 1 ( COX 1 ) , COX 2 , granulocyte macrophage colony stimulating factor ( GM CSF ) , interleukin 2 ( IL 2 ) , interferon gamma ( IFN gamma ) , IL 4 , IL 10 and IL 12 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IHC was performed for estrogen ( ER ) and progesterone ( PR ) receptor , COX 2 , COX 1 , and aromatase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : BDL , Sham and Control Hartley guinea pig gallbladders were placed in cell culture , grown to confluence and underwent Western Blot analysis for smooth muscle cell content of COX 1 , COX 2 , Prostacylin Synthase , actin , caldesmon , vinculin , meta vinculin and tropomyosin and were assayed for basal release of 6 keto PGF ( 1alpha ) , PGE 2 and TxB 2 by EIA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS AND MATERIALS : To begin to determine the contributions of other enzymes involved in PGE 2 production , we examined protein levels of COX 1 and COX 2 as well as 2 PGE synthases ( membrane and cytosolic PGES ) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AZD 3582 [ 4 ( nitrooxy ) butyl ( 2S ) 2 ( 6 methoxy 2 naphthyl ) propanoate ] is a COX inhibiting nitric oxide donor that inhibits COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The nonselective cyclooxygenase ( COX ) inhibitors indomethacin or pyroxicam , or the selective COX 2 inhibitors DFU , NS 398 or rofecoxib , but not the selective COX 1 inhibitor SC 560 , all abolished BK induced relaxation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This research has culminated in the development of selective cyclooxygenase 2 ( COX 2 ) inhibitors that act on the inducible , inflammatory COX enzyme , but do not affect the constitutive prostaglandin synthesis in cells that is mediated via COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Those wounds were characterized by a reduced expression of COX 1 and the presence of strongly elevated levels of COX 2 when compared with conditions observed in healthy animals . ^^^ Resolution of the diabetic and impaired wound healing phenotype by systemic administration of leptin into ob / ob mice increased COX 1 expression in wound margin keratinocytes and decreased COX 2 expression in inner wound areas to levels found in wild type animals . ^^^ Accordingly , only late wound tissue from SC 560 treated ( selective COX 1 inhibitor ) but not celecoxib treated ( selective COX 2 inhibitor ) ob / ob mice exhibited a severe loss in PGE 2 , PGD 2 , and prostacyclin at the wound site , and this change was associated with reduced keratinocyte numbers in the neo epithelia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A small set of substituted 1 , 5 diarylpyrrole 3 acetic and glyoxylic acid derivatives have been synthesized , and their cyclooxygenase ( COX 1 and COX 2 ) inhibiting properties have been evaluated . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
DNA sequence of European corn borer , Ostrinia nubilalis ( Hubner ) ( Lepidoptera : Crambidae ) , mitochondrial cytochrome c oxidase 1 ( cox 1 ) and 2 ( cox 2 ) genes were characterized and used for population genetic analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Vasoactive prostanoids are generated from arachidonic acid by COX 1 and COX 2 in the mouse . ^^^ Pulmonary pressor and systemic depressor responses were attenuated by SC 560 and nimesulide , inhibitors of COX 1 and COX 2 , in doses that did not alter responses to injected prostanoids . ^^^ Pulmonary and systemic pressor responses to angiotensin 2 injections and systemic pressor responses to angiotensin 2 infusion were not modified by COX 1 or COX 2 inhibitors but were attenuated by losartan . ^^^ Systemic depressor responses to arachidonic acid were smaller in COX 1 and COX 2 knockout mice , whereas responses to angiotensin 2 , norepinephrine , U 46619 , endothelin 1 , and PGE ( 1 ) were not different in COX 1 and COX 2 knockout and wild type control mice . ^^^ These results suggest that vasoactive prostanoids with pulmonary pressor and systemic vasodepressor activity are formed by COX 1 and COX 2 and are consistent with Western blot analysis and immunostaining showing the presence of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunostaining was performed for COX 1 , COX 2 , hPGDS , mPGES , TXS , CD 34 , vascular endothelial growth factor ( VEGF ) , and basic fibroblastic growth factor ( bFGF ) . ^^^ The mean immunostaining scores for COX 1 , COX 2 , mPGES , and TXS were significantly higher for cases with more metastatic organs who had NSCLC . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 is constitutively expressed in cells , COX 2 is inducible and is upregulated in response to many signals . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 , are involved in production of prostanoids in the kidney . ^^^ In contrast to COX 2 , COX 1 expression was 30 % lower in ZDF 12 . ^^^ CONCLUSION : Renal cortical COX 2 protein expression and function were increased in ZDF rats , as compared to controls , whereas COX 1 exhibited opposite regulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indeed , treatment with rofecoxib diminished the lost of COX 1 caused by DSS in the crypt epithelium whereas expression of COX 2 remained unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSION : Our results demonstrate that there is positive feedback regulation of COX 2 expression by PG metabolites , but not COX 1 , indicating that PG levels per se do not play an important role in the compensatory regulation between the two COX isoenzymes , but may play an important role in mediating increased COX 2 expression and activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Further , P2X4R+ cells coexpressed the intracellular regulators of signalling cascades , COX 1 ( > 20 % ) , COX 2 ( > 5 % ) , RhoA ( > 60 % ) and RhoB ( > 10 % ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases ( COX 1 and COX 2 ) catalyze the conversion of arachidonic acid to prostaglandins . ^^^ Whereas overwhelming evidence suggests a role for COX 2 in a variety of cancers , the contribution of COX 1 remains much less explored . ^^^ We have previously shown that human epithelial ovarian tumors have increased levels of COX 1 but not COX 2 . ^^^ Using multiple approaches , we observed that OSE cells and the tumors comprised of these cells express high levels of COX 1 but not COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is referred to as a constitutive enzyme involved in haemostasis , whereas COX 2 is an inducible enzyme expressed in inflammatory diseases and cancer . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins and other eicosanoids derived from COX 1 and COX 2 are involved in a variety of physiologic and pathologic processes in the gastrointestinal tract . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Discovery of a second cyclooxygenase , COX 2 , led to the hypothesis that NSAID side effects could be decreased , as the inhibition of COX 2 is more directly implicated in ameliorating inflammation while the inhibition of COX 1 is related to adverse effects in the GI tract . ^^^ This article provides an overview on the therapeutic use of selective COX 2 inhibitors for relief of acute pain , largely based on clinical trials in patients undergoing the surgical removal of impacted third molars , with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX 1 / COX 2 inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 ) responsible for the synthesis of arachidonic acid metabolites . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Anti inflammatory effects of NSAIDs are mediated by COX 2 inhibition , while COX 1 inhibition is responsible for gastric prostaglandin inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expressions of COX 2 and COX 1 were assessed by Western blotting , and the myocardial prostaglandin ( PG ) E 2 and 6 keto PGF ( 1 alpha ) contents were measured using enzyme immunoassays . ^^^ After 24 h , the anti infarct effect was associated with enhanced myocardial levels of COX 2 , PGE 2 , and 6 keto PGF ( 1 alpha ) , and no changes in COX 1 protein levels were found . ^^^ Cardioprotection and increases in PGE 2 and 6 keto PGF ( 1 alpha ) were completely abolished by the COX 2 selective inhibitor NS 398 and the non selective COX inhibitor indomethacin , whereas the COX 1 selective inhibitor SC 560 had no effect . ^^^ After 48 h , up regulation of myocardial PGE 2 and 6 keto PGF ( 1 alpha ) was also observed , and COX 1 expression was enhanced markedly , but only a slight increase in COX 2 expression was apparent . ^^^ CONCLUSIONS : Morphine confers delayed cardioprotection via a COX dependent pathway ; COX 2 is essential for the cardioprotection observed in the initial stage ( 24 h ) , whereas , in the final stage ( 48 h ) , cardioprotection is mediated by COX 1 in concert with COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The main mechanism of action of non steroidal anti inflammatory drugs ( NSAIDs ) is the inhibition of cycloxygenases COX 1 and COX 2 . ^^^ In contrast , no effects were found after treatment of EC with the unselective COX 1 / COX 2 inhibitor indomethacin ( 30 microM ) , the potent and selective 5 LOX inhibitor , ZD 2138 ( 30 microM ) , the mainly COX 2 inhibitor aceclofenac ( 30 microM ) , the selective COX 2 inhibitor celecoxib ( 30 microM ) and the combination of ZD 2138 with the selective COX 2 inhibitor celecoxib ( 30 microM ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROCEDURE : COX 1 and COX 2 activities in heparinized whole blood samples were induced with calcium ionophore and lipopolysaccharide , respectively . ^^^ The COX 1 and COX 2 assays were standardized , such that time courses of incubation with the test compounds and conditions of COX expression were as similar as possible in the 2 assays . ^^^ Inhibition of thromboxane B 2 production , measured by use of a radioimmunoassay , was taken as a marker of COX 1 and COX 2 activities . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Overexpression of the COX 2 translational activator , Pet111p , prevents translation of COX 1 mRNA and cytochrome c oxidase assembly in mitochondria of Saccharomyces cerevisiae . ^^^ Respiratory growth is partially restored by a chimeric COX 1 mRNA bearing the untranslated regions of the COX 2 mRNA , and by overproduction of the COX 1 mRNA specific activators , Pet309p and Mss51p . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Resident peritoneal macrophages , which express COX 1 , were pretreated with lipopolysaccharide to induce COX 2 . ^^^ The selective COX 2 inhibitor , SC 236 , reduced PG G and PG production by 49 and 17 % , respectively , indicating a significant role for COX 1 in PG G and especially PG synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Fifty two surgical specimens were immunohistochemically labeled for Cox 1 and Cox 2 . ^^^ RESULTS : In chronically inflamed tissue the expression of Cox 1 and Cox 2 was strongly labeled . ^^^ However , in nasal polyps the staining pattern of Cox 1 was similar , but Cox 2 expression in epithelial cells was significantly less than in inflamed , nonpolypous specimens . ^^^ CONCLUSION : These data suggest that while Cox 1 is strongly up regulated , Cox 2 expression is significantly lower in epithelial cells of nasal polyps than in those of chronic sinusitis without polyps . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases , COX 1 and COX 2 , are crucial in the metabolic pathway leading to the generation of prostanoids . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Differential expression of COX 1 and COX 2 in the gastrointestinal tract of the rat . ^^^ The aim of this study was to use immunohistochemistry with morphometry to investigate COX 1 and COX 2 expression in the normal rat gastrointestinal ( GI ) tract and examine if sites of ulceration previously observed with long term COX 2 inhibitor administration in mice correlate with differential COX 1 / COX 2 expression . ^^^ In contrast , COX 1 positive cells within the lamina propria were evenly distributed along the GI tract but were present in higher numbers than COX 2 positive cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although N acetyl 3 carboxymethyl 6 fluorobenzenesulfonamide [ 14 , COX 1 IC 50 = 2 . 26 microM ; COX 2 IC 50 = 0 . 012 microM ; COX 2 selectivity index ( SI ) = 188 ] and N acetyl 3 carboxymethyl 6 ( 4 isopropoxyphenyl ) benzenesulfonamide ( 20c , COX 1 IC 50 > 100 microM ; COX 2 IC 50 = 0 . 15 microM ; COX 2 SI > 667 ) exhibited potent in vitro COX 2 inhibitory activity and high COX 2 selectivity , both compounds were inactive anti inflammatory agents in a carrageenan induced rat paw edema assay . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase 2 ( COX 2 ) selective inhibitor core structure , 3 [ 4 ( methylsulfonyl ) phenyl ] 5 ( trifluoromethyl ) ( 2 pyridyl ) phenyl ketone ( 20 ) , with COX 2 IC 50 = 0 . 25 microM and COX 1 IC 50 = 14 microM ( human whole blood assay ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin endoperoxide synthases ( PTGS ) , commonly referred to as cyclooxygenases ( COX 1 and COX 2 ) , catalyze the key step in the synthesis of biologically active prostaglandins ( PGs ) , the conversion of arachidonic acid ( AA ) into prostaglandin H 2 ( PGH 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Oral application of everolimus ( 3 mg kg ( 1 ) day ( 1 ) ) to male Sprague Dawley rats ( 175 200 g ; n=8 ) for 7 days lowered COX 2 expression in the rat renal cortex and outer medulla , while COX 2 expression in the inner medulla as well as COX 1 expression remained unaltered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition in horse blood by phenylbutazone , flunixin , carprofen and meloxicam : an in vitro analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to compare the in vivo effects on free radical metabolism of 2 non steroidal anti inflammatory drugs ( NSAIDs ) : tenoxicam , an oxicam preferentially cyclooxygenase 1 ( COX 1 ) inhibitor , and celecoxib , a sulfonamide selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , in a COX 1 whole blood assay ( WBA ) PM extract was not effective while in a COX 2 WBA , PM extract decreased PGE 2 production indicating COX 2 specific inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The two cyclooxygenase isoenzymes COX 1 and COX 2 were chosen as targets and the corresponding pharmacophore models were generated by our research . ^^^ The COX 1 and COX 2 inhibiting activities of these compounds were established in an enzyme assay and compared with the predicted hits obtained from the VS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Experiments with selective inhibitors of COX 1 ( SC 560 ) and COX 2 ( NS 398 and Cayman 10404 ) , indicated that COX 2 , but not COX 1 , was involved in 6 OHDA toxicity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Etodolac also appears to be COX 1 sparing but may have variable effects on COX 2 depending on the tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here , we demonstrate that besides COX 2 , which is the prominent COX isoform in the brain and particularly in the hippocampus , the constitutive isoform , COX 1 also contributes to prostaglandin ( PG ) synthesis and oxidative damage following in vivo acute activation of hippocampal NMDA glutamate receptors . ^^^ The relative contribution of the two isoforms is dynamically regulated , as the COX 2 selective inhibitor NS 398 immediately prevented PGE 2 and 15 F ( 2t ) IsoP formation during the application of NMDA , whereas the COX 1 selective inhibitor SC 560 was effective only 1 h after agonist infusion . ^^^ Our data suggest that , although COX 2 is the prominent isoform , COX 1 activity may significantly contribute to excitotoxicity , particularly when considering the amount of lipid peroxidation associated with its catalytic cycle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although none of these ester prodrugs ( 11 16 ) exhibited in vitro cyclooxygenase ( COX ) inhibitory activity against the COX 1 and COX 2 isozymes ( IC ( 50 ) > 100 microM ) , all of the compounds ( 11 16 ) significantly decreased carrageenan induced rat paw edema . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The inhibitor of cyclooxygenase 1 ( COX 1 ) , SC 560 , did not affect the basal tone of arterioles , whereas NS 398 , an inhibitor of COX 2 , caused a significant shift in the arteriolar pressure diameter curve of vessels from db / db mice ( at 80 mm Hg , 76+ / 3 % ) but not in those of control mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Human PDL cells obtained from periodontally healthy subjects were stimulated with vehicle or IL 1alpha in the presence or absence of indomethacin ( a COX 1 / COX 2 inhibitor ) , NS 398 ( a specific COX 2 inhibitor ) , PGE 2 , EP receptor agonists , dibutyryl cAMP , and forskolin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the PGE 2 production by enzyme linked immunosorbent assay , and cyclooxygenase ( COX 1 and COX 2 ) mRNA expression by RT PCR in cultured cells treated with or without CsA . ^^^ TAL cells produce PGE 2 mainly by COX 1 in steady state and by COX 2 in stimulated state by lipopolysaccharide ( LPS ) . ^^^ The mRNA expression of COX 1 is not affected and COX 2 is decreased in CsA treated TAL cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
INDO PA , which is highly selective for COX 2 in vitro , reduced platelet thromboxane production by 61 % in vivo , indicating partial inhibition of COX 1 in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Raloxifene , at 0 . 1 10 nM , increased the mRNA expression of COX 1 and the protein content of both COX 1 as well as COX 2 . ^^^ Although treatment with either the selective COX 1 inhibitor SC 560 or the selective COX 2 inhibitor NS 398 significantly diminished prostacyclin release ( 20 % + / 5 % and 24 % + / 7 % , respectively ) , co treatment with raloxifene and either SC 560 or NS 398 was followed by a smaller increase than that achieved by raloxifene alone . ^^^ CONCLUSION ( S ) : Raloxifene increased HUVEC prostacyclin release through a mechanism possibly distinct from the classical ER pathway and involving enhanced COX 1 and COX 2 expression and activity . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
For this purpose , acetylcholine ( ACh ) relaxations in aortic segments from both strains were analyzed in absence and presence of the cyclooxygenase 1 ( COX 1 ) and COX 2 inhibitor indomethacin , the specific COX 2 inhibitor NS 398 , the TP receptor antagonist ( SQ 29 548 ) , the thromboxane A 2 ( TXA 2 ) synthase inhibitor furegrelate , and the prostacyclin ( PGI 2 ) synthesis inhibitor tranylcypromine ( TCP ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Skin reactions triggered by aspirin are associated with the inhibition of cyclooxygenase , specifically COX 1 , but not COX 2 , and are characterized by overproduction of cysteinyl leukotrienes ( cys LTs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We conclude that the gastric ulcerogenic properties of NSAIDs are not accounted for solely by the inhibition of COX 1 and require the inhibition of both COX 1 and COX 2 , the inhibition of COX 1 up regulates COX 2 expression in association with gastric hypermotility , and PGs produced by COX 2 counteract the deleterious influences of the COX 1 inhibition . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Preclinical and clinical studies suggest that CINOD inhibit COX 1 and COX 2 activities while cause less adverse effects on gastrointestinal tract in comparison to conventional NSAIDs and coxibs and reduce systemic blood pressure . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Coexpression of cyclooxygenases ( COX 1 , COX 2 ) and vascular endothelial growth factors ( VEGF A , VEGF C ) in esophageal adenocarcinoma . ^^^ Our study was initiated to test whether expression of COX isoforms ( COX 1 and COX 2 ) is linked to expression of potent inducers of angiogenesis [ vascular endothelial growth factor ( VEGF ) A ] and lymphangiogenesis ( VEGF C ) in esophageal adenocarcinoma . ^^^ One hundred twenty three esophageal adenocarcinomas were investigated by means of quantitative reverse transcription PCR for expression of COX 1 , COX 2 , VEGF A , and VEGF C . ^^^ RNA expression levels of COX 1 and COX 2 varied markedly in carcinoma tissues and correlated significantly with each other ( P < 0 . 001 , r = 0 . 726 ) . ^^^ Furthermore , COX expression correlated with expression of VEGF A ( COX 1 : P < 0 . 001 , r = 0 . 753 ; COX 2 : P < 0 . 001 , r = 0 . 764 ) and VEGF C ( COX 1 : P < 0 . 001 , r = 0 . 778 ; COX 2 : P < 0 . 001 ; r = 0 . 613 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , BMK reduced prostaglandin E 2 ( PGE 2 ) production in mouse peritoneal macrophages stimulated with lipopolysaccharide , whereas no influence on the activity of inducible NO synthase ( iNOS ) , cyclooxygenase 2 ( COX 2 ) or cyclooxygenase 1 ( COX 1 ) was observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A nonselective COX inhibitor ( indometacin ) and a selective COX 1 inhibitor ( SC 560 ) strongly inhibited PGE 2 production by the three cell lines , while selective COX 2 inhibitors ( NS 398 and rofecoxib ) did not inhibit PGE 2 production . ^^^ In addition , increased expression of COX 1 , not COX 2 protein was observed in the mass of ovarian cancer tissues from 22 patients when compared with that in normal tissue . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects of NSAIDs ( ibuprofen , piroxicam , and indomethacin ) , a COX 1 selective inhibitor ( SC 560 ) , and COX 2 selective inhibitors ( celecoxib , niflumic acid , nimesulide , NS 398 , and SC 58125 ) on aromatase activity and CYP 19 expression were investigated in breast cancer cell culture systems . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A serious side effect of COX 1 and COX 2 inhibitors is renal damage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Although COX 2 , in contrast to the cyclooxygenase 1 ( COX 1 ) isoform , is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation , experimental and clinical studies have shown that COX 2 is constitutively expressed in tissues like the kidney or vascular endothelium , where it executes important physiological functions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We also studied the effects of thalidomide on COX 1 , COX 2 or bcl 2 expression , TNFalpha , VEGF , GSH and cytochrome c in these cells . ^^^ Thalidomide reduced COX 2 expression accompanied by a decrease of bcl 2 protein , TNFalpha , VEGF , GSH and an increased cytochrome c , but had no effect on that of COX 1 , in MCF 7 and HL 60 . ^^^ Effect of thalidomide on COX 1 and COX 2 in vivo was consistent with that of in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Real time PCR studies showed that mRNA levels of PGIS , COX 1 , and COX 2 were similar between lean and ZDF vessels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 specific inhibitors , which have an improved safety profile , as compared to traditional NSAIDs that inhibit both the COX 1 and COX 2 enzymes , seem to be well suited drug candidates for CRC prevention . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The role of COX 1 and COX 2 in Alzheimer ' s disease pathology and the therapeutic potentials of non steroidal anti inflammatory drugs . ^^^ In this review we will focus on the role , expression and regulation of COX 1 and COX 2 in neurodegeneration and AD pathogenesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Melatonin and its metabolites , N 1 acetyl N 2 formyl 5 methoxykynuramine ( AFMK ) and N 1 acetyl 5 methoxykynuramine ( AMK ) , prevented COX 2 activation induced by LPS , without affecting COX 1 protein levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This includes two iso enzymes , COX 1 and COX 2 , working in concert with the activation of apoptosis , activation of immune surveillance , inhibition of proliferation , and inhibition of carcinogen activation . 5 Fluorouracil ( 5 FU ) has demonstrated activity against colorectal cancer , leading to apoptosis of neoplastic cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is becoming more evident that inhibition of COX 2 results in the analgesic and anti inflammatory actions of non steroidal anti inflammatory drugs ( NSAIDs ) , and that inhibition of COX 1 results in the adverse side effects seen with these compounds . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective COX 2 inhibitors increase the risk of myocardial infarction and stroke that is attributed to their ability to inhibit prostacyclin ( PGI 2 ) , lipoxins , resolvins , and endothelial nitric oxide ( eNO ) but not platelet COX 1 derived thromboxane A 2 ( TXA 2 ) . ^^^ In contrast , aspirin blocks both COX 1 and COX 2 enzymes that , in turn , increases intracellular concentrations of dihomo gamma linolenic acid ( DGLA ) , arachidonic acid ( AA ) , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) and reduced formation of eicosanoids . ^^^ On the other hand , such an increase is much less with specific COX 2 inhibitors since they do not block the formation of eicosanoids through COX 1 pathway . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
It is believed that the inhibition of cyclo oxygenase type 1 ( COX 1 ) causes much of this toxicity , while inhibition of COX type 2 ( COX 2 ) , which is induced by inflammatory stimuli , may confer the anti inflammatory effect . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is expressed constitutively in most tissues whereas COX 2 is induced by a wide variety of stimuli and was initially identified as an immediate early growth response gene . ^^^ In addition , COX 2 expression is markedly increased in 85 90 % of human colorectal adenocarcinomas while COX 1 levels remain unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since the discovery that the enzyme cyclooxygenase ( COX ) exists as two isoforms , the largely constitutive COX 1 and the mainly inducible COX 2 , much interest has centred on the development of drugs capable of selectively inhibiting COX 2 . ^^^ Early studies that investigated specific COX 2 inhibitors ( with no effect on the COX 1 isoform over the whole range of concentrations achieved in clinical usage ) are encouraging , as they demonstrate that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs given at equivalent doses . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The positive controls used in the COX assays were aspirin , Celebrex and Vioxx at 180 , 1 . 67 and 1 . 67 ppm , respectively , and showed 74 and 69 % , 5 and 82 % and 0 and 85 % COX 1 and COX 2 inhibition , respectively . ^^^ Anthocyanins 1 and 2 and cyanidin ( 3 ) inhibited COX 1 enzyme 50 . 5 , 45 . 62 and 96 . 36 % , respectively , at 100 ppm , whereas COX 2 inhibition was the highest for 3 at 75 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , recent concerns over the toxicity of systemic selective COX 2 inhibition and the realisation that COX 1 may also contribute to carcinogenesis have cast some doubt on COX 2 inhibition as a safe and effective chemoprevention strategy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression in osteoid osteomas . ^^^ Since the cyclooxygenases are thought to be the source of these prostaglandins , and the central target of NSAIDs , we evaluated the expression of cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) in osteoid osteoma tissues from patients following surgery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this model TA was a preferential inhibitor of COX 2 ( COX 1 : COX 2 IC 50 ratio=12 : 1 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS AND CLINICAL RELEVANCE : Tepoxalin has in vivo inhibitory activity against COX 1 , COX 2 , and 5 LOX in dogs at the current approved recommended dosage . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 is the major isoform responsible for prostanoid synthesis in healthy tissues , little information is available on the contribution of constitutive COX 2 to the various prostanoid synthetic pathways under non inflammatory conditions . ^^^ To evaluate further the role of COX 2 in prostanoid biosynthesis , rats were acutely treated with the selective COX 1 inhibitor SC 560 [ 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ] or the selective COX 2 inhibitors MF tricyclic [ 3 ( 3 , 4 difluorophenyl ) 4 ( 4 ( methylsulphonyl ) phenyl ) 2 ( 5H ) furanone ] and DFU [ 5 , 5 dimethyl 3 ( 3 fluorophenyl ) 4 ( 4 methylsulphonyl ) phenyl 2 ( 5H ) furanone ] . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenases 1 and 2 ( COX 1 and COX 2 ) are important in renal physiology and in many abnormal states . ^^^ METHODS : COX 1 and COX 2 transcripts and proteins were analyzed by semi quantitative RT PCR and immunohistochemistry in samples from human renal allografts obtained from nephrectomy because of irreversible acute rejection . ^^^ RESULTS : In samples with acute rejection , we detected higher expression of COX 2 mRNA in comparison with COX 1 ( p < 0 . 001 ) being COX 2 expression not different from COX 1 in samples from renal allografts without acute rejection . ^^^ COX 1 and COX 2 localization was in accordance with data described in literature , however COX 2 protein was higher in interstitial cells in the group with rejection than in the group without rejection ( p = 0 . 04 ) . ^^^ In addition , in samples with acute rejection COX 2 immunoreactivity was more prominent in podocytes ( p < 0 . 001 ) , in proximal tubules ( p < 0 . 001 ) , in collecting duct cells ( p = 0 . 003 ) and in interstitial cells ( p < 0 . 001 ) when compared with COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , TSA decreased the levels of COX 2 mRNA and protein expression without significant changes in the levels of COX 1 , which was correlated with an inhibition in prostaglandin E 2 synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The affinity of an inhibitor for COX 1 and COX 2 determinates its relative selectivity . ^^^ However , the primitive hypothesis of a dualism between an isoform totally inducible ( COX 2 ) and the other isoform constitutive ( COX 1 ) was not completely true . ^^^ The altered balance between prostacyclin and thromboxane , due to selective inhibition of COX 2 without reducing COX 1 , could promote a prothrombotic state and explain the observed increased cardiovascular risk . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , Chan Su decreased the levels of COX 2 mRNA and protein expression without significant changes in the levels of COX 1 , which was correlated with an inhibition in prostaglandin E ( 2 ) synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here , nucleotide composition was compared across 49 species of Metazoa ( 34 arthropods , 2 annelids , 2 molluscs , and 11 deuterosomes ) , and analyzed for a mtDNA fragment including six protein coding genes , i . e . , atp 6 , atp 8 , cox 1 , cox 2 , cox 3 , and nad 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we investigated the influence of Ibuprofen , Nimesulid and Rofecoxib , cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibitors and Budesonide on the nasal polyps fibroblasts proliferation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To test the analgesic effects of nonsteroidal antiinflammatory drugs on bone cancer pain , the authors examined the effects of oral administration of a cyclooxygenase 1 ( COX 1 ) selective inhibitor ( SC 560 ) , a COX 2 selective inhibitor ( celecoxib ) , and a nonselective COX inhibitor ( indomethacin ) on bone cancer pain and compared these effects to the effect of orally administered acetaminophen and morphine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of HSP 27 , COX 1 , and COX 2 was investigated in Tg ( huHSP 27 ) mice and Wt mice by immunohistochemistry and western blot analysis . ^^^ COX 1 and COX 2 levels did not change . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
General COX ( COX 1 and 2 ) inhibition by traditional NSAIDs ( non steroidal anti inflammatory drugs ) , such as aspirin , although chemopreventive , has some side effects , as do some conventional COX 2 selective NSAIDs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective inhibitors of COX 1 , SC 560 [ 5 ( 4 chlorophenyl ) 1 ( 4 methoxypjenyl ) 3 ( trifluoromethyl ) 1H pyrazole ] , and COX 2 , NS 398 ( N [ 2 ( cyclohexyloxy ) 4 nitrophenyl ] methanesulfonamide ) , were used to investigate the relative contribution of each enzyme . ^^^ Phytoestrogens also increased COX 2 mRNA expression and protein content without affecting COX 1 levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In contrast , vitamin E dose dependently ( 10 60 micromol / L ) inhibited cyclooxygenase ( COX ) activity but did not affect the expression of either COX 1 or COX 2 , indicating that the effect of vitamin E on COX activity was post translational . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The cultures underwent Western Blot analysis for smooth muscle cell content of COX 1 , COX 2 , Prostacyclin Synthase ( PS ) , or were incubated with CCK at 10 ( 8 ) M or 10 ( 6 ) M with and without indomethacin for 1h and analyzed for release of 6 keto PGF1alpha , PGE 2 and TxB 2 by EIA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The combination also enhanced the peroxisome proliferator activated receptor ( PPAR ) gamma expression , decreased the expression of cPLA 2 , mPGES and vascular endothelial growth factor ( VEGF ) , but had no effect on the expression of COX 1 or COX 2 in tumor tissues . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We consider both COX 2 and COX 1 selective inhibitors taking the V523I mutant of COX 2 to be a relevant structural model for COX 1 as confirmed by a variety of experimental and theoretical evidences . ^^^ For all COX 2 selective inhibitors under consideration , we find that free energies of binding become less favorable as the receptor changes from COX 2 to COX 1 , due to the weakening and / or loss of hydrogen bond and hydrophobic interactions that stabilize the inhibitors in the COX 2 active site . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These fluorinated compounds showed lower inhibitory activity toward COX 1 than the corresponding non fluorinated compounds 2a e with retained inhibitory activity against COX 2 resulting in modification of the balance of COX 1 / COX 2 inhibitions , and they showed little anticancer activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Four hours after NSAIDs , the following parameters were assessed : histomorphometric evaluation of gastric mucosal damage ; gastric mucosal levels of myeloperoxidase ( MPO ) , malondialdehyde ( MDA ) , reduced glutathione as an index of non proteic sulfhydryl compounds ( GSH ) , and prostaglandin E 2 ( PGE 2 ) ; mucosal cyclooxygenase 1 and 2 ( COX 1 , COX 2 ) mRNA expression by reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Indomethacin enhanced mucosal COX 2 expression , while not affecting COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We studied these responses in 96 mice that were COX 1 or COX 2 deficient ( / ) or sufficient ( + / + ) . ^^^ Neither monophasic fever nor the first phase of polyphasic fever was attenuated in the COX 1 / mice , but both responses were absent in the COX 2 / mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Non selective NSAIDs such as ibuprofen and naproxen , which inhibit both COX 1 and COX 2 , have proven highly effective and safe in the short term management of acute pain . ^^^ Since the genetic code is a triplicate code ( 3 nucleotides to form one amino acid ) , the retention of the intron in both species results in a frame shift in the RNA message and the production of a truncated protein with a completely different amino acid sequence than COX 1 or COX 2 lacking acetaminophen sensitivity . ^^^ Advances made through a combination of basic molecular biological and pharmacological techniques , and well designed randomized controlled clinical trials have demonstrated that the apparent gastrointestinal advantage of selective COX 2 inhibitors appears to be outweighed by their potential for cardiovascular toxicity and that acetaminophen ' s analgesic and antipyretic effects do not involve the inhibition of the COX 1 splice variant protein , putative COX 3 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Overexpression of COX 2 and decreased expression of COX 1 have been suggested to be characteristics of colon cancer . ^^^ The exact physiological role of COX 3 , an intron retaining splice variant of COX 1 , is not known , but it is suspected to play a role in transcriptional regulation of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective COX inhibition showed PAR 2 induced PGE 2 synthesis to be COX 1 dependent in esophageal myofibroblasts and both COX 1 and COX 2 dependent in colonic cells , consistent with the distribution of COX 1 and COX 2 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL 1beta and COX 2 were positive in the Schwann cells and vascular endothelial cells , while COX 1 was detected in the vascular endothelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These compounds are converted from arachnoidic acid ( AA ) by two isoforms of the cyclooxygenase ( COX ) enzyme , namely COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase ( COX ) isozymes have been characterized , COX 1 and COX 2 , that differ in terms of regulatory mechanisms of expression , tissue distribution , substrate specificity , preferential coupling to upstream and downstream enzymes and susceptibility to inhibition by the extremely heterogeneous class of COX inhibitors . ^^^ While the role of platelet COX 1 in acute coronary syndromes and ischemic stroke is firmly established through approximately 20 years of thromboxane metabolite measurements and aspirin trials , the role of COX 2 expression and inhibition in atherothrombosis is substantially uncertain , because the enzyme was first characterized in 1991 and selective COX 2 inhibitors became commercially available only in 1998 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Immunohistochemistry revealed that COX 1 and COX 2 proteins are increased in spinal motor neurons . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PROCEDURE : Selectivity of firocoxib for inhibiting COX 2 was determined by comparing the potency for inhibiting COX 1 with that of COX 2 in feline blood . ^^^ RESULTS : Blood concentrations resulting in 50 % inhibition of COX 1 and COX 2 activity in vitro were 75 + / 2 microM and 0 . 13 + / 0 . 03 microM , respectively , and selectivity for inhibiting COX 2 relative to COX 1 was 58 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Intracisternal pretreatment with SC 560 , a selective COX 1 inhibitor , or NS 398 , a selective COX 2 inhibitor , abolished intra articular administration of IL 1beta induced hyperalgesic response . ^^^ Intracisternal pretreatment with NS 398 , a selective COX 2 inhibitor , abolished the intracisternal administration of IL 1beta induced hyperalgesic response , while pretreatment with SC 560 , a selective COX 1 inhibitor , did not change IL 1beta induced hyperalgesic responses . ^^^ These results indicate that central COX 2 plays important role in the central administration of IL 1beta induced hyperalgesia and that central COX 1 / 2 pathways mediate peripheral administration of IL 1beta induced hyperalgesia in the TMJ . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Similarly , COX 1 , COX 2 , MEK or p 38 MAP kinase inhibitors reduced the nociceptive effect produced by PMA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro COX 1 / COX 2 isozyme inhibition structure activity studies identified 1 ( 3 methylsulfonylphenyl ) 2 ( 4 methylphenyl ) acetylene ( 12d ) as a potent COX 2 inhibitor ( IC ( 50 ) = 0 . 32 microM ) with a high COX 2 selectivity index ( SI > 320 ) comparable to the reference compound rofecoxib ( COX 2 IC ( 50 ) = 0 . 50 microM ; COX 2 SI > 200 ) . ^^^ The structure activity data acquired indicate that the acetylene moiety constitutes a suitable scaffold ( template ) to design novel acyclic 1 , 2 diarylacetylenes with selective COX 2 , or dual COX 1 / COX 2 , inhibitory activities . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Crude water and ethanolic extracts of five herbal remedies reported in the literature for traditional treatment of benign prostatic hyperplasia ( BPH ) and / or prostatitis were investigated for their effect on hydroxyl scavenging activity , antibacterial activity and their ability to inhibit cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) catalysed prostaglandin biosynthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two isoforms of COX , which are nearly indistinguishable in structure and mechanism , however , COX 2 oxygenates neutral derivatives of AA that are poor substrates for COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is a rate limiting enzyme in prostaglandin synthesis from arachidonic acid and exists in two isoforms : COX 1 and COX 2 . ^^^ This study examined the protein expression of COX 1 , COX 2 , mPGES 1 , cPGES and mPGES 2 in preimplantation mouse embryos by immunohistochemistry . ^^^ We found that the COX 1 , COX 2 , mPGES 1 , cPGES and mPGES 2 protein signals were all at a high level at the blastocyst stage . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs block the activity of both COX isozymes , COX 1 and COX 2 , which mediate the enzymatic conversion of arachidonate to prostaglandin H 2 ( PGH 2 ) and other prostaglandin ( PG ) metabolites . ^^^ Although COX 1 and COX 2 exhibit similar biochemical activity in converting arachidonate to PGH 2 in vitro , the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX 1 and COX 2 , tissue distribution , and availability of the prostanoid synthases . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Under hypertonic but not under isotonic conditions , splice variant specific degradation of Cox 1ir mRNA using RNA interference resulted in increased production of fully spliced Cox 1 and Cox 2 mRNA ( P = 0 . 002 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The PAR ( 2 ) triggered PGE ( 2 ) formation was attenuated by inhibition of the following signal pathway enzymes : cyclooxygenases 1 and 2 ( COX 1 and COX 2 , respectively ) , cytosolic Ca ( 2+ ) dependent phospholipase A ( 2 ) ( cPLA ( 2 ) ) , the mitogen activated protein kinases ( MAPKs ) , mitogen activated protein kinase / extracellular signal regulated kinase kinase ( MEK ) extracellular signal regulated kinase ( ERK ) and p 38 MAPK , Src family tyrosine kinase , epidermal growth factor ( EGF ) receptor tyrosine kinase ( EGFRK ) , and protein kinase C ( PKC ) , but not by inhibition of matrix metalloproteinases . ^^^ SLIGRL NH ( 2 ) also evoked a relatively delayed ( 15 min ) and persistent ( 30 min ) phosphorylation of p 38 MAPK , blocked by inhibitors of Src and EGFRK but not by inhibitors of COX 1 or COX 2 . ^^^ We conclude that PAR ( 2 ) triggered PGE ( 2 ) formation in A 549 cells involves a coordinated up regulation of COX 2 and mPGES 1 involving cPLA ( 2 ) , increased cytosolic Ca ( 2+ ) , PKC , Src , MEK ERK , p 38 MAPK , Src mediated EGF receptor trans activation , and also metabolic products of both COX 1 and COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
SKI306X did inhibit the expression of cyclooxygenase 2 ( COX 2 ) enzyme without affecting COX 1 and COX 2 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tumor growth , with and without provision of a classical cyclo oxygenase inhibitor ( indomethacin ) , was related to tumor content of COX 1 / COX 2 protein as well as to EP 1 EP4 and prostacyclin receptor expression . ^^^ The extent of tumor growth inhibition by COX inhibitors is not simply related to drug specificity on COX 1 or COX 2 pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Dithymoquinone , thymohydroquinone , thymol and thymoquinone , compounds derived from N . sativa seeds , were investigated for their in vitro anti inflammatory activities using cyclooxygenase 1 ( COX 1 ) and 2 ( COX 2 ) assays . ^^^ Thymol was the most active against COX 1 with an IC ( 50 ) value of 0 . 2 microM while thymohydroquinone and thymoquinone exhibited the strongest inhibitory effect on COX 2 with IC ( 50 ) values of 0 . 1 and 0 . 3 microM , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Three subunits of this complex ( COX 1 , COX 2 and COX 3 ) are encoded by mitochondrial ( mit ) DNA . ^^^ High resolution immunogold electron microscopy has been used to study the subcellular localization of COX 1 and COX 2 in rat tissue sections , embedded in LR Gold resin , using monoclonal antibodies for these proteins . ^^^ In immunogold labeling studies , the COX 1 and COX 2 antibodies showed strong and specific mitochondrial labeling in the liver , kidney , heart and pancreas . ^^^ In contrast to these compartments , the COX 1 or COX 2 antibodies showed only minimal labeling ( five to tenfold lower ) of the cytoplasm , endoplasmic reticulum and the nucleus . ^^^ Strong labeling with the COX 1 or COX 2 antibodies was also observed in highly purified ZGs from bovine pancreas . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two isoforms of this enzyme exist in mammalian and avian species : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin , a key molecule that stimulates the complex array of ulcer healing mechanism , gets synthesized in the mucosal cells by cyclooxygenase ( COX ) enzymes : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Anthocyanins and were not studied earlier for their inhibition of lipid peroxidation , cyclooxygenase enzymes ( COX 1 and COX 2 ) , and tumor cell proliferation . ^^^ Similarly , they inhibited COX 1 enzymes by 39 % and 49 % and COX 2 enzyme by 54 % and 48 % , respectively , at 100 microg / mL . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Recent evidence suggests that lineage specific terminal prostanoid synthases , including prostaglandin ( PG ) E 2 , PGD 2 , PGF2alpha , PGI 2 , and thromboxane synthases , show distinct functional coupling with upstream COX isozymes , COX 1 and COX 2 . ^^^ In terms of their localization and COX preference , terminal prostanoid synthases are classified into three categories : ( 1 ) the perinuclear enzymes that prefer COX 2 , ( 2 ) the cytosolic enzyme that prefers COX 1 , and ( 3 ) the translocating enzyme that utilizes both COXs depending on the stimulus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Classical NSAIDs like indomethacin inhibit both the constitutive COX 1 and the inducible COX 2 enzymes . ^^^ We also compared the neuroprotective effects of indomethacin with the selective COX 1 , COX 2 and 5 LOX inhibitors , SC 560 , NS 398 and NDGA , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
G Gly induced a dose dependent increase in cell proliferation that was insensitive to inhibition of either COX 1 or COX 2 , but was abolished by inhibition of the p 38 MAP kinase , ERK and NF kappaB pathways . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tricin inhibited activity of purified COX 1 and COX 2 enzyme preparations with IC ( 50 ) values of approximately 1 micromol / L . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX 1 and whole blood COX 2 and on purified ovine COX ( oCOX ) 1 and oCOX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cox 1 and Cox 2 protein level , tyrosine phosphorylation , and mitogen activated protein kinase ( MAP kinase ) activation were determined by Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGC 1 , a key regulator of cardiac mitochondrial ATP production , induces mitochondrial DNA ( mtDNA ) encoded genes such as cytochrome c oxidase ( COX ) subunit 1 , 2 , and 3 ( COX 1 , COX 2 , and COX 3 ) , which regulates mitochondrial oxidative phosphorylation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results suggest that PGF synthesized through COX 1 and PGF synthase plays an important physiological role in the kidney and that the expression of COX 2 in kidney is a useful maker for tumorigenesis of the renal call carcinoma in vivo . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In response to the adverse effects that can accompany nonselective NSAID use , selective cyclo oxygenase ( COX ) 2 inhibitors were developed to target the COX 2 isoenzyme , thus providing anti inflammatory and analgesic benefits while theoretically sparing the gastroprotective activity of the COX 1 isoenzyme . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 conversely promote and suppress ischemia reperfusion gastric injury in mice . ^^^ We examined the roles of both COX 1 and COX 2 in neutrophil activation and free radical production in ischemia reperfusion ( IR ) injury in the gastric mucosa of mice . ^^^ SC 560 , a selective COX 1 inhibitor ; NS 398 , a selective COX 2 inhibitor ; or rebamipide , a mucoprotective agent , was administered to mice 60 min before ischemia . ^^^ RESULTS : COX 2 expression was induced in gastric mucosa 60 min after reperfusion , whereas COX 1 expression remained unaltered . ^^^ Localization of COX 1 and ICAM 1 in IR injured mucosa was observed mainly in endothelial cells , while COX 2 expression was detected in mesenchymal cells such as mononuclear cells , spindle like cells and endothelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
H & E and immunohistochemical antibody ( MMP 1 , MMP 9 , IL 1 , IL 6 , TNF alpha , COX 1 , and COX 2 ) stained specimens were examined by 2 blinded observers using a histologic scale ( grade 0 = no staining to grade 4 = intense staining ) . ^^^ Cyclooxygenase enzymes ( COX 1 and COX 2 ) were also increased in group 2 ( P < . 001 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The esophageal lesions were significantly aggravated by prior administration of indomethacin and SC 560 ( a selective COX 1 inhibitor ) but not rofecoxib ( a selective COX 2 inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 , membrane bound prostaglandin E synthase 1 ( mPGES 1 ) , and lipocalin type prostaglandin D synthase ( L PGDS ) mRNA and protein were determined by RT PCR and western blot , respectively . ^^^ Endotoxin treatment ( 1 mg / kg ; 24 h before ) enhanced the expression of COX 2 , mPGES 1 , and L PGDS mRNA and protein in spinal cord , while there was no significant effect on COX 1 mRNA and protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We studied the influence of meloxicam , a non steroidal antiinflammatory drug with preferential inhibitory effects on COX 2 compared to COX 1 , on canine osteosarcoma ( D 17 ) cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of genes coding cytokines ( IL 1alpha , IL 1beta , IL 6 , TNF alpha , TNF beta ) and proteins ( COX 1 , COX 2 , cathepsin K , collagen types 1 , 2 and 10 ; osteocalcin , osteopontin ) was evaluated in femoral epiphyses by RNase Protection Assay and / or immunohistochemically . ^^^ The epiphysis of the 21 day old fetuses , presented physiological expression of COX 1 and COX 2 , as well as cathepsin K , collagen types 1 , 2 and 10 ; osteopontin , osteocalcin and TNF alpha . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have evaluated the cellular and intracellular co localization of mPGES 1 and COX 2 , as well as cPGES and COX 1 in human trophoblast cells by dual immunofluorescent staining . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 are two cyclooxygenase enzymes responsible for prostanoid production . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Genetic and pharmacological inhibition of COX 2 , but not COX 1 , blocked arginase 1 induction in vitro and in vivo . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study examined the cellular localization and antihypertensive function of high salt induced COX 2 expression in the renal medulla , with a parallel assessment of the function of COX 1 . ^^^ COX 2 protein expression in response to high salt loading , assessed by immunostaining , was found predominantly in inner medullary interstitial cells , whereas COX 1 protein was abundant in collecting duct ( CD ) and inner medullary interstitial cells and was not affected by high salt . ^^^ We compared mRNA expressions of COX 1 and COX 2 in CD vs . non CD cells isolated from aquaporin 2 green fluorescent protein transgenic mice . ^^^ A low level of COX 2 mRNA , but a high level of COX 1 mRNA , as determined by real time RT PCR , was detected in CD compared with non CD segments . ^^^ During high salt intake , chronic infusions of the COX 2 blocker NS 398 and the COX 1 blocker SC 560 into the renal medulla of Sprague Dawley rats for 5 days induced approximately 30 and 15 mmHg increases in mean arterial pressure , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This has been attributed to their ability to inhibit endothelial COX 2 derived prostacyclin ( PGI 2 ) but not platelet COX 1 derived thromboxane A 2 ( TXA 2 ) . ^^^ On the other hand , aspirin blocks both COX 1 and COX 2 enzymes without decreasing PGI 2 but blocks TXA 2 synthesis that explains its beneficial action in the prevention of coronary heart disease ( CHD ) . ^^^ The inhibitory action of aspirin on COX 1 and COX 2 enzymes enhances the tissue concentrations of dihomo gamma linolenic acid ( DGLA ) , arachidonic acid , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DHA ) . ^^^ In contrast , increase in the concentrations of DGLA , AA , EPA , and DHA is much less with specific COX 2 inhibitors since they do not block the formation of eicosanoids through COX 1 pathway . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The roles of COX 1 , COX 2 , and the inducible microsomal PGES 1 have been studied in models of pain and inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of the study was to determine whether arachidonic acid ( AA ) , E 2 , and PTH increase prostaglandin E ( 2 ) ( PGE ( 2 ) ) synthesis in MG 63 and MC3T3 E 1 osteoblastic cells and the level of mediation by COX 1 and COX 2 . ^^^ Both COX 1 and COX 2 affected the regulation of PGE ( 2 ) synthesis in MG 63 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the dynamic changes of the expression and activity of the two forms of cyclooxygenase ( COX 1 and COX 2 ) in animal model of gastric ulcer and their role in the pathological process of gastric ulcer . ^^^ RT PCR and Western blotting were used to detect the expression of COX 1 mRNA and COX 2 mRNA and their protein levels . ^^^ RESULTS : After the ulcer induction , the expression of COX 2 mRNA and its protein were highly induced at the ulcer base in inflammation stage ( 6 hours to 3 days ) and kept at a high level during the healing stage ( 3 days to 15 days ) , while the expression of COX 1 remained relatively stable . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX inhibitory activity of Zyflamend was determined by a spectrophotometric based assay using purified ovine COX 1 and COX 2 enzymes . ^^^ Zyflamend dramatically decreased COX 1 and COX 2 enzymatic activity . ^^^ Zyflamend inhibited both COX 1 and COX 2 enzymatic activities , suppressed cell growth , and induced apoptosis in LNCaP cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To prevent this side effect , the pharmaceutical industry developed NSAIDs that selectively inhibit the cyclooxygenase 2 ( COX 2 ) isoenzyme , which is inducible and expressed at sites of inflammation , while sparing the COX 1 isoenzyme , which is associated with gastric protection . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mammary gland , like most tissues , produces measurable amounts of prostaglandin E 2 ( PGE 2 ) , a metabolite of arachidonic acid produced by sequential actions of two cyclooxygenases ( COX 1 and COX 2 ) and three terminal PGE synthases : microsomal prostaglandin E 2 synthase 1 ( mPGES 1 ) , mPGES 2 , and cytosolic prostaglandin E 2 synthase ( cPGES ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we examined the ethanol extracts and fractions of three Clematis species , Clematis pickeringii , Clematis glycinoides and Clematis microphylla , on cyclooxygenase 1 ( COX 1 ) , cyclooxygenase 2 ( COX 2 ) and 5 lipoxygenase ( 5 LOX ) . ^^^ The ethanol extracts of three Clematis species inhibited the activities of COX 1 , COX 2 and 5 LOX in the different extents . ^^^ The stem extract of Clematis pickeringii showed the highest inhibitory activities among the three species on COX 1 , COX 2 and 5 LOX with the IC ( 50 ) values of 73 . 5 , 101 . 2 and 29 . 3 microg / mL . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIMS : We examined the dynamics of COX 1 , COX 2 , mPGES 1 , mPGES 2 , cytosolic PGES ( cPGES ) , and PGE 2 synthetic activity in rat acid reflux oesophagitis and the effects of COX 2 inhibitors on the severity of oesophagitis . ^^^ RESULTS : Expression of COX 2 and mPGES 1 was markedly increased in oesophagitis while modest changes in COX 1 , cPGES , and mPGES 2 expression were observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mRNA expression patterns of EGF , HB EGF , Amphiregulin , EGF receptor , IGF 1 , CSF 1 , IL 1 alpha , IL 1 beta , IL 1 receptor type 1 , IL 1 receptor antagonist , LIF , COX 1 , COX 2 , Mucin 1 , calcitonin , and rat USAG 1 mouse homologue , all of which are involved in the process of conceptus implantation to the endometrium , were examined during the estrous cycle by means of real time quantitative PCR . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase ( COX 1 and COX 2 ) , while COX 2 selective inhibitors have shown some efficacy in reducing polyp formation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Two cyclooxygenase ( COX ) isozymes have been characterized , COX 1 and COX 2 , that differ in terms of regulatory mechanisms of expression , tissue distribution , substrate specificity and preferential coupling to upstream and downstream enzymes . ^^^ While the role of platelet COX 1 in acute ischemic diseases is firmly established , the role of COX 2 in atherothrombosis is still uncertain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While COX 1 is critical for renal and systemic PGE ( 2 ) production , renal prostacyclin synthesis is apparently COX 2 dependent . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase selectivity was expressed as a ratio of the concentration of an NSAID that inhibited 50 % of the activity ( IC 50 ) of COX 1 to the IC 50 of COX 2 . ^^^ A ratio of < 1 . 0 indicated selectivity for COX 1 , whereas a ratio of > 1 . 0 indicated COX 2 selectivity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Biopsy mucosal samples were taken for determination of expression of mRNA for COX 1 and COX 2 by reverse transcriptase polymerase chain reaction ( RT PCR ) and of the mucosal generation of prostaglandin E 2 ( PGE 2 ) by RIA . ^^^ COX 1 mRNA was detected by RT PCR in the intact and melatonin treated gastric mucosa , while COX 2 mRNA , which was undetectable in the intact gastric mucosa , appeared in WRS exposed mucosa , especially in the melatonin treated animals and this was accompanied by increased generation of PGE 2 in gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Extracts obtained from 10 trees used in South African traditional medicine were screened for antibacterial , anti inflammatory ( COX 1 and COX 2 ) and anti cholinesterase activities and investigated for potential mutagenic effects using the Ames test . ^^^ In the anti inflammatory assay , 70 % of the investigated plant extracts ( 0 . 25 mg ml ( 1 ) ) inhibited both COX 1 and COX 2 activity ( > 50 % and 70 % for water and organic solvent extracts , respectively ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In diseased kidneys , COX 1 immunoreactive protein and mRNA levels were higher and COX 2 levels were lower compared with normal kidneys . ^^^ In contrast , COX activities were higher in diseased compared with normal kidneys for both COX 1 [ 0 . 05 + / 0 . 02 vs . 0 . 45 + / 0 . 11 ng prostanoids 10 min ( 1 ) 10 mg protein ( 1 ) ( P < 0 . 001 ) ] and COX 2 [ 0 . 64 + / 0 . 10 vs . 2 . 32 + / 0 . 22 ng prostanoids 10 min ( 1 ) . mg protein ( 1 ) ( P < 0 . 001 ) ] . ^^^ As the relative difference in activity was greater for COX 1 , the ratio of COX 1 / COX 2 was higher in diseased compared with normal kidneys , although the predominant activity was still due to the COX 2 isoform in both genotypes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The severity of lesions was significantly increased by pretreatment with indomethacin ( a nonselective COX inhibitor ) and rofecoxib ( a selective COX 2 inhibitor ) but not 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 ( trifluoromethyl ) 1H pyrazole ( SC 560 ; a selective COX 1 inhibitor ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A real time quantitative PCR analysis and correlation of COX 1 and COX 2 enzymes in inflamed dental pulps following administration of three different NSAIDs . ^^^ Nonsteroidal anti inflammatory drugs ( NSAIDs ) commonly used for pain management are traditionally cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) inhibitors , and more recently selective COX 2 inhibitors . ^^^ This study was designed to identify and quantify COX 1 and COX 2 gene expression level in inflamed rat molar pulps after administration of three NSAIDs : Celebrex , Vioxx , and Advil . ^^^ Real Time Quantitative Reverse Transcriptase Polymerase Chain Reaction assay , a relatively new PCR technique , was used to quantify COX 1 and COX 2 mRNA . ^^^ Statistical analysis demonstrated no significant differences in COX 1 and COX 2 levels among the drug groups . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX exists in two distinct isoforms , COX 1 and COX 2 , the latter being primarily involved in inflammation and cell proliferation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Double immunofluorescence was performed using antibodies against mPGES 1 , COX 1 , COX 2 , and CD 163 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When comparing COX isoforms ( COX 1 and COX 2 ) , the authors found that overlapping and mutually exclusively properties coexist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE ( 2 ) led to an increase of COX 2 mRNA and protein expression , whereas the expression of COX 1 remained unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the course of our survey of natural compounds inhibiting prostaglandin E 2 release and / or lipopolysaccharide ( LPS ) induced transcriptional stimulation via NF kappaB , a central regulator of inflammatory genes , from natural resources , we found garcinone B , a xanthone from callus tissue culture of Hypericum patulum , as a compound with such pharmacological activities , that is a derivative of gamma mangostin which potently inhibits COX 1 and COX 2 activities to reduce PGE 2 release from C 6 rat glioma cells , and inhibits IKK activity to prevent NF kappaB dependent COX 2 gene transcription . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs inhibit the enzymatic activity of cyclooxygenase 1 ( COX 1 ) and inducible COX 2 , which catalyze the first committed step in the synthesis of prostaglandins . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To see whether production of prostaglandins ( PGs ) is involved in the inhibitory effect of pine needle extract on pacemaker currents , we tested the effects of naproxen , a non selective cyclooxygenase ( COX 1 and COX 2 ) inhibitor , and AH 6809 , a prostaglandin EP 1 and EP 2 receptor antagonist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Pro inflammatory cytokines ( TNFalpha , IL1beta , IL 6 ) , adhesion molecule ICAM 1 , cyclooxygenase isoenzymes ( COX 1 , COX 2 ) , and the nuclear factor kappaB ( NF kappaB ) complex were analysed on SM co cultured with a T cell line , as intracellular protein expression by immunocytochemistry ( ICC ) and western blot analysis , as extracellular protein expression by ELISA assay , and as mRNA expression by reverse transcriptase multiplex PCR ( RT MPCR ) after treatment with Lef M ( 1 , 10 , 30 micromol / l ) alone or in combination with MTX ( 50 ng / ml ) . ^^^ Concordant decreased expression was observed for ICAM 1 , COX 1 , COX 2 , and the NF kappaB complex after Lef M+MTX treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The isolated compound was further tested for anti inflammatory activity using the cyclooxygenase enzyme assays ( COX 1 and COX 2 ) and for potential mutagenic effects using the Ames test . ^^^ In the anti inflammatory assays , anolignan B showed activity against both COX 1 ( IC ( 50 ) = 1 . 5 mM ) and COX 2 ( IC ( 50 ) = 7 . 5 mM ) enzymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , studies from several groups have established that both COX 1 and COX 2 have important functions in the maintenance of gastrointestinal mucosal integrity . ^^^ Thus , in the normal rat stomach lesions only develop when both COX 1 and COX 2 are inhibited . ^^^ On the other hand , in specific pathophysiological situations the isolated inhibition of either COX 1 or COX 2 without simultaneous suppression of the other COX isoenzyme is ulcerogenic . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
This study was designed to determine the effect of pioglitazone on gastric mucosal lesions induced in rats by topical application of 100 % ethanol and by 3 . 5 h of water immersion and restraint stress ( WRS ) with or without pretreatment with indomethacin ( 5 mg / kg i . p . ) to inhibit cyclooxygenase 1 ( COX 1 ) and COX 2 enzyme activities and L NNA ( 20 mg / kg i . p . ) to suppress nitric oxide ( NO ) synthase . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , all pigments tested gave COX 1 and COX 2 inhibition and showed a dose dependent growth inhibition against breast , colon , stomach , central nervous system , and lung tumor cells , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study investigated the role of non selective ( ketorolac or indomethacin ) or specific inhibitors of COX 1 ( SC 560 ) and COX 2 ( NS 398 ) in these effects . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In general , COX 1 but not COX 2 is expressed in healthy tissues of adults . ^^^ Vice versa , the genetic ablation of COX 2 , as well as of COX 1 , results in a reduced tumour burden in murine skin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Most of the genes important in the mitochondrial function ( ND 1 , ND 2 , ND 3 , ND 4 , ND4L , ND 5 , ND 6 , ATP 6 , ATP 9 , COX 1 , COX 2 and COB ) and protein synthesis ( SsrRNA and LsrRNA ) were localized . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Contrasting effects of cyclooxygenase 1 ( COX 1 ) and COX 2 deficiency on the host response to influenza A viral infection . ^^^ The purpose of the present study was to examine the effect of deficiency of COX 1 or COX 2 on the host response to influenza . ^^^ We used an influenza A viral infection model in wild type ( WT ) , COX 1 / , and COX 2 / mice . ^^^ Infection induced less severe illness in COX 2 / mice in comparison to WT and COX 1 / mice as evidenced by body weight and body temperature changes . ^^^ COX 1 / mice had enhanced inflammation and earlier appearance of proinflammatory cytokines in the BAL fluid , whereas the inflammatory and cytokine responses were blunted in COX 2 / mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In in vitro assays , loxoprofen sodium appeared inactive against recombinant human COX 1 and COX 2 , whereas loxoprofen SRS inhibited both . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases ( COX 1 and COX 2 ) catalyze the conversion of arachidonic acid to prostaglandins ( PGs ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
AIM : To determine whether ischemic preconditioning ( IP ) affects the development of edematous cerulein induced pancreatitis and to assess the role of cyclooxygenase 1 ( COX 1 ) , COX 2 , and heat shock protein 70 ( HSP 70 ) in this process . ^^^ Activity of COX 1 or COX 2 was inhibited by resveratrol or rofecoxib , respectively ( 10 mg / kg ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The production of PGE ( 2 ) and the gene expression of COX 1 , COX 2 , and PGE ( 2 ) receptors , including Ep 1 , Ep 2 , Ep 3 , and Ep 4 , were determined using enzyme linked immunosorbent assay ( ELISA ) and real time reverse transcription polymerase chain reaction ( real time RT PCR ) , respectively . ^^^ The expression of COX 1 , Ep 1 , Ep 2 , and Ep 3 receptors decreased on day 14 of the culture , whereas the expression of COX 2 and Ep 4 receptors increased significantly with the addition of LPS . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Several statistically significant regression expressions were obtained for both COX 1 and COX 2 inhibition using sequential multiple linear regression analysis method . ^^^ Two of these models were selected and validated further , which revealed the importance of Kier molecular flexibility index for COX 2 inhibitory activity and the number of hydrogen bond donor atoms for COX 1 inhibitory activity . ^^^ Additionally , linear correlation of molecular flexibility with COX 1 and COX 2 inhibitory activities revealed that flexibility of molecules at COX 2 active site can improve the selectivity of COX 2 inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In rodents and humans , COX 3 encodes proteins with completely different amino acid sequences than COX 1 or COX 2 and without COX activity ; therefore , it is improbable that COX 3 in these species plays a role in prostaglandin mediated fever and pain . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The concentration dependent constriction induced by clonidine was analyzed in the absence and presence of the nitric oxide synthase ( NOS ) inhibitor , Nomega nitro L arginine ( L NAME ) , cyclooxygenase ( COX 1 and COX 2 ) inhibitors , indomethacin , the specific COX 2 inhibitor NS 398 , the thromboxane prostanoid receptor antagonist SQ 29 , 548 and the thromboxane A 2 ( TXA 2 ) synthase inhibitor , furegrelate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , sebocytes constitutively produced cyclooxygenase 2 ( COX 2 ) , but not COX 1 , in vivo and in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We examined the effect of TFG extract on : ( 1 ) the response of rabbit platelets to ADP induced aggregation , ( 2 ) the contraction of mouse vas deferens induced by alpha , beta Me ATP ( a P ( 2 ) receptor agonist ; this receptor mediates the rapid phase of ADP and ATP evoked influx of Ca ( 2+ ) through a non specific cation channel in platelets ) , ( 3 ) alpha , beta Me ATP induced hyperalgesia in tail flick test in male rats and ( 4 ) the specific inhibition of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Endothelium dependent contractions occur in the aorta of wild type and COX 2 / knockout but not COX 1 / knockout mice . ^^^ Such endothelium dependent contraction was absent in the aorta of COX 1 knockout mice and present in that of COX 2 knockout mice . ^^^ Similar results were obtained in aortas of female wild type , COX 2 and COX 1 knockout mice . ^^^ These contractions , as in the aorta of the spontaneously hypertensive rat , are caused by endogenous agonists ( s ) of TP receptors produced by cyclooxygenase 1 , because they are observed in the aortas of COX 2 knockout mice but not in aortas of COX 1 knockout mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandin G / H synthases ( PGHS ) , commonly referred to as cyclooxygenases ( COX 1 and COX 2 ) , catalyze a key step in the synthesis of biologically active prostaglandins ( PGs ) , the conversion of arachidonic acid ( AA ) into prostaglandin H ( 2 ) ( PGH ( 2 ) ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We measured systolic blood pressure , HO activity , HO 1 , HO 2 , COX 1 and COX 2 protein expression , heme content , and nitrotyrosine levels as indices of oxidative stress . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study we examined the effect of nimesulide ( a preferential COX 2 inhibitor ) , rofecoxib ( a highly selective COX 2 inhibitor ) or naproxen ( a non selective COX inhibitor displaying high affinity towards the COX 1 isoenzyme ) on alcohol induced withdrawal symptoms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two primary related COX isoforms , the constitutively expressed COX 1 and the inducible COX 2 . ^^^ Although the expression of COX 1 and COX 2 has been demonstrated in the amnion , chorion , and decidua , relatively little information exists with regard to their expression and physiological function in the placenta during gestation . ^^^ In this study , we have elucidated the spatial and temporal patterns of COX 1 and COX 2 expression in the labyrinthine and junctional zones of the developing rat placenta , in the human term placenta , and in the BeWo human trophoblast model using semiquantitative RT PCR , Western blot , and immunohistochemical analyses . ^^^ The mRNA and protein expression of COX 1 and COX 2 were demonstrated in the developing rat placenta with increasing expression observed toward parturition . ^^^ COX 2 exhibited greater expression than COX 1 after mid gestation and had a corresponding shift in spatial expression from the labyrinthine to the junctional zone at term . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We found that expression of mutant N141I PS 2 resulting in apoptotic cell death in H 4 neuronal cells coincided with > 4 fold induction in the expression of the inducible form of COX 2 , but not the constitutive COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The compound , 3 ethylthio 5 ( 4 fluorophenyl ) 4 ( 4 methylsulfonylphenyl ) 4H 1 , 2 , 4 triazole ( 10d ) , exhibited a high in vitro selectivity ( COX 1 IC50=20 . 5 nM ; COX 2 IC50=1 . 8 nM ; SI=11 . 39 ) relative to the reference drug celecoxib ( COX 1 IC50=3 . 7 nM ; COX 2 IC50=2 . 2 nM ; SI=1 . 68 ) and also showed good anti inflammatory activity compared to celecoxib in a carrageenan induced rat paw edema assay . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NSAIDs inhibit cyclooxygenase 1 ( COX 1 ) and / or cyclooxygenase 2 ( COX 2 ) activity and considerable evidence supports a role for prostaglandins in cancer development . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We determined the effects of cyclooxygenase 1 ( COX 1 ; SC 560 ) , COX 2 ( SC 58125 ) , and inducible nitric oxide synthase ( iNOS ; 1400W ) inhibitors on atorvastatin ( ATV ) induced myocardial protection and whether iNOS mediates the ATV induced increases in COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study was to investigate the roles of cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) and prostaglandin ( PG ) on gastric mucosal integrity of partially sleep deprived ( PSD ) rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Novel 1 , 2 disubstituted imidazoles were synthesized and tested for COX 1 and COX 2 inhibition . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Licochalcone A had no effect on COX 1 dependent PGE 2 production , whereas indometacin ( 100 nM ) , a dual inhibitor of COX 1 and COX 2 , was very effective . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Time course of COX 1 and COX 2 expression during ischemia reperfusion in rat skeletal muscle . ^^^ In conclusion , hindlimb I / R induced a large overexpression of COX 2 but not COX 1 protein between 6 and 10 h after injury . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We prepared 11C labeled 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 ( trifluoromethyl ) 1H pyrazole ( [ 11C ] 1 ) and 4 [ 5 ( 4 methoxyphenyl ) 3 trifluoromethyl 1H pyrazol 1 yl ] benzenesulfonamide ( [ 11C ] 2 ) for imaging COX 1 and COX 2 isoforms , respectively , by positron emission tomography . [ 11C ] 1 and [ 11C ] 2 were synthesized in high radiochemical yields by O [ 11C ] methylation with [ 11C ] methyl triflate in acetone containing an equivalent of NaOH as a base with respect to the phenolic precursors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : A differentiation dependent diminution of COX 1 and COX 2 mRNA and cognate proteins in 3T3 L 1 cells was observed . ^^^ Immunocytochemistry revealed that COX 1 and COX 2 became intracellularly more diffuse upon differentiation , whereas mPGES was redistributed to the nuclear compartment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , PS liposome induced PGE 2 production was significantly suppressed by indomethacin , a preferential COX 1 inhibitor , but not by NS 398 , a selective COX 2 inhibitor . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Lumiracoxib is selective for COX 2 compared with COX 1 in the human whole blood assay with a ratio of 515 : 1 in healthy subjects and in patients with osteoarthritis or rheumatoid arthritis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , the role of COX 1 ( with or without impairment of COX 2 ) and the interaction between COX and NOS isoforms during healing are less clear . ^^^ Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX 1 and COX 2 deficiency and inhibition mouse models . ^^^ In this study , female wild type COX 1 ( / ) and COX 2 ( / ) mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle , selective COX 1 ( SC 560 ) , COX 2 ( celecoxib , rofecoxib , and valdedoxib ) , and unselective COX ( piroxicam ) inhibitors . ^^^ More severe healing impairment was found in dual ( SC 560 + rofecoxib ) and unselective ( piroxicam ) COX inhibition and combined COX impairment ( in COX 1 ( / ) mice with COX 2 inhibition and COX 2 ( / ) mice with COX 1 inhibition ) . ^^^ In the ulcerated repair tissue , COX 2 mRNA in COX 1 ( / ) mice , COX 1 mRNA in COX 2 ( / ) mice , and , remarkably , NOS 2 and NOS 3 mRNA in COX impaired mice were more upregulated than in wild type mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Current therapies include NSAIDs ' that inhibit cyclooxygenases ( COX 1 , COX 2 ) but have no effect on the production of leukotrienes or platelet activating factor ( PAF ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As analyzed by reverse transcriptase polymerase chain reaction ( RT PCR ) , all the cell lines constitutively expressed COX 1 , while COX 2 levels markedly varied among different cell lines . ^^^ Intact cells of ARH 77 converted 14C labeled arachidonic acid to prostaglandin E 2 , F2alpha , and D 2 , and this activity was dose dependently inhibited by selective COX 2 inhibitors ( SC 58125 and NS 398 ) , a non selective COX inhibitor ( indomethacin ) , and relatively high concentrations of a selective COX 1 inhibitor ( SC 560 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The aim of this study was to examine the expression pattern and regulation of COX 1 , COX 2 , membrane associated PGES 1 ( mPGES 1 ) , mPGES 2 and cytosolic PGES ( cPGES ) in rat uterus during early pregnancy and pseudopregnancy , and under delayed implantation . ^^^ At implantation site on day 6 of pregnancy , COX 1 immunostaining was highly visible in the luminal epithelium , and COX 2 immunostaining was clearly observed in the subluminal stroma . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indeed , we have recently observed that the dual COX 1 / COX 2 inhibitor indomethacin induces apoptosis in human hepatocellular carcinoma ( HCC ) cell lines more effectively than the selective COX 2 inhibitors , possibly implicating COX 1 in HCC . ^^^ The combination of the COX 1 inhibitor with nimesulide and CAY 10404 , two selective COX 2 inhibitors , resulted in additive effects on cell growth inhibition . ^^^ Overall , our previous and present results suggest that both COX 1 and COX 2 inhibitors may have potential therapeutic implications in HCC patients . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Amtolmetin guacyl ( AMG ) , a NSAID that inhibits both COX 1 and COX 2 , has an anti inflammatory effect comparable to that of traditional NSAIDs , with a better GI safety profile . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The discovery of two isoforms of this enzyme , COX 1 and COX 2 , and that the latter is inducible by inflammatory cytokines supported the hypothesis that its inhibition would result in a potent antiinflammatory effect and led to the rapid development of selective COX 2 inhibitors , collectively called coxibs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Peritoneal macrophages isolated from LDLR ( / ) mice reconstituted with COX 1 ( / ) marrow had increased lipopolysaccharide induced levels of COX 2 mRNA and protein expression . ^^^ Fetal liver cell transplantation studies revealed a 30 % increase in atherosclerosis in COX 1 ( / ) > LDLR ( / ) mice compared with COX 1 ( + / + ) > LDLR ( / ) mice , whereas the extent of atherosclerosis was unchanged in COX 1 ( / ) / COX 2 ( / ) > LDLR ( / ) mice . ^^^ These data demonstrate that platelet TX production does not aggravate early atherosclerotic lesion formation and that upregulation of COX 2 expression in COX 1 ( / ) macrophages is proatherogenic . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 2 but not COX 1 was dose and time dependently increased in S . pneumoniae infected BEAS 2B cells as well as in lungs of mice with pneumococcal pneumonia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Effects of COX 1 and COX 2 inhibitors on the firing of rat midbrain dopaminergic neurons possible involvement of endogenous kynurenic acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To discriminate between these effects we developed potent AKR1C inhibitors based on N phenylanthranilic acids that do not inhibit COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
As COX 2 was detected in human and canine osteosarcomas , we have evaluated the effect of the preferential COX 2 inhibitor meloxicam on an established D 17 canine osteosarcoma cell line , which expressed , as well as COX 1 and COX 2 also COX 3 ( as demonstrated by Western blot ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The possible involvement of cyclooxygenase ( COX ) isoforms in the IL 1beta mediated spinal PGE ( 2 ) production on the background of peripheral formalin inflammation was further evaluated with the selective COX 1 and COX 2 inhibitors . ^^^ The COX 2 inhibitor SC 58236 ( 15 mg / kg ) reduced the IL 1beta mediated PGE ( 2 ) increase in CSF by 86 % while the COX 1 inhibitor SC 58560 ( 15 mg / kg ) had less effect ( 28 % ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 protein expression was upregulated by SP with a peak at 100 nM and at 20 h ; in the same experimental conditions COX 1 protein expression was unchanged . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we have used a modified whole blood assay to compare the potencies of aspirin , celecoxib , diclofenac , indomethacin , lumiracoxib , meloxicam , naproxen , rofecoxib , sodium salicylate , and SC 560 as inhibitors of COX 1 and COX 2 in the presence of differing concentrations of protein . ^^^ Clearly , our findings show that the selectivity of inhibitors for COX 1 and COX 2 , which are taken to be linked to their efficacy and side effects , may change in different extracellular fluid conditions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The concentration of PGE 2 , the gene expression of cyclooxygenases ( COX 1 and COX 2 ) and level of apoptosis ( measured by caspase 3 activity ) are assessed during organogenesis in the embryos of streptozotocin induced diabetic rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Tween 20 extracts effectively inhibited both COX 1 and COX 2 cyclooxygenase activity . ^^^ As a comparison , the glycogen extract also demonstrated a similar though weaker effect on COX 1 and COX 2 enzymes . ^^^ Although the anti cytokine activity of the Tween 20 extract was destroyed by Proteinase K treatment , the anti COX 1 and anti COX 2 activity of both the extracts were not sensitive to protease treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
DNA from a nuclear gene , beta actin , and two mitochondrial genes , cytochrome c oxidase 1 and 2 ( Cox 1 and Cox 2 ) , were quantified by real time PCR . mtDNA content was correlated with age , exposure history , and other variables using multivariate regression analyses . ^^^ A significant increase ( P < 0 . 001 ) in mtDNA content was noted in smokers ( 31 % and 29 % increase for Cox 1 and Cox 2 , respectively ) and former smokers ( 31 % and 34 % ) when compared with never smokers . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expressions of renal COX 1 , COX 2 , and iNOS mRNA were analyzed by RT PCR ; additionally , COX 2 protein was estimated by Western blot method . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , there are no data available about the expression of COX 1 and only preliminary reports about the expression of COX 2 in biopsies of patients undergoing acute renal allograft rejection . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Specifically , we aimed to quantify and compare ( 1 ) leukocyte densities in three regions of fetal membranes and decidua before and during spontaneous labor at term , and ( 2 ) mRNA expression of interleukin ( IL ) 1beta , IL 6 , IL 8 , cyclo oxygenase type 1 ( COX 1 ) , and COX 2 in three regions of fetal membranes and decidua before and during spontaneous labor at term . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
All genes are encoded on the same DNA strand and include seven subunits of the reduced nicotinamide adenine dinucleotide ubiquinone oxireductase ( nad 1 , nad 2 , nad 3 , nad 4 , nad4L , nad 5 , and nad 6 ) , three subunits of cytochrome oxidase ( cox 1 , cox 2 , and cox 3 ) , apocytochrome b ( cob ) , three subunits of ATP synthase ( atp 6 , atp 8 , and atp 9 ) , the small and large ribosomal RNAs ( rns and rnl ) , and 25 tRNAs . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostacyclins are powerful vasodilators and potent inhibitors of platelet aggregation which are produced from free arachidonic acid through the catalytic activity of two COX : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blotting showed that the expression of COX 2 was always higher in the HeLa / bcl 2 cells than in the HeLa / vector cells under the both of treated and untreated with H2O2 , while the level of COX 1 was relative stable in the both strains . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the early 1990s , it was discovered that enzymatic reactions producing prostaglandins were regulated by two cyclooxygenase enzymes , one producing prostaglandins constitutively in tissues like the stomach , prostaglandin endoperoxide H synthase 1 ( PGHS 1 or COX 1 ) , and another induced by mitogens or inflammatory mediators ( PGHS 2 or COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 inhibitors and antifungal agents from Croton hutchinsonianus . ^^^ Compounds 1 2 ( IC ( 50 ) 2 . 11 4 . 95 microg / ml ) exhibited potent but non selective activity against the enzymes cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) whereas 3 ( IC ( 50 ) 1 . 88 microg / ml ) preferentially inhibited the enzyme COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Activation of both COX 1 and COX 2 seems to be essential for this novel response to LPS , which also involves cPLA ( 2 ) , p 38 MAPK , NF kappaB , and an unidentified NF kappaB independent , labile regulatory protein . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here , we show that the serine protease thrombin , a PAR 1 selective peptide ( TFLLRN ) , and SLIGKV ( PAR 2 selective peptide ) induce cyclooxygenase 2 ( COX 2 ) protein and mRNA expression in human endothelial cells without modifying COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Second , to assess the mechanism of relapse , intestinal inflammation was quantitated ( fecal calprotectin ) before and during treatment ( 20 patients / group ) with acetaminophen , naproxen ( topical effect , COX 1 and 2 inhibitor ) , nabumetone ( COX 1 and 2 inhibitor ) , nimesulide ( selective COX 2 inhibitor ) , and low dose aspirin ( selective COX 1 inhibition ) . ^^^ Selective COX 2 inhibition with nimesulide and COX 1 inhibition with low dose aspirin appear to be well tolerated in the short term . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
However , other COX 2 preferential inhibitors such as meloxicam and etodolac did not exhibit any apparent action , and also , preferential COX 1 inhibitors mofezolac and indomethacin , COX 1 and COX 2 inhibitor loxoprofen sodium showed a weak effect . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 1 and COX 2 in the colonic neuromuscular layer was assessed by reverse transcription polymerase chain reaction and immunohistochemistry . ^^^ In the normal colon , indomethacin ( COX 1 / COX 2 inhibitor ) , SC 560 [ 5 ( 4 chloro phenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ] ( COX 1 inhibitor ) , or DFU [ 5 , 5 dimethyl 3 ( 3 fluorophenyl ) 4 ( 4 methylsulfonyl ) phenyl 2 ( 5H ) furanone ] ( COX 2 inhibitor ) enhanced atropine sensitive electrically evoked contractions . ^^^ In the presence of inflammation , COX 1 activity is hampered by oxidative stress , and COX 2 seems to play a predominant role in maintaining an inhibitory control of colonic neuromuscular function . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 , COX 2 or mixed inhibitors ) is most efficacious in preventing Alzheimer ' s disease . ^^^ However , the recent evidence showing an increased risk of major cardiovascular events among patients treated with certain COX 1 and COX 2 inhibitors leaves many questions unanswered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
MATERIAL AND METHODS : Mesangial cells of Cyclosporine A treated ( 4 , 7 or 10 days ) rats were obtained to evaluate mRNA expression of COX isoforms ( COX 1 , constitutive and COX 2 , inducible ) by `` in situ ' ' hybridization . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To test for possible paracrine / autocrine effects of locally produced PGF2alpha , luteal expression of the key rate limiting enzymes in prostaglandin biosynthesis , i . e . cyclooxygenase 1 and 2 ( Cox 1 and Cox 2 ) , was examined in dogs during diestrus , including the periods of CL formation , as well as early and late CL regression . ^^^ On the mRNA level , expression of Cox 1 and Cox 2 was tested by qualitative and quantitative , Real Time ( Taq Man ) RT PCR ; on the protein level , expression of Cox 2 was studied by immunohistochemistry . ^^^ The mRNA for Cox 1 and Cox 2 were detected at all stages of diestrus . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
EPA also inhibited UV induced cyclooxygenase 2 ( COX 2 ) expression without altering COX 1 expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Work in the past 15 years has shown that COX exists in two forms : COX 1 , which is largely associated with physiological functions , and COX 2 , which is largely associated with pathological functions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
On the other hand , the administration of LPS stimulated the production of prostaglandin E2 / prostaglandin F2alpha and augmented the expression of COX 1 1 h after the treatment and of COX 2 2 h post treatment . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : Mechanical strain significantly increased mRNA expression of COX 1 , COX 2 , PGD ( 2 ) synthase and peroxisome proliferator activated receptor ( PPAR ) gamma 1 , but not of PPARgamma 2 as compared to control unstretched cells ( p < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The purpose of this study was to determine COX 1 and COX 2 expression and antitumor effects of COX inhibitors in human TCC cell lines ( HT 1376 , RT 4 , and UMUC 3 cells ) and xenografts derived from those cell lines . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A group of 1 , 3 diarylprop 2 yn 1 ones ( 13 , 17 , 23 , 26 and 27 ) possessing a C 3 p SO2Me COX 2 pharmacophore were designed , synthesized and evaluated as potential dual inhibitors of cyclooxygenase 1 / 2 ( COX 1 / 2 ) and 5 / 15 lipoxygenases ( 5 / 15 LOX ) that exhibit vivo antiinflammatory and analgesic activities . ^^^ A related dual COX 1 / 2 and 5 / 15 LOX inhibitor 3 ( 4 methanesulfonylphenyl ) 1 ( 4 cyanophenyl ) prop 2 yn 1 one ( 13g , COX 1 IC 50 = 31 . 5 microM ; COX 2 IC 50 = 1 . 0 microM ; SI = 31 . 5 ; 5 LOX IC 50 = 1 . 0 microM ; 15 LOX IC 50 = 3 . 2 microM ) exhibited more potent antiinflammatory activity ( ED 50 = 90 mg / kg ) , being superior to the reference drug aspirin ( ED 50 = 129 mg / kg ) . ^^^ Within this group of compounds 3 ( 4 methanesulfonylphenyl ) 1 ( 4 isopropylphenyl ) prop 2 yn 1 one ( 13e ) emerged as having an optimal combination of in vitro COX 1 / 2 and 5 / 15 LOX inhibitory effects ( COX 1 IC 50 = 9 . 2 microM ; COX 2 IC 50 = 0 . 32 microM ; SI = 28 ; 5 LOX IC 50 = 0 . 32 microM ; 15 LOX IC 50 = 0 . 36 microM ) in conjunction with a good antiinflammatory activity ( ED 50 = 35 mg / kg ) compared to the reference drug celecoxib ( ED 50 = 10 . 8 mg / kg ) when administered orally . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenases 1 and 2 ( Cox 1 and Cox 2 ) are two distinct isoforms that catalyze the conversion of arachidonic acid to prostaglandins . ^^^ The role of Cox 2 in a variety of cancers is well recognized , but the contribution of Cox 1 remains much less explored . ^^^ We have previously shown that human epithelial ovarian tumors have increased levels of Cox 1 , but not Cox 2 . ^^^ We found that these three models , which produce spontaneous EOC , also show up regulated expression of Cox 1 , but not Cox 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In conclusion , both COX 1 and COX 2 selective inhibitors constrict fetal DA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mRNA expression of COX 2 was significantly increased in endothelial cells infected with R . rickettsii and R . conorii , while that of COX 1 remained unaffected . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Molecular dynamics simulations of arachidonic acid complexes with COX 1 and COX 2 : insights into equilibrium behavior . ^^^ We have used molecular dynamics ( MD ) simulations to investigate the equilibrium behavior of both COX 1 and COX 2 enzyme isoforms with bound arachidonate . ^^^ The detailed comparisons for COX 1 versus COX 2 active site structural fluctuations may also provide useful information for design of new isozyme selective inhibitors . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Molecular dynamics simulations of arachidonic acid derived pentadienyl radical intermediate complexes with COX 1 and COX 2 : insights into oxygenation regio and stereoselectivity . ^^^ The two cyclooxygenase enzymes , COX 1 and COX 2 , are responsible for the committed step in prostaglandin biosynthesis and are the targets of the nonsteroidal antiinflammatory drugs aspirin and ibuprofen and the COX 2 selective inhibitors , Celebrex , Vioxx , and Bextra . ^^^ Herein we describe the results of explicit , 10 ns molecular dynamics simulations of both COX 1 and COX 2 with the substrate derived pentadienyl radical intermediate bound in the active site . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , we examined the effect of naproxen ( non selective COX inhibitor having much potency towards COX 1 isoform ) or rofecoxib ( a selective COX 2 inhibitor ) in subchronic immobilization stress . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 contribute differentially to the LPS induced release of PGE 2 and TxA 2 in liver macrophages . ^^^ Resident liver macrophages express substantial amounts of COX 1 , TxAS , cPGES and mPGES 2 , small amounts of COX 2 but almost no detectable amounts of mPGES 1 . ^^^ LPS induces an increase of COX 2 and mPGES 1 , but does not change COX 1 , cPGES , mPGES 2 and TxAS at protein level . ^^^ It is concluded that ( 1 ) COX 1 and COX 2 are involved in the LPS induced synthesis of TxA 2 and PGE 2 ; ( 2 ) TxA 2 release is catalyzed at early time points by the combined action of COX 1 and TxAs , whereas at later time points the newly expressed COX 2 couples to TxAS and contributes to the TxA 2 release ; ( 3 ) PGE 2 release within the first 8 h is predominantly catalyzed by COX 2 , whereas at later time points COX 1 couples to the newly expressed mPGES 1 and contributes to the PGE 2 release . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The present study aimed to determine the effects of COX 1 and COX 2 gene disruption on Helicobacter pylori induced gastric inflammation . ^^^ METHODS : Wild type ( WT ) , COX 1 and COX 2 heterozygous ( COX 1+ / and COX 2+ / ) , and homozygous COX deficient ( COX 1 / and COX 2 / ) mice were inoculated with H . pylori strain TN 2 and killed after 24 weeks of infection . ^^^ In the presence of H . pylori infection , apoptosis was increased in both WT and COX deficient mice , whereas cell proliferation was increased in WT and COX 1 deficient , but not in COX 2 deficient , mice . ^^^ Prostaglandin E 2 levels were increased in infected WT and COX 2 deficient mice but were at very low levels in infected COX 1 deficient mice . ^^^ COX 2 , but not COX 1 , deficiency suppresses H . pylori induced cell proliferation . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of cannabinoid receptors , CB 1 and CB 2 ; cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) ; inducible nitric oxide synthase ( iNOS ) ; as well as activation of nuclear factor kappa B ( NF kappaB ) in chondrocytes were studied using immunoblotting techniques and immunofluorescence . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The COX 1 and COX 2 activity participated in the production of PGE ( 2 ) triggered by exogenous PGE ( 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The effects induced by a selective COX 2 inhibitor ( SC 236 ) were compared with those of a nonselective COX 1 and 2 inhibitor ( indomethacin ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Moreover , the COX 2 / COX 1 selectivity ratio is vital in the design of COX 2 inhibitory drugs , as it is clear from rofecoxib , which is more than 50 fold COX 2 selective . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : IL 1beta , H ( 2 ) O ( 2 ) , TNF alpha , TNF alpha + H ( 2 ) O ( 2 ) , or A2E stressed ARPE 19 or HN cells displayed no significant upregulation in COX 1 or COX 3 RNA message abundance ; however , significant upregulation was observed in COX 2 RNA message and protein abundance . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mean change for Cox 1 was 0 . 21 [ 95 % confidence interval ( 95 % CI ) , 0 . 44 to 0 . 01 , P = 0 . 06 ] and for Cox 2 was 0 . 31 ( 95 % CI , 0 . 55 to 0 . 08 , P = 0 . 01 ) . ^^^ Patients in the radiation therapy group exhibited a significant decrease compared with the nonradiated group ( P = 0 . 03 for Cox 1 ; P = 0 . 05 for Cox 2 ) . ^^^ In addition , significant decreases in Cox 1 ( 0 . 71 ; 95 % CI , 1 . 17 to 0 . 25 , P = 0 . 005 ) and Cox 2 ( 0 . 65 ; 95 % CI , 1 . 17 to 0 . 13 , P = 0 . 02 ) were found in never smoking patients but not in former or current smokers . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Basal myofibroblast COX 1 and COX 2 expression was downregulated in Gi alpha 2 / cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 / 2 selective inhibition by the hop extract was investigated in a COX 1 whole blood assay ( WBA ) and a COX 2 WBA . ^^^ Furthermore , hop extract showed a decline in PGE ( 2 ) production in the COX 2 whole blood assay ( WBA ) with an IC ( 50 ) of 20 . 4 microg / mL , while in the COX 1 WBA no inhibition of PGE ( 2 ) production was observed . ^^^ The COX 1 inhibitor SC 560 inhibited PGE ( 2 ) production in the COX 1 WBA but not in the COX 2 WBA . ^^^ At 2 microM , celecoxib inhibited PGE ( 2 ) production in the COX 2 WBA by 92 % and in the COX 1 WBA by 50 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the role of cyclooxygenase ( COX ) isozymes ( COX 1 and 2 ) in the regulation of bladder volume capacity ( BVC ) in several rat urodynamic models , using a selection of nonsteroidal anti inflammatory drugs ( NSAIDs ) , some selective for COX 2 , correlating the potency of the tested compounds in the urodynamic models and their in vitro potency as inhibitors of COX isozymes , to verify the relative importance of the different isozymes . ^^^ The potency of the compounds in the cystometry model with bladders infused with acetic and in the isovolumic bladder voiding contractions correlated well with COX 2 inhibition , but not COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There were also three fold more cells expressing 5 LO ( p=0 . 037 ) , with no differences in 5 LO activating protein ( FLAP ) , COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Real time PCR analysis showed that ethanol had no effect on the expression of cyclooxygenase 1 ( COX 1 ) , but blocked ( p < 0 . 01 ) FSH stimulated expression of COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Three primary COX isoenzymes are distinguished : COX 1 ( constitutive ) , COX 2 ( inducible ) , and COX 3 , which is detected mainly in the central nervous system . ^^^ A number of partial forms of COX 1 and COX 2 are also known , but their biological functions have not been well evaluated . ^^^ In contrast to the COX 1 gene , whose expression is typical for most of the cells , constant COX 2 expression was detected in the placenta and fetal tissue in late pregnancy . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The latter cells also express the main biosynthetic enzymes involved in PG production , cytosolic phospholipase A 2 ( PLA 2 ) , COX 1 and COX 2 , PGF synthase and PGE synthase and the corresponding EP 2 , EP 3 , EP 4 and FP receptors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are two cyclooxygenase ( COX ) genes encoding characterized enzymes , COX 1 and COX 2 . ^^^ The objective of this study was to determine the effect of COX 1 or COX 2 gene disruption on the development of chronic Freund ' s adjuvant induced arthritis and inflammatory pain in male and female mice . ^^^ The effect of COX 1 or COX 2 gene disruption on inflammatory hyperalgesia , allodynia , inflammatory edema , and arthritic joint destruction was studied . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Profiling of eicosanoid production in the rat hippocampus during kainic acid induced seizure : dual phase regulation and differential involvement of COX 1 and COX 2 . ^^^ These results suggest that KA signals directly stimulate the arachidonic acid cascade in the initial phase and that COX 1 and COX 2 , both constitutively expressed at low levels , differentially contribute to PG productions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Short term exposure ( 30 min ) resulted in a small but significant amount of PGE 2 release which was mainly inhibited by a selective COX 1 inhibitor , SC 560 but only partially by a selective COX 2 inhibitor , NS 398 , and did not induce COX 2 protein as determined by Western blotting . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A number of novel indomethacin glycolamide esters were synthesized and tested for their cyclooxygenase ( COX 1 and COX 2 ) inhibition properties in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PIOX is a member of a larger family of fatty acid alpha dioxygenases that includes the mammalian cyclooxygenase enzymes cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PGE 2 biosynthesis is controlled by cyclooxygenase 1 ( COX 1 ) and COX 2 , whose induction involves the STATs . ^^^ Pharmacologic experiments showed that PGE 2 production is dependent on newly synthesized COX 2 , but COX 1 protein . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Furthermore , curcumin decreased the levels of COX 2 mRNA and protein expression without significant changes in the levels of COX 1 , which correlated with a decrease in prostaglandin E 2 ( PGE 2 ) synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We investigated the effects of the aspirin metabolite , salicylate ( SA ) , on 7 , 12 dimethylbenz [ a ] anthracene ( DMBA ) DNA adduct formation as well as on the expression of the enzymes involved in the carcinogen bioactivation pathway , in particular cytochrome P 450 1A ( CYP1A ) and cyclooxygenases ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibition of COX 2 , but not COX 1 , attenuated the cyclic stretch induced PG increase in the media , suggesting that cyclic stretch primarily affected PG synthesis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Additional rats received Pio ( 10 mg . kg 1 . day 1 ) for 3 days and intravenous SC 58125 [ a cyclooxygenase 2 ( COX 2 ) inhibitor ] or SC 560 ( a COX 1 inhibitor ) 15 min before ischemia . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 were determined by immunohistochemistry and reverse transcriptase polymerase chain reaction , and mucosal prostaglandin E ( 2 ) levels by enzyme linked immunosorbent assay . ^^^ COX 1 and COX 2 expression , as well as mucosal prostaglandin E ( 2 ) levels were not influenced by H . pylori status and aspirin medication . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Despite having conserved amino acid sequences , cox 1 , cox 2 , cox 3 , and cob have the fastest mean rates of nucleotide substitution , and the greatest variation in rates , whereas rrnS and rrnL have the slowest rates . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
LPS increased COX 2 but not COX 1 expression . ^^^ LPS induced gastric luminal fluid accumulation was negated by both nonselective COX inhibition with salicylate and selective COX 2 inhibition with NS 398 but not by selective COX 1 inhibition with SC 560 . ^^^ LPS induced gastroprotection does not depend entirely on accumulation of luminal fluid and is independent of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , the effects of this CLX treatment on tumor and adjacent mucosa expression of gastrin , its receptors ( CCK 2 ) , and COX 1 and COX 2 , as well as protein expression of the active form of nuclear factor kappa B ( NFkappa B ) and the apoptotic related proteins Bcl 2 and survivin , have been examined . ^^^ The gene or protein expressions of progastrin , gastrin , CCK 2 , COX 1 , COX 2 , Bcl 2 , and survivin as well as NFkappa B were determined by RT PCR or Western blot in biopsy samples of tumor and intact mucosa of CRC patients . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After treatment of 12 hours , low dose GM CSF ( 0 . 001 0 . 1 ng / mL ) increased COX 2 mRNA levels in stromal cell , whereas high dose GM CSF ( 1 100 ng / mL ) decreased COX 1 and COX 2 mRNA levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In order to clarify whether COX inhibitors directly inhibit A 549 cell , three COX inhibitors , NS 398 ( selective COX 2 inhibitor ) , SC 560 ( selective COX 1 inhibitor ) , and acetyl salicylic acid ( ASA , non selective COX inhibitor ) , were studied . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In vitro experiments revealed that curcumin inhibited Cox 2 levels , but promoted those of Cox 1 in colo 205 cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mRNA levels of cPLA 2 , COX 2 and mPGES 1 in the bladder papilloma and TCC were significantly higher than those in normal bladder ( P < 0 . 01 ) , while the mRNA levels of COX 1 and mPGES 2 in TCC were unchanged compared with normal bladder . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These findings demonstrate that COX 1 and COX 2 derived prostanoids contribute importantly to the development of malignant hypertension in Cyp1a1 Ren 2 transgenic rats . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In this study , we show that COX 2 was abolished in the distal end of the vas deferens in neonatally estrogenized ( diethylstilbestrol , NeoDES ) Sprague Dawley ( SD ) rats at age of 15 mo , but the control normal rats were found to remain constitutive expression at the same age , while the levels of COX 1 in these rats remained intact . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
IL 1beta increased the mRNA expression and activity of COX 2 , and production of PGE ( 2 ) in a dose and time dependent manner in RCMEC , while mRNA and activity of COX 1 were not significantly altered . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Targeted deletion of the gene encoding mPGES 1 led to a 3 . 2 fold decrease in LPS stimulated PGE ( 2 ) release by cardiomyocytes in comparison with wild type cells but had no effect on COX 1 , COX 2 , mPGES 2 , or cytosolic PGES mRNA levels . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs , which inhibit the activity of COX 1 and COX 2 , decrease AAA expansion in humans and animal models of the disease . ^^^ In the current study , we investigated the effectiveness of selective inhibition of COX 1 or COX 2 in attenuating AAA formation . ^^^ METHODS AND RESULTS : Eight week old male apolipoprotein E deficient mice were treated with selective inhibitors of COX 1 or COX 2 , SC 560 ( approximately 25 mg . kg ( 1 ) . day ( 1 ) ) , or celecoxib ( approximately 125 mg . kg ( 1 ) . day ( 1 ) ) , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A role for COX isoforms in the mediation of the responses was assessed by use of valeryl salicylate ( 3 mM ) and NS 398 ( 10 microM ) , inhibitors of COX 1 and COX 2 , respectively . ^^^ In WT arterioles , inhibition of COX 2 did not significantly affect FID , whereas inhibition of COX 1 decreased the dilation by approximately 57 % . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Here we investigate the role of the cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) isoforms in post operative duodenal ileus . ^^^ The selective COX 1 inhibitor SC 560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity induced increase in mucosal permeability was smaller than in COX 2 inhibited animals . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
A group of regioisomeric phenylethynylbenzenesulfonamides possessing a COX 2 SO2NH2 pharmacophore at the para , meta or ortho position of the C 1 phenyl ring , in conjunction with a C 2 substituted phenyl ( H , OMe , OH , Me , F ) group , were synthesized and evaluated as inhibitors of the cyclooxygenase 1 ( COX 1 ) and cyclooxygenase 2 ( COX 2 ) isozymes . ^^^ In vitro COX 1 / 2 isozyme inhibition structure activity data showed that COX 1 / 2 inhibition and the COX selectivity index ( SI ) are sensitive to the regioisomeric placement of the COX 2 SO2NH2 pharmacophore where the COX 2 potency order for the benzenesulfonamide regioisomers was generally meta > para and ortho . ^^^ Among this group of compounds , the in vitro COX 1 / 2 isozyme inhibition studies identified 3 ( 2 phenylethynyl ) benzenesulfonamide ( 10a ) as a COX 2 inhibitor ( COX 2 IC50=0 . 45 microM ) with a good COX 2 selectivity ( COX 2 SI=70 ) . ^^^ In contrast , 2 [ 2 ( 3 fluorophenyl ) ethynyl ] benzenesulfonamide ( 11c ) possessing a SO2NH2 COX 2 pharmacophore at the ortho position of the C 1 phenyl ring exhibited COX 1 inhibition and selectivity ( COX 1 IC50=3 . 6 microM ) . ^^^ Similar docking of 10a within the COX 1 binding site shows that the meta SO2NH2 pharmacophore is unable to interact with the respective amino acid residues in COX 1 that correspond to those near the secondary pocket in COX 2 due to the presence of the larger Ile 523 in COX 1 that replaces Val 523 in COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The increase in PGE ( 2 ) was blocked by SB 203580 , AACOCF 3 , BEL , and the COX 2 inhibitor NS 398 but not by PD 98059 or the COX 1 inhibitor valeryl salicylate . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To determine cellular expression , frozen sections of rat tibial growth plate and primary chondrocyte cultures were stained using immunohistochemistry with polyclonal antibodies directed towards COX 1 , COX 2 , EP 1 , EP 2 , EP 3 , and EP 4 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Analysis of thromboxane B ( 2 ) ( TxB ( 2 ) ) secretion from whole blood either stimulated via the COX 1 or COX 2 pathway revealed that cardamonin inhibits the generation of TxB ( 2 ) via both pathways with IC ( 50 ) values of 2 . 9 and 1 . 1 microM , respectively . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA did not differ between any groups at 5 d . ^^^ Additionally , OL induced a 20 fold increase in COX 2 mRNA expression compared with NL ( P < 0 . 05 ) at 14 d , without affecting COX 1 mRNA level . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Three cyclooxygenase ( COX ) isoenzymes are involved in prostaglandin biosynthesis , COX 1 , COX 2 and a recently discovered splice variant of COX 1 , COX 3 . ^^^ We compared the antinociceptive action of paracetamol with the non selective non steroid anti inflammatory drug , diclofenac and studied paracetamol antinociception in COX 1 and COX 2 knockout mice . ^^^ COX 1 , COX 2 and COX 3 enzyme proteins were expressed in the same brain regions . ^^^ The effects of paracetamol on writhing responses and on brain PGE ( 2 ) levels were reduced in COX 1 , but not COX 2 , knockout mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Selective COX 2 inhibitors reduce the risk of GI side effects , and although they inhibit platelet COX 1 , it is to a far lesser extent than COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
After UNX , renal cortical protein expression of cytochrome P 450 2c23 isoform ( CYP2c23 ) and cyclooxygenase 1 ( COX 1 ) was unaltered , but it was decreased for CYP4a and increased for COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) metabolites were suggested to be involved in this lymphatic dysfunction , since application of nonselective COX inhibitor ( 10 microM indomethacin ) or a combination of COX 1 and COX 2 inhibitors ( 1 microM SC 560 and 10 microM celecoxib ) markedly increased constriction frequency or induced them in lymphatics from TNBS treated animals in vivo and in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expression in the RGM 1 cells was analyzed by western blotting . ^^^ RESULTS : H . pylori did not affect COX 1 expression ; whereas COX 2 expression increased by six fold at 24 h after incubation of RGM 1 cells with 10 microg / mL H . pylori water extracts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Antibodies against the following enzymes were also used : cyclo oxygenase ( COX 1 , COX 2 ) , 5 lipoxygenase ( 5 LO ) , 5 lipoxygenase activating factor ( FLAP ) , LTA 4 hydrolase ( LTA4h ) and LTC 4 synthase ( LTC4s ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Structure activity studies for the ( Z ) 1 ( 3 , 5 di tert butyl 4 hydroxyphenyl ) 2 ( 4 methanesulfonylphenyl ) 1 phenylalk 1 ene regioisomers showed that COX 1 inhibition decreased , COX 2 inhibition increased , and the COX 2 selectivity index ( SI ) increased as the chain length of the alkyl substituent attached to the olefinic double bond was increased ( Et > n butyl > n heptyl ) . ^^^ Compound 9c is of particular interest since it also exhibits a dual inhibitory activity against the COX ( COX 1 IC50=3 . 0 microM , and COX 2 IC50=0 . 36 microM , COX 2 SI=8 . 3 ) isozymes . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While the expression of COX 1 remained constitutive , mRNA and protein levels of COX 2 were up regulated by treatment with PMA . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : To better understand the molecular responses to COX inhibition , we analyzed the gene expression level of the genes encoding enzymes related to prostaglandin production including the COX 1 gene ( PTGS 1 ) and the COX 2 gene ( PTGS 2 ) , as well as their genetic polymorphisms , and the analgesic response to COX inhibitory drugs such as ibuprofen or rofecoxib or to placebo after minor surgery . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Chronically catheterized and instrumented fetal sheep were subjected to transient brachiocephalic occlusion ( BCO ) after intracerebroventricular injection of resveratrol ( PGHS 1 or COX 1 inhibitor ) , nimesulide ( PGHS 2 or COX 2 inhibitor ) , or vehicle . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Like in many tissues , in adult skin COX 1 is a constitutive ' housekeeping ' enzyme , while COX 2 is induced transiently in stress situations such as tissue damage and regeneration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
PURPOSE : Cyclooxygenases ( COX 1 and COX 2 ) and prostaglandins regulate angiogenesis in several settings , including cancer and ischemia . ^^^ METHODS : Mice lacking either the COX 1 ( COX 1 ( / ) ) or COX 2 isoform ( COX 2 ( / ) ) were employed in a model of oxygen induced retinopathy . ^^^ Quantitative analysis of fluorescein perfused and isolectin B 4 stained retinal angiograms at postnatal day 18 ( P 18 ) revealed similar global levels of neovascular tufts in hyperoxia treated wild type , COX 1 ( / ) , and COX 2 ( / ) mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
There are a lot data in the literature which suggest that selective COX 2 inhibitors ( rofecoxib and celecoxib ) produce the similar effects on the kidney as traditional nonsteroidal anti inflammatory drugs ( inhibitors of COX 1 and COX 2 ) . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present studies , endometrial COX 1 and COX 2 expression throughout the oestrous cycle and early pregnancy was analysed in pigs using real time reverse transcriptase polymerase chain reaction ( RT PCR ) , Western blot and immunohistochemistry . ^^^ COX 1 and COX 2 were localized in the luminal and glandular epithelium as well as in the uterine stroma . ^^^ In contrast to COX 1 , a positive immunostaining reaction for COX 2 was detected only on days 12 16 after ovulation and on days 14 16 of pregnancy . ^^^ In conclusion , these results indicate specific patterns of COX 1 and COX 2 expression in the porcine endometrium throughout the oestrous cycle and early pregnancy . ^^^ COX 2 rather than COX 1 seems to be the primary enzyme responsible for modulated PGs production at the time of luteolysis in cyclic and during implantation in pregnant animals . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CIAA selectively inhibited COX 2 activity compared with COX 1 in in vitro assays with rat whole blood . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Semi quantitive reverse transcriptase polymerase chain reaction ( RT PCR ) was performed to measure the levels of COX 1 mRNA and COX 2 mRNA in the thoracic aorta , superior mesenteric artery ( SMA ) , and small intestine of IHPH , PHPH and SO rats , respectively . ^^^ The expression of COX 1 mRNA in the thoracic aorta , SMA and small intestine was enhanced , whereas COX 2 mRNA expression was not detected in either of these vessels or the small intestine . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin ( 2 mg / kg ) , 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ( SC 560 ; COX 1 inhibitor ; 3 mg / kg ) , and rofecoxib ( COX 2 inhibitor ; 3 mg / kg ) were given p . o . once daily for 6 days , during the first 3 days or last 3 days of the experimental period . ^^^ In conclusion , endogenous PGs play a role in the healing of intestinal ulcers through EP 4 receptors , yet the COX isozyme involved differs depending on the stage of healing ; COX 2 in the early stage and COX 1 in the late stage . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Platelet cyclooxygenase 1 ( COX 1 ) and COX 2 mRNA and protein expression were without significant differences between the two groups . ^^^ In conclusion , AR appears to be unrelated to differences in platelet COX 1 and COX 2 expression or to a novel platelet COX 1 SNP and the PlA ( 1 ) / A ( 2 ) SNP . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULT : COX 1 and COX 2 were inhibited by slenderstyle acanthopanax root bark , and the inhibitive rate of COX 2 was higher than that of COX 1 at the same concentration . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We describe and compare four methods for evaluating the expression of estrogen receptors alpha / beta and COX 1 and COX 2 in desmoid tumor derived cells and tissues : immunocytochemistry , immunohistochemistry , RT PCR , and two color Western blot detection with the Odyssey infrared imaging system . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 expressions were measured by Western blot analysis . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , pretreatment of HEY and OVCA 433 ovarian carcinoma cell lines with green tea and EGCG inhibited ET 1 / ET ( A ) R expression , ET ( A ) R mediated COX 1 / 2 mRNA expression , and COX 2 promoter activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Because PGE 2 has anti inflammatory , antifibrotic , and bronchodilating properties of relevance to asthma , the effect of IL 13 ( 10 ng / mL for 10 days ) on PGE 2 pathway elements in first passage air liquid interface epithelial cells from 8 endobronchial brushings ( 5 asthmatic subjects and 3 healthy subjects ) was evaluated . mRNA and protein levels for COX 1 and COX 2 , membrane bound PGE synthase 1 , 15 PG dehydrogenase , and the receptors EP 2 and EP 4 were quantified by means of real time PCR and Western blotting . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
RESULTS : COX 1 was expressed in the cytoplasm and COX 2 was distributed mainly near the nuclear membrane of osteoclasts . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These activities include inhibiting activity of cox 1 , cox 2 , and NF kb . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins ( PGs ) are potent proinflammatory mediators generated through arachidonic acid metabolism by cyclooxygenase 1 and 2 ( COX 1 and COX 2 ) in response to different stimuli and play an important role in modulating the inflammatory responses in a number of conditions , including allergic airway inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis revealed that endothelium denuded abdominal aortas express COX 2 , but not COX 1 , and that expression of COX 2 was significantly increased in eNOS ( / ) compared with WT mice . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Intracerebroventricular infusion of pioglitazone , an agonist of the PPARgamma , over a 5 day period before and 2 days after MCAO , reduced the infarct size , the expression of tumor necrosis factor alpha ( TNF alpha ) , COX 2 , and the number of cells positively stained for COX 1 and COX 2 in the peri infarct cortical regions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Western blot analysis showed that COX 1 but not COX 2 protein expression was increased in aortic rings stimulated with AA from the rats fed the HF diet . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
INTERVENTIONS : Immunohistochemical techniques were used to evaluate the expression of the enzymes COX 1 , COX 2 , 5 LO , 12 LO , and 15 LO in nasal polyp tissue specimens from AS and AT patients . ^^^ Statistically significant ( P < . 05 ) differences in staining of columnar epithelium were noted for COX 1 ( basal cell layer cytoplasm ) , COX 2 ( apical cell layer cytoplasm ) , and 12 LO ( full thickness cytoplasm and nucleus ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since oxidised HDL ( Ox HDL ) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells , we investigated the effect of Ox HDL 3 on the expression of Cox 1 or Cox 2 . ^^^ Ox HDL 3 , increased Cox 2 mRNA and protein expression in endothelial cells while no effect on Cox 1 expression was observed . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 2 inhibitors , commonly referred to as coxibs , were developed to inhibit inflammatory prostanoids without interfering with production of COX 1 prostanoids . ^^^ This review article discusses beneficial and deleterious effects associated with prostanoids produced by COX 1 and COX 2 in various organs and how blockade of these products translates into clinical medicine . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Since the discovery that the anti inflammatory effects of cyclooxygenase ( prostaglandin endoperoxide H ( 2 ) synthetase ; COX ) inhibitors were dependent on their selectivity for the inducible COX 2 isoform over the constitutive COX 1 , many efforts have been devoted towards the design of compounds displaying improved COX 2 selectivity . ^^^ In order to evaluate such possible benefits , several well characterized model inhibitors were selected and docked in the murine COX 2 and COX 1 binding sites . ^^^ As in previous publications , these were found to correlate closely ( r ( 2 ) = 0 . 66 and 0 . 75 for COX 2 and COX 1 , respectively ) with experimental inhibitory activities towards the recombinant enzymes gathered from the literature . ^^^ These model compounds were theoretically modified by substituting selected carbon atoms by an sp ( 3 ) silicon , and further docked in both COX 2 and COX 1 binding sites in order to derive their predicted inhibitory activity for both isoforms . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When macrophages from COX 1 / or COX 2 / mice were treated with zymosan , 20 25 % and 10 15 % of the PG and PG G synthesis observed in wild type cells respectively was COX 2 dependent . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade , we examined the expression and activity of COX 2 and phospholipase A 2 enzymes ( cPLA 2 and sPLA 2 ) , as well as the expression of terminal prostaglandin E synthases ( cPGES , mPGES 1 , and 2 ) in wild type and COX 1 ( / ) mice . ^^^ Overall , our data suggest that COX 1 and COX 2 play a distinct role in brain PG biosynthesis , with basal PGE 2 production being metabolically coupled with COX 2 and TXB 2 production being preferentially linked to COX 1 . ^^^ Additionally , COX 1 deficiency can affect the expression of reciprocal and coupled enzymes , COX 2 , Ca2+ dependent PLA 2 , and terminal mPGES 2 , to overcome defects in brain AA cascade . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
We have demonstrated previously in mice that COX 2 inhibition enhances angiotensin 2 induced hypertension , and COX 1 inhibition attenuates the pressor effect of angiotensin 2 . ^^^ To further elucidate the mechanism underlying the functional difference of COX 1 versus COX 2 inhibition , the present studies examined the prostaglandin ( PG ) profiles derived in COX 1 or COX 2 inhibited mouse kidney and aorta using gas chromatographic / mass spectrometric assays . ^^^ At baseline , inhibition of COX 1 decreased total prostaglandins in renal cortex , medulla , and aorta , whereas COX 2 inhibition decreased total prostaglandins only in renal medulla . ^^^ Angiotensin 2 also significantly increased renal PGF2alpha in cortex , but not in medulla , through both COX 1 and COX 2 dependent mechanisms . ^^^ These studies demonstrate that although COX 1 primarily contributes to basal prostanoid production in the kidney and aorta , angiotensin 2 increases renal vasodilator prostanoids predominately via COX 2 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
For normal , bipolar , depressed , and schizophrenic subjects , COX 1 and COX 2 protein levels did not differ across region and patient populations . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Upregulation of COX 1 and COX 2 in nasal polyps in cystic fibrosis . ^^^ METHODS : The degree of mRNA and protein expression of cyclo oxygenase ( COX ) enzymes 1 ( COX 1 ) and 2 ( COX 2 ) was examined using quantitative reverse competitive polymerase chain reaction ( RT PCR ) and Western blot analysis in the nasal polyps from 10 patients with CF , nasal polyps from 10 non CF patients and 11 nasal mucosa specimens . ^^^ CONCLUSIONS : Upregulation in the expression of COX 1 and COX 2 could explain the high production of prostanoids reported in CF . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Among them , compound 8 , 4 ( 4 amino 2 methylsulfanyl phenylazo ) benzenesulfonamide , showed a potent inhibitory activity to the cyclooxygenase enzymes ( IC ( 50 ) ' s for COX 1 : 23 . 28 microM ; COX 2 : 2 . 04 microM ) , being active but less COX 2 selective than celecoxib . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Role of COX 1 and COX 2 on skin PGs biosynthesis by mechanical scratching in mice . ^^^ COX 1 was constitutively expressed and COX 2 expression was enhanced by scratching . ^^^ These results suggested that cutaneous PGD 2 could be mainly produced by COX 1 , and PGE 2 and PGI 2 could be produced by COX 1 and COX 2 , respectively , in mice . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Epithelial expression of COX isoforms in the cortex directs COX 1 to the distal convolutions and cortical collecting duct , and COX 2 to the thick ascending limb . ^^^ ANG 2 receptor blockade confirmed negative regulation of COX 2 by ANG 2 but blunted the decrease in COX 1 selectively in nonclipped kidneys . ^^^ B ( 2 ) receptor blockade reduced COX 2 induction in 2K1C but had no clear effect on COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Prostaglandins , catalyzed by the cyclooxygenases ( COX 1 and COX 2 ) from arachidonic acid , are one class of these factors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in most tissues , whereas COX 2 is inducibly expressed at the site of inflammation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Microarray analysis and enzyme linked immunosorbent assay was performed on mRNAs and culture media from AA and C derived membranes to document any differences in mRNA expression and protein production of IL 1 , IL 6 , IL 8 , IL 10 and expression of cyclooxygenase 1 ( COX 1 ) , COX 2 and 15 hydroxyprostaglandin dehydrogenase ( PGDH ) . ^^^ RESULTS : Increased mRNA expression of IL 1 , IL 8 and COX 2 in AA and IL 6 , IL 10 , COX 1 and PGDH in C were documented after LPS stimulation . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Transfection of endoglin in L6E9 myoblasts , shown previously to stimulate eNOS expression , led to downregulation of COX 2 with no change in COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Their synthesis is dependent on two cyclooxygenase ( COX ) enzymes , COX 1 and COX 2 , which are rate limiting for the production of prostaglandins ( PGs ) and thromboxanes from free arachidonic acid . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin ( 0 . 5 and 2 . 0 mg / kg ) , a non selective cyclooxygenase ( COX ) inhibitor , as well as meloxicam ( 0 . 5 mg / kg ) , a selective COX 2 inhibitor , but not FR 122047 ( 2 . 0 mg / kg ) , a selective COX 1 inhibitor , attenuated zymosan induced anorexia . ^^^ However , non selective inhibition by selective COX 1 and COX 2 inhibitors of brain PGE ( 2 ) generation upon zymosan injection does not support the role of COX 2 expressed in brain in zymosan induced anorexic response . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In the present study , we examined whether ( 1 ) obstruction changes the expression of the two cyclooxygenase ( COX ) isoforms , COX 1 and COX 2 in human and rat ureters and ( 2 ) administration of a selective COX 2 inhibitor influences the pelvic pressure change after experimental ureteral obstruction . ^^^ COX 1 , but not COX 2 mRNA , was readily detected in the normal rat ureter . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
METHODS : Cyclooxygenase activity and selectivity was determined in vitro by measuring prostaglandin E ( 2 ) ( PGE ( 2 ) ) production following incubation of varying concentrations of NSAID with human recombinant COX 1 or COX 2 and arachidonic acid . ^^^ RESULTS : Ketorolac was six times more active against COX 1 ( IC ( 50 ) = 0 . 02 microM ) than COX 2 ( IC ( 50 ) = 0 . 12 microM ) while bromfenac was approximately 32 times more active against COX 2 ( IC ( 50 ) = 0 . 0066 microM ) than COX 1 ( IC ( 50 ) = 0 . 210 microM ) . ^^^ CONCLUSIONS : Ketorolac is relatively COX 1 selective while bromfenac is potently selective for COX 2 over COX 1 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 2 enzyme , but not COX 1 , was significantly higher in animals treated with ATRA . ^^^ The mechanism of action involves an over expression of COX 2 , but not COX 1 , in dorsal and ventral horn areas of the lumbar spinal cord . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In COX enzyme inhibitory assays , ferulic and caffeic acid esters significantly inhibited both COX 1 and COX 2 enzymes . ^^^ Caffeates 5 10 ( C 4 C12 ) , inhibited COX 1 enzyme between 50 % and 90 % and COX 2 enzyme by about 70 % , whereas ferulates 15 21 ( C 3 C8 ) inhibited COX 1 and COX 2 enzymes by 85 95 % 25 microg / mL . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition by traditional NSAIDs ( for example , aspirin ) although chemopreventive have some side effects due to the role of COX 1 in maintaining the integrity of the gastric mucosa . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Indomethacin , SC 560 , and rofecoxib , selective COX 1 and COX 2 inhibitors , attenuated ghrelin induced protection that was restored by supplying the methyl analog of prostaglandin ( PG ) E ( 2 ) . ^^^ The expression of mRNA for COX 1 was unaffected by ghrelin , but COX 2 mRNA and COX 2 protein were detectable in I / R injured mucosa and further up regulated by exogenous ghrelin . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Elevated whole blood TXB 2 generation was not dependent on leukocyte count , COX 2 activity , or cigarette smoking but was plausibly a result of defective suppression of platelet COX 1 activity . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
BFT stimulation increased the expression of COX 2 , but not COX 1 , in human intestinal epithelial cells . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Expression of COX 1 and COX 2 was detected by semiquantitative RT PCR and Western blot . ^^^ Both COX 1 and COX 2 expression can be found in bone marrow derived endothelial progenitor cells in vitro . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These isolates were also examined for their inhibitory activity against COX 1 and COX 2 . ^^^ Although most compounds , except for 2 , 10 , and 12 , showed a strong inhibitory activity against COX 1 , they exhibited a moderate or weak inhibitory activity against COX 2 . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Levels of cyclooxygenase 2 ( COX 2 ) mRNA , but not those of COX 1 , were reported to be raised significantly after peripheral inflammation in the rat spinal cord . ^^^ The aim of the present study was to ascertain whether this pattern of COX 2 and COX 1 expression applies also to other pain conditions induced by surgical procedure . ^^^ Under the acute inflammation 2 and 6 hr after carrageenan injection levels of COX 2 mRNA were markedly raised ( 7 . 8 and 15 . 5 times ; P < 0 . 001 , respectively ) while spinal levels of COX 1 mRNA were not significantly altered ( n . s . ) . ^^^ In contrast , spinal levels of COX 2 mRNA were raised less markedly in a model of postoperative pain ( 4 . 9 times at 2 hr ; P < 0 . 001 and 2 . 9 times ( n . s . ) at 6 hr after surgery ) whilst levels of COX 1 mRNA in the lumbar spine were increased significantly ( 2 . 3 times ; P < 0 . 001 ) 6 hr after surgery . ^^^ The present findings indicate that expression of COX 2 mRNA in the spine is less dominant in postoperative pain than in inflammatory pain and that spinal COX 1 mRNA is upregulated in postoperative pain . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Their biosynthesis depends on cyclooxygenase isoforms , named COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide ( vehicle ) or COX 1 ( SC 560 ) or COX 2 ( NS 398 ) inhibitors . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The expression of COX 1 and COX 2 was measured with reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ IL 1beta stimulated the COX 2 but not COX 1 mRNA expression . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
When administered alone , AUDA BE decreased protein expression of COX 2 to 73 + / 6 % of control mice treated with LPS only without altering COX 1 expression and decreased PGE ( 2 ) levels to 52 + / 8 % compared with LPS treated mice not receiving any therapeutic intervention . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Confluent layers of ESMC were stimulated with 10 nM ET 1 and expression of COX 1 and COX 2 , involvement of receptors , and activation of p 38 MAPK , were examined by Western blot analysis . ^^^ Using ETA and ETB antagonists ( BQ 123 and BQ 788 , respectively ) , the contribution of the ET receptors to COX 1 and COX 2 expression induced by ET 1 was determined . ^^^ SB 202190 , a p 38 MAPK inhibitor , reduced expression of COX 2 , but not COX 1 . ^^^ COX 2 expression was upregulated only via the ETB receptor , and COX 1 expression was not affected by either antagonist . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
CONCLUSIONS : Unlike ibuprofen , celecoxib did not interfere with the inhibition of platelet COX 1 activity and function by aspirin despite a comparable suppression of COX 2 ex vivo in patients with osteoarthritis and stable ischemic heart disease . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In an OVA induced allergic airway inflammation model , comparable up regulation of COX 2 protein was observed in the lungs of allergic wild type and COX 1 Tr mice . ^^^ To eliminate the presumed confounding effects of COX 2 up regulation , COX 1 Tr mice were bred into a COX 2 null background . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
These results confirm that COX 1 , as well as COX 2 , contributes to colon carcinogenesis and that mofezolac may be a good chemopreventive agent for human colon cancer . . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
The mtDNA was extracted from the intestinal epithelial cells and amplified by polymerase chain reaction ( PCR ) with different primers of cytochrome oxidase ( COX 1 , COX 2 and COX 3 ) . ^^^ RESULTS : Hemorrhagic shock could result in the point mutagenesis in mitochondrial genome encoding cytochrome oxidase ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Inhibitors of neuronal NOS ( nNOS ) L NNA , general NOS L NAME and inducible NOS ( iNOS ) aminoguanidine , as well as inhibitors of COX 1 , piroxicam , and COX 2 , compound NS 398 were administered 15 min prior to carbachol to control or crowded rats ( 24 rats in cage for 7 , during 3 and 7 days ) . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
Using in vitro and ex vivo models of infection , we demonstrate here that R . rickettsii infection of human EC causes robust induction of COX 2 mRNA and protein expression but has no apparent effect on the constitutive COX 1 isoform . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
In addition , the blots revealed the presence of five subassemblies : three subassemblies involving the core subunit MTCO 1 but apparently no other subunits ; a subassembly containing subunits MTCO 1 , COX 4 , and COX5A ; and a subassembly containing at least subunits MTCO 1 , MTCO 2 , MTCO 3 , COX 4 , and COX5A . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
While the inhibition of COX 2 is related to anti inflammatory effects , the use of COX 1 might be associated with adverse reactions . ^^^
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA
Interacting proteins: P00395 and P00403	Pubmed	SVM Score :0.0
NA