Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
We have characterized two yeast mutants deficient in the splicing of transcripts of the mitochondrial gene for cytochrome c oxidase subunit 1 ( coxI ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The mitochondrial gene ( COXI ) encoding cytochrome c oxidase subunit 1 ( COI ) was isolated from two cytoplasmic genotypes of sorghum that synthesize different COI polypeptides . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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 ' ' ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The gene ( coxI or CoxA ) encoding subunit 1 ( COI ) of cytochrome c oxidase ( cytochrome aa 3 ) of Synechocystis PCC 6803 , Synechococcus PCC 7942 ( Anacystis nidulans R 2 ) and Nostoc PCC 8002 ( Nostoc Mac ) , was identified by heterologous hybridization of chromosomal digests with a 17 bp oligodeoxyribonucleotide ( probe C ) derived from the coxI of Paracoccus denitrificans . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The level of mRNA for cytochrome c oxidase subunit 1 ( COX 1 ) , which is encoded by mitochondrial DNA ( mtDNA ) , progressively decreased in the hippocampal CA 1 neurons of gerbils from 1 3 h of the reperfusion after 3 . 5 min of transient forebrain ischemia , and completely disappeared at 7 days . ^^^ The activity of cytochrome c oxidase ( COX ) protein also showed the early decrease in the CA 1 cells , and was followed by the reduction of the level of COX 1 DNA after 2 days . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Universality of mitochondrial RNA editing in cytochrome c oxidase subunit 1 ( coxI ) among the land plants . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Sequence analysis of these clones revealed that all isolated clones encode cytochrome c oxidase subunit 1 ( COX 1 ) , which is located in the mitochondrial DNA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The level of mRNA for cytochrome C oxidase subunit 1 ( COX 1 ) , which is encoded by mitochondrial DNA ( mtDNA ) , progressively deceased in the hippocampal CA 1 neurons of gerbils from 3 hours of the reperfusion after 3 . 5 min of transient forebrain ischemia , and completely disappeared at 7 days . ^^^ The activity of cytochrome C oxidase ( COX ) protein also showed the early decrease in the CA 1 cells , and was followed by the reduction of the level of COX 1 DNA after 2 days . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This study was designed to examine the effect of perinatal hypothyroidism on ontogenic change in cytochrome c oxidase subunit 1 ( COX 1 ) gene expression in the rat cerebellum by using quantitative in situ hybridization histochemistry ( ISH ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The sequence of a representative mitochondrial gene COXI , encoding cytochrome c oxidase subunit 1 , was determined in five species that cover all the orders of the Prymnesiophyta with the exception of the Pavlovales . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
An out of frame mutation of the mitochondrial DNA encoded subunit 1 of cytochrome c oxidase ( COX ) was discovered during investigation of a severe isolated muscle COX deficiency in a patient with motor neuron like degeneration . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The synthesis of mitochondrially encoded cytochrome c oxidase subunit 1 ( CoxI ) and cytochrome b ( Cob ) is impaired in pim 1 mutants containing mtDNA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The level of mRNA for cytochrome c oxidase subunit 1 ( COX 1 ) , which is encoded by mitochondrial DNA ( mtDNA ) , progressively decreased in the hippocampal CA 1 neurons of gerbils from 1 to 3 h of the reperfusion after 3 . 5 min of transient forebrain ischemia , and completely disappeared at 7 days . ^^^ The activity of cytochrome c oxidase ( COX ) protein also showed the early decrease in the CA 1 cells , and was followed by the reduction of the level of COX 1 DNA after 2 days . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Upon surveying the cytochrome c oxidase subunit 1 ( COXI ) gene of green algae , we found group 1 introns in three species of algae , Chlorella vulgaris ( Cv ) , Scenedesmus quadricauda ( Sq ) and Protosiphon botryoides ( Pb ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
For the comprehensive analyses of deviant codes in protistan mitochondria ( mt ) , we sequenced about a 1 . 1 kb region of a mitochondrial ( mt ) gene , the cytochrome c oxidase subunit 1 ( coxI ) in two chlorarachniophytes , the filose amoeba Euglypha rotunda , the cryptomonad Cryptomonas ovata , the prymnesiophyte ( haptophyte ) Diacronema vlkianum ( Pavlovales ) , and the diatom Melosira ambigua . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The level of mRNA for cytochrome c oxidase subunit 1 ( COX 1 ) progressively decreased in CA 1 neurons after a transient ischemia and completely disappeared at 7 days . ^^^ The activity of cytochrome c oxidase ( COX ) protein also showed an early decrease in CA 1 cells and was followed by a reduction in the level of COX 1 DNA after 2 days . 5 . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In order to address the relationships among diatom groups and to investigate possible changes in their mitochondrial ( mt ) genetic codes , we have analyzed a 1 . 1 kb region of the cytochrome c oxidase subunit 1 ( coxI ) gene from eight diverse diatom species . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Phylogenetic analyses carried out on cytochrome c oxidase ( COX ) subunit 1 mitochondrial genes from 14 primates representing the major branches of the order and four outgroup nonprimate eutherians revealed that transversions and amino acid replacements ( i . e . , the more slowly occurring sequence changes ) contained lower levels of homoplasy and thus provided more accurate information on cladistic relationships than transitions ( i . e . , the more rapidly occurring sequence changes ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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 P20674	Pubmed	SVM Score :0.0
A panel of 35 human and animal cell lines , whose species of origin were previously confirmed by isoenzyme assay , was studied with nine species specific primer pairs that specifically anneal to DNA sequences codifying for human , cat , dog , mouse , rat , horse , rabbit , African Green monkey cytochrome c oxidase subunit 1 ( cox 1 ) , and one primer pair specific for the cytochrome b gene of Chinese hamster . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Part of the cytochrome c oxidase subunit 1 gene ( p cox 1 ) was amplified by PCR , scanned for sequence variation by single strand conformation polymorphism ( SSCP ) , and representative samples from different host species were selected for DNA sequencing . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Antibodies to 2 methyl 3 hydroxybutyryl CoA dehydrogenase ( MHBD ) and cytochrome c oxidase subunit 1 ( COX 1 ) were used as a reference . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Partial sequences of the cytochrome c oxidase subunit 1 ( cox 1 ) , ribosomal internal transcribed spacer region 2 ( ITS 2 ) and the large subunit 28S rDNA gene were obtained and analysed using pairwise distance matrices and parsimony methods in order to characterise the interrelationships between 14 isolates of four nominal species of Glypthelmins recognised on morphological grounds . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Using quantitative polymerase chain reaction , mitochondrial to nuclear DNA ratios were determined by quantification of cytochrome c oxidase subunit 1 ( CoxI ) and beta actin genes . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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 P20674	Pubmed	SVM Score :0.0
In this study , we exploited the high resolution capacity of PCR coupled single strand conformation polymorphism ( SSCP ) to screen for sequence variation in part of the cytochrome c oxidase subunit 1 gene ( p cox 1 ) among individuals of the parasitic nematode , Oesophagostomum bifurcum from human or Mona monkey hosts from Africa . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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 P20674	Pubmed	SVM Score :0.0
The mitochondrial encoded cytochrome c oxidase subunit 1 ( COXI ) transcript level and cytochrome c oxidase ( COX ) activity were measured by RT PCR and histochemical methods respectively . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A cytochrome c oxidase subunit 1 gene ( COXI ) was identified and isolated as a differentially expressed gene between insecticide susceptible ACY and resistant Apyr R German cockroach strains using PCR selected subtractive hybridization and cDNA array techniques . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This is paralleled by a reduction in the amount of the mitochondrial marker enzyme cytochrome c oxidase subunit 1 ( COXI ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
STUDY OBJECTIVES : Increased mRNA level of subunit 1 cytochrome c oxidase ( COXI ) during wakefulness and after short term sleep deprivation has been described in brain . ^^^ ABBREVIATIONS : ADP , adenosine diphosphate ; ATP , adenosine triphosphate ; COXI , cytochrome c oxidase subunit 1 mRNA ; COX , cytochrome c oxidase ( protein ) ; CREB , cyclic AMP response element binding protein ; DNA , deoxyribonucleic acid ; EDTA , ethylenediaminetetraacetic acid ; EEG , electroencephalography ; EMG , electromyography ; GABP , GA binding protein ; HEPES , 4 ( 2 hydroxyethyl ) piperazine 1 ethanesulfonic acid ; mRNA , messenger ribonucleic acid ; NADH , nicotinamid adenine dinucleotide , reduced ; NDII , NADH dehydrogenase subunit 2 mRNA ; NRF , nuclear respiratory factor . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Mitochondrial DNA ( mtDNA ) mutations associated with rhabdomyolysis are rare but have been described in sporadic cases with mutations in the cytochrome b and cytochrome c oxidase ( COX ) genes and in 3 cases with tRNALeu mutation . ^^^ We report a novel heteroplasmic G6708A nonsense mutation in the mtDNA COI gene encoding COX subunit 1 in a 30 year old woman with muscle weakness , pain , fatigue , and one episode of rhabdomyolysis . ^^^ Western blot analysis and immunohistochemical staining revealed that reduced levels of COX subunit 1 were accompanied by reduced levels of other mtDNA encoded subunits , as well as nuclear DNA encoded subunit 4 , supporting the concept that COX subunit 1 is essential for the assembly of complex 4 in the respiratory chain . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This study investigated genetic variability within the ' eyeworm ' Thelazia callipaeda ( Nematoda : Thelazioidea ) from Europe and Asia by polymerase chain reaction ( PCR ) coupled sequencing and mutation scanning of the mitochondrial cytochrome c oxidase subunit 1 gene ( cox 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Further analysis on natural selection indicated that the COXI ( cytochrome c oxidase subunit 1 ) gene was under positive selection in P . hodgsonii and Bos grunniens . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
MAIN OUTCOME MEASURE ( S ) : Comparison of the RNA expression levels of genes including cytochrome c oxidase subunit 1 ( COX 1 ) , adenosine triphosphate synthase 6 ( ATPase 6 ) , flavoprotein , and succinate ubiquinone oxidoreductase , and protein levels of COX 1 and flavoprotein in different calcium ion treatment groups . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
For this purpose , on gestational days 11 , 12 and 13 we studied the mitochondrial DNA ( mtDNA ) content and the relative gene expression of proteins involved in mtDNA replication ( mitochondrial single strand DNA binding protein ( mtSSB ) ) , mtDNA transcription ( mitochondrial transcription factor A ( TFAM ) ) , as well as in mitochondrial function ( cytochrome c oxidase subunit 1 ( COXI ) ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We do so using small subunit ( SSU ) and large subunit ( LSU ) ribosomal DNA and cytochrome c oxidase subunit 1 ( cox 1 ) sequences . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The specific and the total activities of this enzyme , as well as those of cytochrome oxidase ( COX ) ( EC 1 . 9 . 3 . 1 ) in IBAT increase up to at least 20 days of age . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Subunit VIIa of mammalian cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) exists in at least two isoforms , one present in all tissue types ( ' liver ' isoform ; COX VIIa L ) and the other specific for cardiac and skeletal muscle ( COX VIIa M ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Subunit VIa of mammalian cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) exists in two isoforms , one present ubiquitously ( ' liver ' isoform ; COX VIa L ) and the other present only in cardiac and skeletal muscle ( COX VIa M ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Subunit Vb of mammalian cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) is encoded by a nuclear gene and assembled with the other 12 COX subunits encoded in both mitochondrial and nuclear DNA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have isolated a chimpanzee processed pseudogene for subunit 4 of cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) by screening a chimpanzee genomic library in lambda Charon 32 with a bovine liver cDNA encoding COX subunit 4 ( COX 4 ) , and localized it to a 1 . 9 kb HindIII fragment . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have isolated a full length human liver cDNA clone specifying the nuclear encoded subunit 4 of the human mitochondrial respiratory chain enzyme , cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Using in situ hybridization and immunocytochemistry , we studied a muscle biopsy sample from a patient with Kearns Sayre syndrome ( KSS ) who had a deletion of mitochondrial DNA ( mtDNA ) and partial deficiency of cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have isolated a full length human fetal muscle cDNA clone specifying the nuclear encoded subunit Vb of the human mitochondrial respiratory chain enzyme , cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) , and a partial length brain cDNA clone specifying the analogous bovine subunit . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
An approach is described here whereby the control of respiration by cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) was analyzed in intact cultured human osteosarcoma 143B . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cytochrome c oxidase ( COX , EC 1 . 9 . 3 . 1 ) , the last component of the mitochondrial electron transfer chain , is built up by 13 polypeptides ; 3 of them are encoded by the mitochondrial genome while the 10 smaller subunits are encoded by the nuclear genome . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The mtDNA encoded cytochrome c oxidase subunit 1 ( COX 1 ) protein level was identical to control in nephrosis phase , however , a 45 % reduction was seen in FSGS phase . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Determination of cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) activity in human mitochondria presents several technical difficulties which result in a large intra and interlaboratory variability , especially when a single wavelength spectrophotometer ( SWS ) is used , as is generally done in most laboratories in the context of screening procedures for the detection of respiratory chain deficiencies . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have now studied the effects of a 7 day treatment with acetyl L carnitine ( ALCAR ) in the spf / Y mice on the activity and expression of the respiratory chain enzyme cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
More particularly , in K562 / R0 . 5 cells cytochrome c ( cyt c ) oxidase ( COX ; EC 1 . 9 . 3 . 1 ) activity and cytochrome aa 3 content dramatically decreased since cells enter into the stationary phase . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Whatever the tissue , citrate synthase ( CS , EC 4 . 1 . 3 . 7 ) and cytochrome c oxidase ( COX , EC 1 . 9 . 3 . 1 ) activities were similar between the two groups of calves but the COX : CS activity ratio was lower in the liver of the CO group . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In previous studies achieved in two K 562 DOX resistant sublines ( K562 / 0 . 2R and K562 / 0 . 5R ) , we have shown stable mitochondrial damage comparatively with sensitive parental cells , such as decrease of cytochrome c oxidase activity ( COX ; EC 1 . 9 . 3 . 1 ) and cytochrome aa 3 content . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Body weight and composition , 24 h energy metabolism ( whole body indirect calorimetry ) , and maximal activities of phosphofructokinase ( EC 2 . 7 . 1 . 11 ) , creatine kinase ( CK ; EC 2 . 7 . 3 . 2 ) , citrate synthase ( CS ; EC 4 . 1 . 3 . 7 ) , 3 hydroxyacyl CoA dehydrogenase ( HADH ; EC 1 . 1 . 1 . 35 ) , and cytochrome c oxidase ( COX ; EC 1 . 9 . 3 . 1 ) were determined from biopsy samples of the vastus lateralis taken before and after weight loss . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Three cDNA clones , whose greater expression was confirmed by Northern blot analysis , were identified as cytochrome oxidase ( COX ) subunits 1 , 2 , and 3 ( COX 1 , 2 , and 3 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The cDNA encodes a polypeptide of 604 amino acids that is 61 % identical to the previously isolated human Cox 1 polypeptide . ^^^ Both Cox 1 and Cox 2 mRNAs are expressed in HUVEC , vascular smooth muscle cells , monocytes , and fibroblasts . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The mRNA levels of ATPase beta , ATPase 6 , cytochrome oxidase ( COX ) VIb and COX 1 subunits were found to be 2 . 4 13 . 8 fold higher in brown adipose tissue ( BAT ) than in heart , skeletal muscle , brain and liver of mice . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The pal 4 nuclease ( termed 1 Sce 2 ) is encoded in the group 1 al 4 intron of the COX 1 gene of Saccharomyces cerevisiae . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Among the 5 complementation groups of mutants that affect the expression of COX 1 , 2 lack COX 1 transcripts , 1 produces incompletely processed COX 1 transcripts , and 2 contain normal levels of normal sized COX 1 transcripts . ^^^ The 3 complementation groups which affect the expression of both COX 1 and COB all have aberrant COX 1 and COB transcript patterns . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have studied the splicing pathway leading to the synthesis of cytochrome oxidase subunit 1 ( COX 1 ) mRNA , by analysing the transcription pattern of several oxi 3 splicing deficient mutants located in the first four introns of the gene . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Characterization of products derived from self splicing of intron aI 5 alpha which is located in the mitochondrial COX 1 gene of Saccharomyces cerevisiae . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
It is proposed that this region codes for the second exon of the cox 1 gene of Aspergillus mitochondrion . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Analyses of cytochrome absorption spectra and mitochondrial translation products of cells in which the suppressors are associated with various other mit mutations show that the suppressors restore cytochrome b and / or cytochrome oxidase ( cox 1 ) synthesis , as expected from their growth phenotype . ^^^ Interestingly enough when box 7 specific suppressors NAM 2 1 and mim 2 1 are associated with a complete cob box deletion ( leading to a total deficiency of cytochrome b and oxidase ) partial restoration of cox 1 synthesis is observed while cytochrome b is still totally absent . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
All M phi s exhibited COX 1 mRNA and protein ( i . e . , the constitutive isoform of COX ) , although elicited M phi s exhibited increased mRNA for COX 1 but decreased levels of protein , relative to resident M phi s . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 protein remained unaltered throughout . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The 5 ' and 3 ' termini of both the cytb and cox 1 gene are cryptic , the protein coding sequences being created by extensive insertion / deletion of Us in the corresponding mRNA sections . ^^^ Different patterns of editing have persisted in different lineages , however , since editing of cox 1 RNA and of relatively small 3 ' terminal RNA sections is not found in trypanosomatids . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A similar pattern was obtained previously for the mitochondrial encoded COX 1 and 2 mRNAs , but the latter accumulate at a 30 50 fold excess over the nuclear encoded COX subunit mRNAs during the cleavage stages . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS AND RESULTS : To investigate the effect of cardioplegia on mitochondrial calcium ( [ Ca2+ ] mt ) accumulation and the expression of cytochrome oxidase 1 ( COX 1 ) during global ischemia , mitochondria were isolated from mature ( age , 15 to 20 weeks ) and aged ( age > 130 weeks ) rabbit hearts after Langendorff perfusion . ^^^ COX 1 mRNA levels in aged hearts were lower in both control and global ischemia but were increased with cardioplegia . ^^^ Maximal velocities for COX 1 were significantly increased with Mg cardioplegia both in the mature and the aged myocardium . ^^^ CONCLUSIONS : K and / or Mg cardioplegia ameliorates [ Ca2+ ] mt accumulation in aged hearts during normothermic global ischemia and increases COX 1 mRNA levels to a level not significantly different from that found in mature hearts . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Both forms have been identified in the CNS , but only the distribution of COX 1 has been mapped in detail . ^^^ The distribution in the CNS was quite different from COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ A strong immunoreactivity for COX 1 was localized in the mucous neck cells of gastric gland . ^^^ A weak reactivity for COX 1 was also found in the mucous cell types in the cardiac gland and pyloric gland of the stomach as well as in the Brunner ' s gland of duodenum . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , the expression of COX 1 polypeptide was weak in both normal and cancerous specimens . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Nevertheless , COX 1 and COX 2 mRNAs and COX 2 protein were induced . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Immunoblots with a specific COX 1 antiserum revealed that COX 1 protein expression of MC was not affected by CSA . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Regardless of the conditions , cox 1 mRNA remained unchanged . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed and physiologically important . ^^^ PGI 2 synthesis can be augmented by virus mediated transfer COX 1 gene . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
ET 1 increased COX 2 , but not COX 1 , protein and mRNA levels . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Many protective processes are mediated through prostaglandins , whose synthesis is abolished by inhibition of the constitutive isoenzyme , cyclooxygenase 1 ( COX 1 ) or Prostaglandin H Synthase 1 ( PGHS 1 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ At both the protein and mRNA levels , the expression of COX 1 was constitutive and was not modulated by treatments with LPS , IL 10 , or IL 4 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Neither interleukin 1 beta nor the steroids affected numbers of COX 1 positive cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
There are two isozymes of prostaglandin endoperoxide ( PGH ) synthase ( cyclooxygenase ) called PGH synthase 1 and 2 or COX 1 and 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Immunological studies of human constitutive cyclooxygenase ( COX 1 ) using enzyme immunometric assay . ^^^ Polyclonal antisera and six distinct monoclonal antibodies ( mAbs ) were raised against constitutive cyclooxygenase ( COX 1 ) purified from ram seminal vesicles . ^^^ Different two site immunometric assays of ram COX 1 were established using different combinations of mAbs . ^^^ One combination ( solid phase CX 101 + CX 105 AChE ) exhibited the best sensitivity , with significant detection of concentrations as low as 23 pg / ml ( 0 . 3 fmol / ml of sheep COX 1 ) . ^^^ Unfortunately , this assay poorly cross reacted with human COX 1 from platelet extracts . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Freshly obtained AM contained lower levels of COX 1 than did fresh PM . ^^^ We conclude that , although both isoforms of COX are expressed in rat AM and PM , COX 1 is responsible for the majority of enzyme activity in both the basal and stimulated states . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Analysis of the COX 1 region previously reported to be altered in oncocytomas and the delta loop region of mtDNA showed no detectable abnormalities in the restriction pattern in 10 renal and five thyroid tumors . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Human Cox 1 and 2 polypeptides share 61 % primary sequence identity . ^^^ While the expression of Cox 1 is maximal in quiescent cells . ^^^ 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 P20674	Pubmed	SVM Score :0.0
These data suggest that the decrease in COX 1 and 3 subunits mRNA in affected brain regions may contribute to reduced brain oxidative metabolism in AD . . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ Human washed platelets were used as a source of COX 1 . ^^^ However , in contrast to these reference NSAIDs , CGP 28238 was at least 1000 fold less potent in inhibiting 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 P20674	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 . ^^^ In contrast , there was equivalent intensity of the COX 1 mRNA transcript between the normal mucosa and cancer in all 14 cases . ^^^ 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 P20674	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 . ^^^ In contrast , both COX 1 message and COX 1 protein levels were unaffected either by adrenalectomy or by dexamethasone administration . ^^^ 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 P20674	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 . ^^^ In contrast , minimal changes in cox 1 mRNA levels were observed after BDE or serum treatments . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ It has been generally accepted that physiologic renal production of prostaglandins is mediated by COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
It is now that there are two isozymes of prostaglandin endoperoxide ( PGH ) synthase ( cyclooxygenase ) called PGH synthase 1 and 2 or COX 1 and 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
There does not appear to be a protein bound COX 1 mRNA fraction . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The expression of the basal cyclooxygenase isoform ( COX 1 ) , which was constitutively expressed in proliferating mesangial cells , was not affected by IL 1 or CsA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
To further explore modulation of the Cox isoforms in RA synovial tissues , we examined the expression and modulation of Cox 1 and 2 in rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblast like cells ( synoviocytes ) . ^^^ Immunoprecipitation of in vitro labeled proteins and Western blot analysis demonstrated the presence of both Cox 1 and 2 under basal conditions in freshly explanted rheumatoid synovial tissues . ^^^ Cox 1 expression , under the same conditions , showed only minor variation . ^^^ 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 . ^^^ In sharp contrast , Cox 1 transcripts were not modulated by IL 1 beta or dex . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ A minor variation in 35S immunoprecipitated protein was obtained with the polyclonal anti Cox 1 antibody . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The reduction in cyclooxygenase activity paralleled the reduced mass of the constitutive form of cyclooxygenase ( COX 1 ) and PGI 2 synthase by approximately 80 % and 33 % , respectively . ^^^ Northern blot hybridization analyses of COX 1 mRNA steady state levels revealed no differences between normal and cholesterol enriched cells under basal conditions , indicating that cholesterol enrichment did not alter COX 1 gene expression . ^^^ Furthermore , cholesterol enrichment did not alter the relative levels of COX 1 mRNA expression over time following exposure of the cells to actinomycin D , indicating that cholesterol enrichment did not significantly alter the rate of COX 1 mRNA degradation . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We have previously discovered the new intron encoded endonuclease 1 Sce 3 by expressing , in E . coli , the ORF contained in the third intron of the yeast mitochondrial COX 1 gene . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The level of mRNA for cytochrome C oxidase ( COX ) subunit 1 ( COX 1 ) , which is encoded by mitochondrial ( mt ) DNA , progressively decreased in the hippocampal CA 1 neurons of gerbils from 3 h of reperfusion after 3 . 5 min of transient forebrain ischemia and completely disappeared at 7 days . ^^^ The activity of COX protein also showed an early decrease in CA 1 cells and was followed by reduction of the level of COX 1 DNA after 2 days . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ There is 95 % conservation of the nucleotide sequence in the open reading frame of COX 1 between the rat and the mouse , while the homology of the 3 ' untranslated region is 68 % except for a 150 bp segment adjacent to the stop codon which is nonhomologous with the mouse . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
TNF alpha increased the amounts of mRNA for COX 2 but not for COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , there was equivalent intensity of the COX 1 RNA transcript between the normal mucosa and tumor in all of the specimens examined . ^^^ 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 P20674	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 ) . ^^^ The activity of a number of NSAIDs has been investigated in several test systems , showing that most of those marketed have higher activities against COX 1 or are equipotent against both isoforms . ^^^ 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 P20674	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 . ^^^ COX 1 transcript , however , was undetectable irrespective of the presence of TGF alpha , duration of culture or the stage of follicular development . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , the level of COX 1 mRNA was unaffected by adjuvant injection . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ The 2 . 8 kb COX 1 message was detected in all lungs and seven hearts of eight control rats . ^^^ In lipopolysaccharide treated animals , COX 1 expression was reduced by approximately 5 fold in lungs and 2 fold in hearts as quantified by densitometry . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , it did not modify the protein concentration of COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 was detected in the endometrium during all five stages of the estrus cycle . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast to LPS , the PAF induced TX release is likely to depend on COX 1 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The results were compared with the inhibition of constitutive cyclooxygenase ( COX 1 ) in three parallel in vitro models : clotting guinea pig blood , human polymorphonuclear leukocytes , and purified COX 1 from ram seminal vesicles . ^^^ 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 P20674	Pubmed	SVM Score :0.0
In this study we measured the amounts of mRNA for a mitochondrial encoded subunit of cytochrome c oxidase ( COX 1 ) and for nuclear encoded actin during aerobic development , anaerobiosis , and aerobic acidosis ( artificial quiescence imposed by intracellular acidification under aerobic conditions ) . ^^^ The levels of both COX 1 and actin transcripts increased significantly during aerobic development . ^^^ COX 1 mRNA levels were tightly correlated with previous measures of COX catalytic activity , which suggests that COX synthesis could be regulated by message concentration during aerobic development . ^^^ Importantly , the levels of COX 1 and actin mRNA did not decline appreciably during the 6 h bouts of quiescence , even though protein synthesis is acutely arrested by these same treatments . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ This study aims to characterize the expression of the protein for COX 1 and 2 in the rat uterus and cervix during the estrous cycle , pregnancy , and labor , and in cultured myometrial cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
It was found that 13 out of 28 clones whose levels were altered were mitochondrial in origin including rRNA , COX 1 & 2 and the NADH Q reductase . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 message levels increased more slowly to two to threefold above control levels after 24 h incubation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
There is a constitutive enzyme COX 1 which has a wide tissue distribution . ^^^ The constitutive enzyme , COX 1 is responsible for the production of prostaglandins with multiple functions . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Tenidap inhibited calcium ionophore stimulated prostaglandin D 2 synthesis by rat basophilic leukemia cells ( COX 1 ) with an IC 50 of 20 nM . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The gastrointestinal and renal side effects of these drugs , in contrast , are thought to relate to their ability to inhibit the constitutive isozyme , COX 1 . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In this study , PGE 2 levels in lipopolysaccharide ( LPS ) challenged human whole blood and TxB 2 levels following blood coagulation were measured as biochemical index for cyclooxygenase ( Cox ) 2 and Cox 1 activity respectively . ^^^ Cox 1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS . ^^^ 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 P20674	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 P20674	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 . ^^^ Virus or non virus mediated transfer of COX 1 and eNOS are accompanied by augmented PGI 2 and NO synthesis , respectively . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ COX 1 was expressed constitutively in MEG 01 cells . ^^^ 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 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ A non significant effect was observed with COX 1 transcripts . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The structure of ovine COX 1 complexed with several NSAIDs has been determined . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 mRNA levels remained constant during the same period . ^^^ 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 contrast , COX 1 gene expression was constitutive in this cell line . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Gastric ulceration was not associated with a change in COX 1 mRNA and protein levels . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Western blot analysis demonstrated a significant COX 1 activity in unstimulated J 774 macrophages and in unstimulated human umbilical vein endothelial cells ( HUVEC ) . ^^^ 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 . ^^^ Therefore , in subsequent studies , the effect of mercaptoalkylguanidines on COX 1 activity was studied in HUVEC stimulated with arachidonic acid for 6 h , and in J 774 cells stimulated with arachidonic acid for 30 min . ^^^ In addition , the effect of mercaptoalkylguanidines on purified COX 1 and COX 2 activities was also studied . 3 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , COX 1 protein was unchanged in response to treatment with EGF . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The new paradigm is that COX 1 , a constitutive enzyme is thought to be a housekeeping protein , and to be important in generating prostaglandins necessary for physiological purposes , amongst which may be suppression of gastric acid secretion . ^^^ 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 P20674	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 . ^^^ Currently available non steroidal antiinflammatory drugs ( NSAIDs ) are widely used for the treatment of inflammatory diseases ; however , significant side effects due to inhibition of COX 1 limit their use . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The sparing of COX 1 activity in gastric mucosa gives rise to etodolac ' s noted gastric tolerance . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Expression of constitutive cyclo oxygenase ( COX 1 ) in rats with streptozotocin induced diabetes ; effects of treatment with evening primrose oil or an aldose reductase inhibitor on COX 1 mRNA levels . ^^^ The rate limiting enzyme in the control of prostanoid metabolism is constitutive cyclo oxygenase ( COX 1 ) . ^^^ This study examined the possibility that altered prostanoid metabolism derives from altered COX 1 expression in those tissues from diabetic rats , with characteristic changes in prostanoid production and related haemodynamics . ^^^ This account also describes a procedure for estimation of minute amounts of COX 1 mRNA by reverse transcription and competitive polymerase chain reaction ( RT cPCR ) amplification . ^^^ In streptozotocin diabetic rats ( STZ D , 55 mg / kg body weight ) , compared with age matched controls , the level of COX 1 mRNA ( in attomoles / micrograms tRNA + / 1SD ) was significantly decreased in sciatic nerve ( 0 . 50 + / 0 . 26 versus 0 . 89 + / 0 . 32 in controls ; P < 0 . 05 ) and thoracic aorta ( 3 . 99 + / 1 . 67 versus 8 . 80 + / 2 . 37 in controls ; P < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The cox 1 gene from Euglena gracilis : a protist mitochondrial gene without introns and genetic code modifications . ^^^ We present the nucleotide sequence of the cox 1 gene encoding subunit 1 of cytochrome c oxidase in Euglena gracilis , the first report on a mitochondrial gene from this protist . ^^^ The Euglena cox 1 gene does not exhibit any intron , and an amino acid alignment of Euglena COX 1 with homologous proteins shows that the universal genetic code is used . ^^^ Comparisons of the genomic and cDNA sequences of Euglena cox 1 indicate that the transcript does not undergo RNA editing as found in trypanosomes and in higher plants . ^^^ The phylogeny obtained with COX 1 protein sequences is in agreement with that obtained with nuclear rRNA sequences and places Euglena and Trypanosoma far apart from other eukaryotes . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , Cox 1 mRNA levels were not elevated in the carcinoma . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , there was no variation in immunoprecipitated Cox 1 protein or in activity . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Immunohistology showed expression of COX 1 in collecting duct cells , interstitial cells , endothelial cells , and smooth muscle cells of pre and postglomerular vessels . ^^^ In fetal kidney , COX 1 was primarily expressed in podocytes and collecting duct cells . ^^^ Expression levels of COX 1 in both cell types increased markedly from subcapsular to juxtamedullary cortex . ^^^ The expression of COX 1 in podocytes of the fetal kidney and its absence in adult glomeruli suggests that this isoform might be involved in glomerulogenesis . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Immunofluorescence for COX 1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress . ^^^ CONCLUSIONS : We concluded that anoxic stress increases COX 2 but not COX 1 levels in cerebral endothelium . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Two isoforms of COX have been characterized , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ Classic NSAIDs preferentially inhibit COX 1 in vitro , but it appears hazardous to judge their gastrointestinal ( GI ) safety profile from these data . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Two isoforms of COX have been characterized , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 large increase in selectivity of DFU over indomethacin was also observed in COX 1 mediated production of thromboxane B 2 ( TXB 2 ) by Ca2+ ionophore challenged human platelets ( IC 50 > 50 microM and 4 . 1 + / 1 . 7 nM , respectively ) . 3 . ^^^ Inhibition of purified recombinant human COX 1 by DFU was very weak and observed only at low concentrations of substrate ( IC 50 = 63 + / 5 microM at 0 . 1 microM arachidonic acid ) . ^^^ These data are consistent with a reversible competitive inhibition of COX 1 . 5 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Within vessels , the formation of nitric oxide ( NO ) or prostaglandins is normally catalysed in the endothelium by constitutive isoforms of NO synthase ( eNOS ) and cyclo oxygenase ( COX 1 ) , respectively . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 protein levels were not affected by arachidonic acid treatment either . ^^^ 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 . ^^^ This suggests that under these conditions , PGE 2 production is dependent on COX 1 . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in most tissues and its activity provides for the relative small amounts of PGs required for the mediation and modulation of normal physiological functions . ^^^ 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 . ^^^ This new class of NSAIDs will provide anti inflammatory and analgesic activity while circumventing the most serious side effects of the current available NSAIDs , resulting from their inhibition of the physiologically required COX 1 activity . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 is expressed constitutively and is known to be the site of action of aspirin and other nonsteroidal anti inflammatory drugs . ^^^ Treatment of the cells with PMA induced a time dependent increase in the expression of both COX 1 and COX 2 mRNAs . ^^^ The enzymatic activity of the PMA induced COX was measured in the presence of a panel of enzyme inhibitors , and the IC 50 values obtained were compared with those obtained for the inhibition of human platelet COX activity , a COX 1 selective assay . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Such inhibitors would preserve COX 1 , which is both constitutive and physiological , and thereby provide improved tolerability compared with currently used NSAIDs , which act upon both COX pathways . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ During the preimplantation period ( days 1 4 ) , the COX 1 gene was expressed in the uterine epithelium mainly on day 4 until the initiation of attachment reaction in the evening after which the expression was downregulated . ^^^ This COX 1 expression coincides with the generalized uterine edema required for luminal closure . ^^^ The COX 1 gene that was downregulated from the time of attachment reaction on day 4 was again expressed in the mesometrial and anti mesometrial secondary decidual beds on days 7 and 8 . ^^^ These results suggest that PGs generated by COX 1 are involved in decidualization and / or continued localized endometrial vascular permeability observed during this period . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 undergoes auto inactivation , which severely limits PGI 2 synthesis . ^^^ Overexpression of COX 1 in cultured endothelial cells by COX 1 gene transfer was accompanied by a higher capacity for and sustained synthesis of PGI 2 . ^^^ Adenovirus mediated COX 1 gene transfer to angioplasty damaged carotid arteries in pigs augmented PGI 2 synthesis and prevents thrombus formation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , no variation in the expression of COX 1 protein was observed . 5 . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Expression of mRNA for both COX 1 and 2 , but not for endothelial or inducible NOS , were significantly increased after long term endotoxin administration . ^^^ These prostaglandins were produced via COX 1 , which like COX 2 , is induced by endotoxin administration . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Two isoforms of COX exist , COX 1 , which is constitutively expressed , and COX 2 , which is an inducible isoform . ^^^ Prostaglandins synthesized by the constitutively expressed COX 1 are implicated in the maintenance of normal physiological function and have a ' cytoprotective ' action in the stomach . ^^^ 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 P20674	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 . ^^^ In volunteers , indomethacin 75 mg , but not meloxicam 7 . 5 mg , inhibited renal prostaglandin E 2 excretion and platelet aggregation ( COX 1 mediated effects ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ In contrast mRNA for COX 1 is detected equally often . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the enzyme responsible for prostanoid production , exists as two isoforms : constitutive COX 1 and inducible COX 2 . ^^^ We report that COX 1 behaves as a delayed response gene in PC 12 cells exposed to NGF . ^^^ Six hours following NGF treatment , COX 1 mRNA levels were elevated in PC 12 cells , reaching nearly 5 fold above basal levels at 12 h . ^^^ This increase was blocked by cycloheximide and was accompanied by concomitant increases in COX 1 protein and enzyme activity . ^^^ COX 1 protein remained elevated for at least 10 days and localized to the cytoplasm and neurites of NGF differentiated PC 12 cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 tissue expression : implications and predictions . ^^^ COX 1 displays the characteristics of a `` housekeeping ' ' gene and is constitutively expressed in almost all tissues . ^^^ COX 1 appears to be responsible for the production of prostaglandins ( PG ) that are important for homeostatic functions , such as maintaining the integrity of the gastric mucosa , mediating normal platelet function , and regulating renal blood flow . ^^^ 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 P20674	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 . ^^^ No changes were observed in COX 1 protein , localized in endothelial cell cytoplasm and the nuclear envelope . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In addition to constitutive COX 1 , inducible COX 2 has been discovered . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Both Cox 1 and 2 genes encode the two isoenzymes that carry out similar enzymatic steps . ^^^ 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 . ^^^ In contrast , Cox 1 overexpressing cells expressed high levels of the functional Cox 1 polypeptide in the endoplasmic reticulum and the nucleus . ^^^ Cox 1 overexpression also enhanced the tumor necrosis factor alpha induced apoptosis of ECV cells 2 fold . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In this case , inhibition of COX 1 by aspirin will also reduce the amount of precursors for vascular prostacyclin synthesis , provided , for example , from adhering platelets . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ No significant differences were observed in expression levels of COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This alteration in eicosanoid metabolism was associated with induction of cyclooxygenase ( Cox ) 2 and thromboxane synthase , but not Cox 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Reverse transcription PCR was performed with a preparation of total nucleic acids ( DNA+RNA ) , amplifying the sequences of interest ( targets ; mitochondrial transcripts : 12S rRNA , cytochrome c oxidase [ COX 1 ] mRNA ) together with an endogenous , non transcribed reference sequence ( template : D loop region of mtDNA ) . ^^^ The results revealed a ratio of 12S rRNA : mtDNA and COX 1 mRNA : mtDNA of 14 and 2 , respectively , or a ratio of 12 S rRNA : COX 1 mRNA of 7 in human left ventricle and are in good agreement with previously published values for rat liver and muscle . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
We observed higher abundances of mitochondrial encoded mRNAs ( COX 1 and ND 4 ) in cell lines established from adults than in fetal cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ To investigate whether rat COX 1 produces 8 epi PGF 2 alpha more efficiently than human COX 1 , we measured the ex vivo formation of 8 epi PGF 2 alpha and TXB 2 simultaneously in whole clotting blood . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Surprisingly , disruption of the COX 1 gene resulted in generally healthy mice . ^^^ The results obtained to date with the COX 1 deficient mice indicate that some of the physiological roles previously attributed to COX 1 may not be entirely correct . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Within vessels , cyclooxygenase ( COX ) is expressed constitutively ( COX 1 ) in endothelial cells where its production of prostacyclin is thought to contribute to the maintenance of vascular integrity . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Therefore , the purpose of this study was to determine the effect of dexamethasone on estrous cycle length and COX 1 and 2 production by the uterine endometrium of cyclic cattle . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Total renal COX 1 mRNA decreased 50 % following the LS diet and did not change after the HS diet . ^^^ COX 1 and 2 mRNAs were unevenly distributed along the cortical medullary axis with ratios of the cortex : outer medulla : papilla of 1 : 3 : 23 and 1 : 1 : 2 , respectively . ^^^ Conversely , in medullary zones , COX 1 mRNA correlated directly with salt intake . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury . ^^^ Down regulation of COX 1 may result in decreased synthesis of cytoprotective eicosanoids and additionally exacerbate liver injury . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , COX 1 did not change with obstruction . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In the present report , we describe a sensitive assay for the inhibition of human COX 1 based on the production of prostaglandin E 2 by microsomes from U 937 cells incubated with a subsaturating concentration of arachidonic acid . ^^^ 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 . ^^^ A good correlation was obtained between the IC 50 values for the inhibition of microsomal COX 1 and both the inhibition of TXB 2 production by Ca2+ ionophore challenged platelets and the inhibition of prostaglandin E 2 production by CHO cells stably expressing human COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In two patients with AISA we identified point mutations of mtDNA affecting the same transmembrane helix within subunit 1 of cytochrome c oxidase ( COX 1 ; ie , complex 4 of the respiratory chain ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 like immunoreactivity was observed in most cell types with strongest staining in macrophages . ^^^ In placenta , COX 1 and 2 expression was unchanged after pre eclampsia . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Immunocytochemistry of sections of normal rat spinal cord with specific COX 1 antiserum revealed little specific COX 1 like immunoreactivity in the grey matter . ^^^ With the same antiserum , intense COX 1 like immunoreactivity was observed in the cytoplasm , nuclear membrane and axonal processes of small to medium sized ( < 1000 microns 2 ) dorsal root ganglion ( DRG ) cell bodies . 5 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cox 1 expression was differentially enhanced in the PHT superior mesenteric artery and thoracic aorta during the development and progression of PHT . ^^^ These data suggest that PHT is associated with enhanced Cox 1 expression within the splanchnic vasculature concomitant with elevated plasma prostacyclin levels and a significant pressor response to indomethacin in PHT animals . ^^^ We conclude that enhanced Cox 1 expression results in increased prostacyclin levels that partially contribute to the maintenance of the hyperemia typical of PHT . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Activation of rat fibroblastic 3Y1 cells with interleukin 1 beta ( IL 1 beta ) and tumor necrosis factor alpha ( TNF alpha ) induced delayed prostaglandin ( PG ) E 2 generation over 6 48 h , which occurred in parallel with de novo induction of type IIA secretory phospholipase A 2 ( sPLA 2 ) and cyclooxygenase ( COX ) 2 , without accompanied by changes in the constitutive expression of type 4 cytosolic PLA 2 ( cPLA 2 ) and COX 1 . ^^^ 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 P20674	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 . ^^^ COX 1 staining was almost exclusively localized in synovial lining cells , with no significant differences in the MOD between the diseases . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The cells expressed transcripts and protein for cyclooxygenase ( COX ) 1 and 2 enzymes , and their release of prostaglandin E 2 ( PGE 2 ) was inhibited by selective COX 1 and 2 inhibitors . ^^^ Adult human colonic subepithelial myofibroblasts may influence epithelial cell function via products of COX 1 and 2 enzymes , such as PGE 2 and secreted ECM proteins . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , COX 1 mRNA and protein levels were unaltered by TNF alpha treatment as determined by RT PCR and immunoblot analysis , respectively . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Polyclonal antibodies to human COX 1 and COX 2 were localized with immunoperoxidase staining . ^^^ COX 1 was localized exclusively to the prelaminar and lamina cribrosa regions of the optic nerve head . ^^^ No staining for COX 1 was observed in the nerve fiber layer or the myelinated optic nerve . ^^^ COX 1 was associated with the astrocytes of the glial columns and the cribriform plates , but not with the endothelia lining the capillaries . ^^^ In glaucoma , more astrocytes appeared to be stained with antibody to COX 1 than in normals and staining was intensely perinuclear . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 expression was clearly observed in uterine artery . ^^^ Immunohistochemical localization of COX 1 was endothelium > VSM , with both cell types showing an increase in COX 1 during the third trimester of pregnancy . ^^^ COX 1 protein and messenger RNA ( mRNA ) levels were also detectable in collagenase dispersed endothelial cells , with expression of COX 1 in uterine artery endothelial cells dramatically increased during the third trimester of pregnancy at both the level of protein ( 346 . 4 + / 28 % of nonpregnant controls , P < 0 . 0005 ) and mRNA ( 51 . 04 + / 7 . 98 fold of nonpregnant controls , P < 0 . 001 ) . ^^^ We conclude that the pregnancy induced increases in prostacyclin production by uterine arteries is largely due to a dramatic increase in expression of COX 1 mRNA and associated protein predominantly occurring in the uterine artery endothelium and , to a lesser extent , in the VSM . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer and that the inhibition of colon carcinogenesis is mediated through modulation of prostaglandin production by cyclooxygenase ( COX ) isozymes ( COX 1 and 2 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ COX 1 mRNA abundance rose progressively from fetal to NB 1 to NB 2 , increasing 12 fold overall . ^^^ In parallel , immunoblot analysis revealed a progressive increase in COX 1 protein , rising fourfold from fetal lambs to NB 2 . ^^^ Immunohistochemistry for COX 1 showed intense immunostaining in endothelial cells at all ages . ^^^ COX 1 was also expressed in airway epithelium at all ages , with a greater number of epithelial cells staining positively in NB 2 compared with fetal and NB 1 groups . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Control tissues ( liver , spleen , and kidney ) showed the expected predominance of COX 1 gene expression . ^^^ 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 P20674	Pubmed	SVM Score :0.0
PGE 2 production by COX 1 from exogenous AA in non stimulated cells was also inhibited by M 5011 with a potency less than that of ketoprofen . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The ontogenetic increase in mRNA levels for a mitochondrial encoded subunit of cytochrome c oxidase ( COX 1 ) and for nuclear encoded actin is blocked by anoxia and aerobic acidosis ( artificial quiescence imposed by intracellular acidification under aerobic conditions ) . ^^^ Further , the levels of COX 1 and actin mRNA do not decline appreciably during 6 h bouts of quiescence , even though protein synthesis is acutely arrested across this same period . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Ribonuclease protection assay demonstrated minimal COX 1 mRNA expression in glomeruli of control rat kidneys and a gradual increase of expression from day 1 to day 10 after administration of monoclonal anti rat Thy 1 antibody . ^^^ Expression of cPLA 2 mRNA , which was undetectable in normal glomeruli , was induced on day 1 and increased gradually in a pattern similar to that of COX 1 mRNA expression . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , specific COX 1 inhibition was not effective . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ RESULTS : Expression of COX 1 protein was substantially higher in 30 of 44 tumor samples than in any of the 14 normal tissue specimens . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The level of COX 1 mRNA remained stable through all stages of acute gastric damage . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
As expected , they lack mtDNA encoded subunits COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 constitutive isoform of COX , COX 1 , has clear physiological functions . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 in constitutively expressed . ^^^ Conventional NSAIDs also inhibit the synthesis of cytoprotective prostaglandins by COX 1 in the gastrointestinal tract . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
IL 1 beta induced COX 2 but not COX 1 protein . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 has clear physiologic functions . ^^^ 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 P20674	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 P20674	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 . ^^^ Using enzyme kinetics , we found that COX 1 ( Ki = 143 microM ) and Ca 1 cPLA 2 ( Ki = 121 microM ) were competitively inhibited by ciprofibrate , but the inhibition was not physiologically significant . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively produced and is believed to be involved in regulating normal cellular processes , such as gastrointestinal ( GI ) cytoprotection , vascular homeostasis , and renal function . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Protective PGs , which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney , are synthesized by COX 1 . ^^^ 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 P20674	Pubmed	SVM Score :0.0
This study investigates the activity of cytochrome oxidase ( COX ) , the terminal enzyme in the mitochondrial electron transport chain , and the expression of two mitochondrial DNA genes related to COX ( mRNA of subunit 1 of COX [ COX 1 ] and the RNA component of the 12S ribosomal subunit [ 12S rRNA ] ) , in quadriceps femoris muscle biopsies obtained from COPD patients with various degrees of arterial hypoxemia , and from healthy sedentary control subjects of similar age . ^^^ The measurements of mRNA COX 1 and 12S rRNA were normalized to the mRNA of actin , which is a housekeeping gene not influenced by hypoxia . ^^^ The COX 1 mRNA content was not different between patients and control subjects but patients with chronic respiratory failure had higher levels of 12S rRNA ( p < 0 . 05 ) , which were again inversely related to PaO 2 ( Rho 0 . 49 , p < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 results demonstrate that the potentiation of opioid inhibition of GABAergic synaptic transmission in PAG is largely a result of inhibition of COX 1 activity . ^^^ 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 P20674	Pubmed	SVM Score :0.0
By immunocytochemistry , COX 1 and COX 2 enzymes were localized to NSCLC tumors . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Treatment of endothelial cells with aspirin or a COX 1 antisense oligonucleotide inhibits COX 1 activity / expression and suppresses tube formation . ^^^ 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 P20674	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 P20674	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 P20674	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 . ^^^ In conclusion the induction of COX 1 by VEGF is not involved in the mitogenic response of endothelial cells , but may be an important regulatory mechanism in the maintenance of vascular integrity . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 levels remained stable with all treatments . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
However , it did not affect the expression of mRNA or protein for cyclo oxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 mRNA levels were approximately the same in groups fed diets containing either level of menhaden oil , but were increased by approximately 30 % in the LFS and HFS groups ( P < 0 . 05 ) . ^^^ These results demonstrate that dietary n 6 PUFAs upregulate COX 2 and , to some extent , COX 1 expression . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Immunoperoxidase studies on kidney biopsies showed COX 1 staining in glomerular arterioles and other renal vessels , with no evident difference between lupus biopsies and control specimens taken from either individuals who were free of renal disease or patients with non lupus nephropathies . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
BACKGROUND & AIMS : Selective inhibitors of cyclooxygenase ( COX ) 2 are being developed as gastrointestinal sparing anti inflammatory drugs based on the premise that this isoform is solely responsible for prostaglandin synthesis at sites of inflammation , whereas COX 1 produces prostaglandins important for maintenance of mucosal integrity . ^^^ 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 . ^^^ RESULTS : Significant anti inflammatory effects were only observed at doses of the drugs that inhibited COX 1 . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 , though present , appears not to participate significantly in stimulus induced PGE 2 production in P388D1 macrophages . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In the peritoneal cells , the mRNA expression for the constitutive cyclooxygenase 1 ( COX 1 ) was unchanged by PQ administration . ^^^ PGs involved in the induction of writhing thus seem to be derived from a COX 1 reaction . ^^^ Oral administration of mofezolac , a non steroidal anti inflammatory drug which potently inhibits COX 1 , suppressed the PQ induced writhing and peritoneal accumulation of PGs without affecting mRNA expression for both COX isoforms in mice . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ RESULTS : COX 1 protein was expressed at equal levels in normal , Crohn ' s disease , and ulcerative colitis colonic epithelial cells . ^^^ Immunohistochemistry of normal , Crohn ' s colitis , and ulcerative colitis tissue showed equivalent COX 1 expression in epithelial cells in the lower half of the colonic crypts . ^^^ CONCLUSIONS : COX 1 was localized in the crypt epithelium of the normal ileum and colon , and its expression was unchanged in IBD . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : In the human whole blood assay , the ratio of IC 50 values for COX 1 vs . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Insects capable of flight at 30 days of age were found to have a 4 fold higher abundance of cox 1 mitochondrial encoded RNA compared to flightless insects . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ The area of gastric lesions was determined by planimetry , gastric blood flow ( GBF ) was measured by the H 2 gas clearance technique , mucosal PGE 2 generation was measured by radioimmunoassay , and expression of COX 1 and COX 1 mRNA was determined by reverse transcription polymerase chain reaction ( RT PCR ) , quantitative RT PCR with [ 32P ] dCTP and immunohistochemistry . ^^^ The expression of COX 1 mRNA , as determined by RT PCR , quantitative RT PCR and immunohistochemistry was found in intact gastric mucosa and after LPS administration . ^^^ 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 P20674	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 . ^^^ COX 1 was increased by TGFbeta 1 , but only in astrocytes . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ In contrast , COX 1 protein and mRNA were hardly detected in any of the AM preparations . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The decrease in protein synthesis was associated with a 30 50 % reduction in the levels of most individually radiolabeled translation products including the COX subunits and specifically , a 23 % decrease in COX 1 protein steady state levels according to Western analysis . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Caco 2 cells expressed very low levels of Cox 1 but highly expressed Cox 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Histocytochemical , immunocytochemical , and cellular functional imaging studies of these clones showed the cells within the clones were heterogeneous with respect to cytochrome c oxidase ( COX ) function , COX 1 content , and mitochondrial respiratory chain activity . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cyclooxygenation is a key enzymatic step in the synthesis of prostanoids . 1990 2 isoforms of the enzyme cyclooxygenase have been identified : Prostanoids synthesized by the constitutive cyclooxygenase ( COX 1 ) are involved in physiological homeostasis . ^^^ 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 P20674	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 . ^^^ CONCLUSIONS : CDB is an effective anti inflammatory / analgesic agent whose mechanism of action appears to be associated with inhibition of COX 1 activity . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
They inhibit both COX 1 and COX 2 with up to 33 fold selectivity for COX 2 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Induction of cyclooxygenase ( COX ) 2 but not COX 1 gene expression in apoptotic cell death . ^^^ By 6 h after hippocampal colchicine injection in rat , COX 2 ( but not COX 1 ) mRNA expression was elevated . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 mRNA expression was not affected by ulceration . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
To dissect the contributions of the two cyclooxygenase ( COX ) isoforms to the synthesis of PGs during pregnancy , we have characterized the parturition phenotype of COX 1 deficient mice . ^^^ We find that mice with targeted disruption of the COX 1 gene have delayed parturition resulting in neonatal death . ^^^ Results of matings of COX 1 deficient females with COX 1 intact males , and blastocyst transfer of COX 1 deficient or intact embryos into wild type foster mothers , proved necessity and sufficiency of maternal COX 1 for the normal onset of labor . ^^^ COX 1 expression is induced in gravid murine uterus and by in situ hybridization ; this induction is localized to the decidua . ^^^ Measurement of uterine PGs further confirmed that COX 1 accounted for the majority of PGF2alpha production . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 was expressed in the crypt epithelium and lamina propria mononuclear cells ; DSS treatment down regulated COX 1 expression only in the epithelium . ^^^ Dimethyl PGE 2 reversed the effect of DSS on COX 1 expression . ^^^ Recovery was associated with a return to normal COX 1 expression in the epithelium . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Two isoforms of cyclooxygenase ( COX ) have been described : constitutive ( COX 1 ) and inducible ( COX 2 ) . ^^^ In contrast , there were no significant changes in COX 1 mRNA expression . ^^^ 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 ) . ^^^ No change of COX 1 expression was seen . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Because the writhing terminated within 30 min after PQ injection , the prostaglandins involved in the induction of writhing seem to be derived from COX 1 . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The expression of COX 1 mRNA , measured by Northern blot analysis , was similar in virgin , lactating , pregnant , and post lactational animals of the same age . ^^^ Ovariectomized animals exhibited significantly lower levels of COX 1 mRNA ( approximately 40 % ) compared to the sham operated controls or the ovariectomized animals treated with estradiol and progesterone . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 is expressed at high levels in the collecting ducts and renal vasculature of all species and in a small number of papillary interstitial cells in rats , monkeys , and humans . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Oxidative stress and aging reduce COX 1 RNA and cytochrome oxidase activity in Drosophila . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The findings suggest that TX is largely Cox 1 derived . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Besides a number of nucleotide variants , a single novel missense mutation , which may contribute to the disease phenotype , was found in the mitochondrial encoded COX 1 gene ( G6480A ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
BACKGROUND : There are two isoforms of cyclo oxygenase ( COX ) , namely COX 1 and COX 2 . ^^^ COX 1 is constitutively expressed in most tissues and in blood platelets . ^^^ The metabolites derived from COX 1 are probably involved in cellular housekeeping functions . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 is constitutive and makes PGs that protect the stomach and kidney from damage . ^^^ For instance , COX 2 ( and not COX 1 ) is thought to be involved in ovulation and in labor . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ This is particularly likely in large blood vessels , where , under physiological conditions , the release of prostacyclin by COX 1 , present in the endothelium , is an important component of cardiovascular homeostasis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
An increase of COX 1 expression was detected at 12 hours of shear loading by Western blotting . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Incubations of NNK with COX 1 and 2 produced both activation and detoxification products by alpha carbon hydroxylation and N oxydation pathways , respectively . ^^^ Bioactivation of NNK was more extensive by COX 2 than COX 1 . ^^^ Anti COX 1 and 2 , arachidonic acid , ASA , and NS 398 inhibited NNK bioactivation by COX 1 and 2 from 22 49 % . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ The inhibition of COX 1 in the intact cell system was IC 50 = 0 . 5 microM , that of indomethacin 0 . 0038 microM . ^^^ 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 P20674	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 . ^^^ In contrast , JTE 522 did not inhibit human COX 1 prepared from human platelets at concentrations up to 100 microM . ^^^ On the other hand , JTE 522 was less potent at inhibiting calcium ionophore induced thromboxane B 2 production in washed human platelets ( COX 1 ) ( IC 50 value = 6210 nM ) . ^^^ In contrast , the inhibitory activity of JTE 522 on human COX 1 was not affected by preincubation time . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In addition , COX 1 messenger RNA ( mRNA ) abundance was greater in newborn than in fetal PAEC , and this was not due to a difference in COX 1 mRNA stability . ^^^ Thus , the developmental upregulation of PGI 2 synthesis is conserved in early passage PAEC and pulmonary VSM , and is related to a maturational increase in COX 1 gene expression . ^^^ Further studies with the cultured cell model will enable determination of the factors that directly regulate COX 1 expression in the developing pulmonary vasculature . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
This order of potency : indomethacin > piroxicam > L 745 , 337 > > DFU suggests the involvement of the COX 1 isozyme in the mediation of the secretory response to LBK . 4 . ^^^ 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 . ^^^ The expression of COX 1 mRNA was reduced by LBK by 44 % . 7 . ^^^ Immunohistochemical studies demonstrated the presence of COX 1 immunoreactivity in the basal cells of the intact rat epididymis . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 mRNA levels did not change with stretch . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Spinal levels of COX 1 were not altered at any time point of the peripheral inflammation . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ COX 1 mRNA and protein were constitutively expressed in uninfected , control Ad5LacZ or Ad5IkappaB infected HT 29 cells with no apparent change following TNF alpha exposure . ^^^ 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 P20674	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 P20674	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 . ^^^ These cells expressed COX 1 at rest and both COX isoforms on treatment with phorbol 12 myristate 13 acetate . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We have studied by reverse transcriptase polymerase chain reaction ( RT PCR ) and Western blot the expression of COX 1 and 2 mRNA and protein in resting and activated peripheral blood or Jurkat T cells . ^^^ Both peripheral blood and Jurkat T cells expressed COX 1 and 2 mRNA and protein . ^^^ COX 1 was constitutively expressed and did not change after OKT 3 stimulation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In this study we have demonstrated the presence of two immunoreactive isoforms of cyclooxygenase ( COX 1 and 2 ) , and the modulating effects of n 3 fatty acids on their expression , in N nitrosomethylurea ( NMU ) induced rat mammary tumors . ^^^ 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 P20674	Pubmed	SVM Score :0.0
They expressed mRNA and protein for COX 1 and 2 enzymes and their release of prostaglandin E 2 was inhibited by selective COX 1 and 2 inhibitors . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The aim of this study was to determine the contributions of COX 1 and 2 to the production of specific prostanoids by unstimulated and stimulated intestinal epithelial cells . ^^^ 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 . ^^^ Unstimulated prostanoid formation was not decreased by the COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 levels were similar between paired tissues . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ An enhanced expression of COX 1 was not observed in well differentiated HCCs . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A distinctly underexpressed PCR product of the CNF kidneys showed over 98 % identity with a mitochondrially encoded cytochrome c oxidase ( COX 1 ) . ^^^ Using a full length COX 1 cDNA probe , we verified down regulation of COX 1 mRNA to 1 / 4 of normal kidney values on Northern blots . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ On the other hand , IFN gamma had no effect on expression of COX 1 and 2 mRNA . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Cox 1 was constitutively expressed at all stages of pregnancy examined , but it did exhibit localized up regulation in the trophoblast and necks of uterine glands at early implantation sites . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The COX 1 isoform , however , is a constitutive enzyme with homeostatic functions . ^^^ 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 P20674	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 . ^^^ COX 1 mRNA expression was low in human amnion and chorion decidua and did not change with gestational age . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
The predominant isozyme expressed in cortical thymic epithelial cells was COX 1 , while COX 2 predominated in the medulla . ^^^ In contrast , IFN gamma down regulated COX 1 activity , but not expression , in cortical cells . ^^^ 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 P20674	Pubmed	SVM Score :0.0
In this study we used immunohistochemistry and quantitative autoradiographic methods to study the expression pattern of two cytochrome oxidase subunit proteins ( nuclear encoded COX 4 and mitochondrial encoded COX 1 ) in the hippocampus in relation to the development of AD type pathology . ^^^ Levels of COX 4 but not of COX 1 were related to the amount of hyperphosphorylated tau accumulated in the same hippocampal region but not to the amount of amyloid deposited in sporadic AD . ^^^ In Down ' s syndrome COX 1 and COX 4 were similarly increased in the presence of AD pathology in non tangle bearing neurones . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Celecoxib displays classic competitive kinetics on COX 1 ( Ki=10 16 microM ) . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is detectable in most tissues on a constant level and is responsible for the synthesis of prostaglandins with cytoprotective effects . ^^^ 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 P20674	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 P20674	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 . ^^^ The data showed that the wild type , COX 1+ / , and COX 1 / mice all responded to LPS with a 1 degrees C rise in Tc within 1 h ; the fever gradually abated over the next 4 h . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : The following are representative examples of inhibitors with different distinct selectivity for COX 1 / 2 . ^^^ Indomethacin as a COX 1 selective compound inhibited PGHS 1 ( IC 50 : 0 . 002 microM ) 200 times stronger than PGHS 2 ( IC 50 : 0 . 43 microM ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
From this analysis , we found that cyclooxygenase 1 ( COX 1 ) , 5 lipoxygenase ( 5 LOX ) , and FLAP were universally expressed in all cancer cell lines tested . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 , which is constitutively expressed in many tissues ( including the gastrointestinal tract , platelets , and kidney ) is responsible for producing prostanoids that regulate normal housekeeping or physiologic functions . ^^^ 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 P20674	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 P20674	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 . ^^^ In healthy brain , COX 1 was expressed in single macrophages / microglial cells . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is expressed physiologically while inducible COX 2 is expressed in pathological situations . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Time course studies using specific inhibitors of COX 1 show that AA stimulates PKC activity and PKC then stimulates PGE 2 production . ^^^
Interacting proteins: P00395 and P20674	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 both normal and transformed cells constitutive COX 1 was evident and in gallbladder cancer cells lysophosphatidyl choline ( LPC ) induced the formation of constitutive COX 1 enzyme . ^^^ 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 P20674	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 ) . ^^^ METHODS : COX 1 inhibition was determined by measuring thromboxane B 2 ( TXB 2 ) generation from clotting whole blood ex vivo after single oral doses of 7 . 5 and 15 mg meloxicam and 75 mg diclofenac and at steady state ( 15 mg meloxicam daily and 150 mg diclofenac daily ) . ^^^ Because of the increase in EC 50 at steady state , COX 1 is relatively spared when the lower dose of 7 . 5 mg is administered . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ During the menstrual cycle , the highest expression of COX 1 occurred in luteal phase endometrium and was localized to the surface and glandular epithelium . ^^^ The stromal cells did not express detectable levels of COX 1 at any time . ^^^ 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 . ^^^ With the onset of pregnancy , COX 1 expression in epithelial cells decreased dramatically . ^^^
Interacting proteins: P00395 and P20674	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 ( + / + ) . ^^^ Exogenous gonadotropin stimulation with PMSG and hCG produced a comparable 4 fold increase in ovarian PGE 2 levels in wild type and COX 1 ( / ) mice . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In this study , we found no evidence to support a role for COX 1 or 2 in the 20 : 4 , n 6 inhibition of hepatocyte lipogenic gene expression . ^^^ 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 . ^^^ Despite the absence of COX 1 and 2 expression in primary hepatocytes , prostaglandins ( PGE 2 and PGF2alpha ) suppressed fatty acid synthase , l pyruvate kinase , and the S 14 protein mRNA , while having no effect on acyl CoA oxidase or CYP4A2 mRNA . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed , whereas COX 2 is induced by proinflammatory stimuli . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 was only mildly upregulated in AD brain . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The beneficial actions of nonsteroid anti inflammatory drugs ( NSAID ) can be associated with inhibition of cyclo oxygenase ( COX ) 2 whereas their harmful side effects are associated with inhibition of COX 1 . ^^^ 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 . ^^^ In conclusion , this full in vitro analysis of COX 1 / 2 selectivities in human tissues clearly supports the theory that inhibition of COX 1 underlies the gastrointestinal toxicity of NSAIDs in man . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ RESULTS : COX mRNA was detected in unstimulated cells , but stimulation with IL 1 for up 12 h did not modify the levels of COX 1 mRNA . ^^^ However , it did not inhibit COX 1 activity . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 2 selective drugs are desirable not only because they spare COX 1 and so avoid gastrointestinal toxicity , but also because COX 2 selective agents are only weakly acidic and therefore avoid substantial accumulation in the gastric mucosa . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 , the predominantly constitutive form of the enzyme , is expressed throughout the body and provides certain homeostatic functions , such as maintaining normal gastric mucosa , influencing renal blood flow , and aiding in blood clotting by abetting platelet aggregation . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The production of thromboxane B 2 in whole blood allowed to clot at 37 degrees C for 60 min was assessed as an index of platelet COX 1 activity . ^^^ 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 P20674	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 . ^^^ RESULTS : The majority of all types of untreated cultured cells expressed COX 1 ( 75 % of HASM , 75 % of MRC 5 fibroblasts and 72 % of NHBE cells ) . ^^^ IL 1beta ( 24 h incubation ) or BK ( 4 h incubation ) had no effect on COX 1 expression in any of the cells studied . ^^^ 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 P20674	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 P20674	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 . ^^^ No differences in COX 1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Increasing amounts of experimental and clinical data support the role of selective cyclooxygenase ( COX ) 2 inhibition in anti inflammatory processes and the role of COX 1 inhibition in increasing the frequency of side effects . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The cyclooxygenase isoenzymes ( COX 1 and 2 ) catalyze the rate limiting steps in prostanoid biosynthesis . ^^^ COX 1 and 2 genes encode two isoenzymes with overlapping yet distinct expression patterns and functions . ^^^ Physiologically , various extracellular stimuli such as growth factors , cytokines and tumor promoters regulate the expression of COX 1 and 2 genes at both transcriptional and post transcriptional levels . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ A 4 day old brain expressed lower levels of bNOS ( 5 fold ) , ecNOS ( 10 fold ) , and COX 1 ( 2 fold ) than the 6 week old pig . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 levels did not vary . ^^^ COX 1 was unaffected . ^^^ We conclude that in inner medulla , COX 2 but not COX 1 is upregulated by hyperosmolality . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Using wild type and COX 1 ( / ) mice , we examined the role of COX 1 derived PGs on day 4 of pregnancy , when its expression is maximal . ^^^ Vascular permeability and PG concentrations were reduced in COX 1 ( / ) mice , but by less than the expected amount . ^^^ After ovariectomy , uterine vascular permeability declined in both groups , but returned to baseline in wild type and was exaggerated in COX 1 ( / ) females after treatment with ovarian steroids . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in synovia , particularly in synovial lining cells . ^^^ There are no significant differences in immunostaining of COX 1 in vivo in inflammatory compared with non inflammatory arthritis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Molecular modeling of arachidonic acid in sheep COX 1 confirms that this L shaped conformation is possible , with the carboxylate moiety binding to Arg 120 and the omega end positioned above Ser 530 in a region termed the top channel . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Since all NSAIDs inhibit COX 1 , they all cause upper GI mucosal damage . ^^^ What is needed are specific COX 2 inhibitors that do not inhibit COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We identified four known genes specifically expressed by 1 , 25D3 / DEX treated ST 2 stromal cells : 1 ) a family of rat organic anion transporters , 2 ) Na / K ATPase ss subunit , 3 ) tazarotene induced gene 2 ( TIG 2 ) , and 4 ) prostaglandin G / H synthase 1 , or cyclooxygenase 1 ( Cox 1 ) . ^^^ Northern blot analysis of treated and untreated ST 2 cell total RNA using either a DRD derived Cox 1 cDNA or a Cox 1 specific oligonucleotide confirmed the steroid regulation of Cox 1 mRNA . ^^^ The response of osteoclast supporting ST 2 cells to 1 , 25D3 / DEX treatment may be one prostaglandin mediated event which specifically involves Cox 1 regulation . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Sequence analysis of the mitochondrial encoded COX subunit genes identified a heteroplasmic G > A transition at nucleotide position 6930 in the gene for subunit 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ MATERIALS AND METHODS : COX 1 inhibition in intact cells was assessed employing two systems : measurement of aggregation in human washed platelets and assessment of TXB 2 formation in HEL cells . ^^^ 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 . ^^^ RESULTS : In intact human cells , lornoxicam showed a balanced inhibition of COX 1 / 2 exhibiting the lowest IC 50 ( 0 . 005 microM / 0 . 008 microM ) of the large panel of NSAIDs tested . ^^^ Similar results were obtained in the whole blood for COX 1 / 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA expressions were determined by Northern blot assays with mouse specific cDNA probes . ^^^ In comparison , COX 1 mRNA expression was not affected by either LPS stimulation or EPA incubation . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cotransfection of sPLA 2 5 with cyclooxygenase ( COX ) 2 , but not with COX 1 , into human embryonic kidney 293 cells dramatically increased the interleukin 1 dependent PGE 2 generation occurring over a 24 h of culture period . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 was detected in the collecting ducts , thin loops of Henle and portions of the renal vasculature . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ No significant changes of COX 1 RNA or protein expression were observed either with gestational age or labour . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Expression of COX 1 and 2 mRNA and protein was studied by Northern blot analysis and Western blot analysis , respectively . ^^^ 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 . ^^^ There was no difference in expression of COX 1 mRNA between unstimulated cells and IL la 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 P20674	Pubmed	SVM Score :0.0
In contrast , CMT 3 and 8 do not inhibit COX 1 expression in A 549 human epithelial cells at the level of protein and mRNA accumulation or modification of COX 1 protein . ^^^ CMT 3 and 8 inhibit the sp . act . of COX 2 ( but not COX 1 ) in cell free extracts . ^^^ These results demonstrate differential action of CMT 3 ( Metastat ) on COX 1 and 2 expression , which is distinct from other tetracyclines . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Compared with control brains , accumulation of COX 1 was detected in 20 50 % of all cells in both low and high grade gliomas . ^^^ Double labeling experiments revealed COX 1 expression in subsets of macrophages / microglial cells within the tumor parenchyma and in areas of infiltrative tumor growth . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 mRNA levels were low in time controls , and ischemic stress had no significant effect on COX 1 expression . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , SC 58560 , a COX 1 selective inhibitor , was 100 fold less potent for inducing MIC death than its structural congener SC 58236 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Steady state levels of the mtDNA encoded subunit COX 1 showed a mild reduction , but spectrophotometric analysis revealed a dramatic decrease in COX 1 associated heme a 3 levels . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ COX 1 mRNA expression was absent or below the level of detection via in situ hybridization . ^^^ COX 1 immunohistochemistry demonstrated uniform faint cytoplasmic staining in tumour cells and stromal inflammatory cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 mRNA level did not differ between the normal and ulcerated tissues . ^^^ In contrast , COX 1 , EGF , and TGF beta 1 mRNA expression was not affected by IL 1RA . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
This study examines the expression and regulation of the prostaglandin synthesizing enzymes cyclooxygenase 1 ( COX 1 ) and 2 in the CCD . ^^^ By indirect immunofluorescence using isoform specific antibodies , COX 1 and 2 immunoreactivity was localized to all cell types of the murine M 1 CCD cell line . ^^^ 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 drugs did not affect COX 1 protein expression . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Reduced mitochondrial heme aa 3 with both treatments was accompanied by approximately 50 % reduced , mitochondrial genome encoded COX 1 and 2 mRNAs and nuclear genome encoded COX Vb mRNAs , but no change in COX 4 mRNA level . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
A diverse polymorphism was observed with most of the probes used , i . e . the cob , cox 1 , atp 6 , rrn 18 , rrn 26 and atp 9 regions , whereas , no polymorphic band was observed with a probe for the coxII region . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ We report that COX 1 message and immunoreactivity are localized to human hippocampal CA 3 and CA 4 neurons , granular neurons in neocortical layer 4 , and occasional cortical pyramidal neurons . ^^^ Quantitative in situ hybridization showed no differences between COX 1 mRNA levels in control and AD CA 3 hippocampal neurons . ^^^ COX 1 immunoreactivity was also present in microglial cells in gray and white matter in all brain regions examined . ^^^ COX 1 appeared to be expressed in microglial cells regardless of their activation state as determined by HLA DR immunostaining . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The presence of the COX 1 inhibitor valerylsalicylate ( 500 microM ) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal NaCl concentration ( 5 + / 1 . 8 nGU / min at high NaCl , and 30 . 5 + / 9 . 4 nGU / min at low NaCl ; P < 0 . 01 , n = 8 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ High dose flosulide induced a decrease in glomerular prostanoid production possibly because of COX 1 inhibition . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
OBJECT : Recently , two different cyclooxygenase ( COX ) genes , COX 1 and 2 , were identified . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Furthermore , we compared the expression patterns of the nuclear encoded COX5c and COX5b genes with the expression pattern of the mitochondrial encoded COX 1 gene among several organs by Northern blot analysis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
RT PCR assays revealed a 1 . 5 ( p < 0 . 001 ) to 4 fold ( p < 0 . 001 ) increased expression of COX 1 mRNA in the MS infused brain samples . ^^^ The data further show that the MS induced prostanoid responses appear to be mediated via COX 1 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The constitutive isoform , COX 1 , was unchanged . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Celecoxib is primarily an inhibitor of cyclooxygenase ( COX ) 2 and , at therapeutic concentrations in humans , does not inhibit the COX 1 isoenzyme . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In Western blot analyses , positive bands of liver type PGF synthase and constitutive COX 1 were observed at positions approximately 37 kDa and 70 72 kDa , respectively . ^^^ COX 1 was present on the membranes of the nucleus and endoplasmic reticulum of the endothelial cells and Kupffer cells . ^^^ Double immunostaining for PGF synthase and COX 1 showed that both enzymes were present in the same endothelial cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ Cox 1 inhibition resulted in effects on proliferation , differentiation , and matrix production typical of 24R , 25 ( OH ) ( 2 ) D ( 3 ) . ^^^ In contrast , inhibition of Cox 2 had no effect , indicating that 24R , 25 ( OH ) ( 2 ) D ( 3 ) exerts its effects via Cox 1 . ^^^ Inhibition of Cox 1 also blocked 24R , 25 ( OH ) ( 2 ) D ( 3 ) dependent increases in PKC . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Thus , it is assumed that the gastroduodenal ulcerogenic and functional responses to hypothermic stress are modified by cNOS / NO as well as COX 1 / PGs . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ By contrast , gastrointestinal lesions were not observed , and platelet COX 1 activity was unaffected , at anti angiogenic doses of SC 236 ( 1 6 mg / kg / day ) . ^^^ Furthermore , a COX 1 selective inhibitor , SC 560 , was ineffective at doses up to 10 mg / kg , a dose that completely blocked platelet COX 1 activity in these mice . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ No spontaneous gastrointestinal inflammation was detected in mice homozygous for either mutation , despite almost undetectable basal intestinal PGE ( 2 ) production in COX 1 ( / ) mice . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ It reduces cancer cell proliferation , induces cancer cell apoptosis , and spares COX 1 induced cytoprotection of the gastrointestinal tract . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 mRNA and protein were expressed in the wound exudate , the skin surrounding the wound and in normal skin . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ All tissues were subjected to immunohistochemical staining for COX 1 , 2 , and TUNEL method for apoptosis detection , and the following results were obtained . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Endothelial and vascular smooth muscle ( VSM ) COX 1 protein levels and uterine artery endothelial cell COX 1 mRNA levels were compared . ^^^ Using immunohistochemistry and Western analysis , the primary location of COX 1 protein was the endothelium ; that is , we observed 2 . 2 fold higher COX 1 protein levels in intact versus endothelium denuded uterine artery and a 6 . 1 fold higher expression in the endothelium versus VSM ( P < 0 . 05 ) . ^^^ COX 1 protein levels were observed to be higher ( 1 . 5 fold those of LUT ) in uterine artery endothelium from FOL versus either OVEX or LUT nonpregnant ewes ( P < 0 . 05 ) , with substantially higher COX 1 levels seen in pregnancy ( 4 . 8 fold those of LUT ) . ^^^ Increases in uterine artery endothelial COX 1 protein were highly correlated to increases in the level of COX 1 mRNA ( r ( 2 ) = 0 . 66 ; P < 0 . 01 ) for all treatment groups ( n = 6 8 per group ) , suggesting that increased COX 1 protein levels are regulated at the level of increased COX 1 mRNA . ^^^ No change in COX 1 expression was observed between groups in a systemic ( omental ) artery . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The COX 1 selective inhibitor , SC 560 , had no effect upon prostaglandin synthesis in its COX 1 specific concentration range , but did significantly reduce prostaglandin synthesis at higher , non selective concentrations . ^^^ CONCLUSIONS : Fetal membranes contain both COX 1 and COX 2 at term , but only COX 2 contributes towards prostaglandin synthesis . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Why acetylated COX 1 does not synthesize 15 ( R ) hete . ^^^ 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 . ^^^ Because the COX isoforms are structurally similar and share approximately 60 % amino acid identity , we postulated that differences within the cyclooxygenase active sites must account for the inability of acetylated COX 1 to make 11 and 15 HETE . ^^^ Residues Val 434 , Arg 513 , and Val 523 were predicted by comparison of the COX 1 and 2 crystal structures to account for spatial and flexibility differences observed between the COX isoforms . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
BACKGROUND : Non steroidal anti inflammatory drugs ( NSAIDs ) inhibit cyclo oxygenase ( COX ) , which leads to suppression of COX 1 mediated production of gastrointestinal protective prostaglandins . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Expression of COX 1 and 2 protein and mRNA were examined with immunostaining and reverse transcription polymerase chain reaction , respectively . ^^^ 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 P20674	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 P20674	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 . ^^^ Both the Cox 1 mRNA , quantified in the whole lung homogenate , and the cellular localization of Cox 1 were unchanged in response to LPS . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Our data show that the cytosolic Group 4 PLA ( 2 ) and COX 1 are expressed in all of them , whereas the secretory forms of PLA ( 2 ) , ( Groups IIA , and 5 ) , have a more restricted expression . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is broadly distributed in normal , as well as in neoplastic , tissues . ^^^ In a rat model of angiogenesis , we observe that corneal blood vessel formation is suppressed by celecoxib , but not by a COX 1 inhibitor . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Nonsteroidal anti inflammatory drugs ( NSAIDs ) like aspirin and indomethacin that block COX 1 and 2 have been shown to have beneficial effects for tumor patients . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Cox 1 immunolabelling was almost exclusively restricted to small diameter DRG neurons ( < 1000 microm 2 ) , and was extensively colocalized with calcitonin gene related peptide ( CGRP ) and isolectin B 4 ( IB 4 ) . ^^^ Cox 1 was present in 65 % and 70 % of CGRP and IB 4 labelled neurons , respectively . ^^^ Cox 1 labelling was also found in neurons expressing the sensory neuron specific ( SNS ) Na+ channel . ^^^ 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 . ^^^ In primary tissue culture , cox 1 immunolabelling persisted in vitro for up to 9 days and was present in morphologically identical neurons . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
HN 56249 inhibited platelet aggregation as a measure of COX 1 activity only moderately ( IC 50 26 . 5+ / 1 . 7 microM ) . ^^^ COX 1 was only weakly inhibited ( IC 50 867+ / 181 microM ) . ^^^ 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 P20674	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 P20674	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 P20674	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 . ^^^ COX 1 expression remained unchanged . ^^^ 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 P20674	Pubmed	SVM Score :0.0
In contrast , two selective COX 1 inhibitors , valeryl salicylate and ketorolac , had no significant inhibitory effect on PDGF stimulated DNA synthesis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Expression of iNOS or COX 1 was not changed after CPB . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the rate limiting enzyme for prostaglandin synthesis , exists in two isoforms , COX 1 and COX 2 . ^^^ The rat COX 1 gene expresses an alternatively spliced mRNA COX 1 splice variant ( SV ) that may , at best , code for a truncated COX 1 protein . ^^^ COX 1 mRNA was significantly reduced in the aged , and COX 1SV mRNA was significantly higher in the adults compared with the young and aged stomach . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Also , COX 1 was expressed in the neoplastic cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Compared to healthy controls , significant ( P=0 . 0006 ) accumulation of COX 1 expressing macrophages / microglial cells was detected in Drck ' s granulomas . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 mRNA and protein were detected in the intact mucosa . ^^^ COX 1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 protein was unchanged . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Platelet COX 1 inhibition by chronic administration of low dose aspirin before LPS did not alter the symptomatic and febrile responses to LPS , but the increment in urinary PGI M and Tx M were both partially depressed . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In basal conditions , at 3 and 11 weeks of age COX 1 was expressed in the kidneys of all rats more markedly in medulla than in cortex . ^^^ After salt loading , the expression of COX 1 was enhanced in the medulla and that of COX 2 reduced in the cortex . ^^^ LH rats differed from controls by a significantly more marked increase in medullary COX 1 expression . ^^^ The present work excludes any primary generalized increase in the renal expression of the genes that control the synthesis of vasoconstrictor prostanoids in LH rats , but suggests that medullary COX 1 is upregulated by salt in these animals . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 expression , on the other hand , has been referred to as constitutive or non inducible . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
However , both COX 1 and 2 are expressed by cells of the ductus arteriosus . ^^^ 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 P20674	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 . ^^^ COX 1 leads , for example , to the production of prostaglandins that are cytoprotective for the gastric mucosa . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
These human fibroblasts constitutively expressed cytosolic PLA ( 2 ) ( cPLA ( 2 ) ) and COX 1 enzymes , and exhibited delayed PGE ( 2 ) generation in response to IL 1beta . ^^^ 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 P20674	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 . ^^^ The COX 1 selective inhibitor SC 560 also attenuated uterine and ovarian PG production after LPS but did not inhibit PTL as efficiently as SC 236 . ^^^ COX 1 deficient mice , which show delay in the onset of term labor , exhibited no delay in onset of PTL after LPS . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Unstimulated rat GEC in culture primarily express COX 1 . ^^^ When stimulated with sublytic C5b 9 , COX 2 was significantly up regulated , whereas COX 1 was not affected . ^^^ The results in cultured GEC were extended to GEC injury in vivo by examining COX 1 and 2 expression in PHN . ^^^ Glomeruli from rats with PHN expressed significantly more COX 1 and COX 2 , as compared with normal rats . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : COX 1 / 2 gene expression was examined in the thyroid epithelial cell line Nthy ori 3 1 using semi quantitative RT PCR and Western blot analysis . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Here , we report COX 1 expression following focal cerebral infarctions ( FCI ) . ^^^ In healthy control brains , COX 1 was localized by immunohistochemistry to a few endothelial cells , single neurons and rare , evenly distributed brain microglia / macrophages . ^^^ Double labeling experiments confirmed co expression of COX 1 by CD68+ microglia / macrophages . ^^^ Thus , COX 1 appeared to be expressed in microglial cells regardless of their activation state . ^^^ However , the prolonged accumulation of COX 1+ microglia / macrophages restricted to peri infarctional areas enduring the acute post ischemic inflammatory response points to a role of COX 1 in tissue remodeling or in the pathophysiology of secondary injury . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Increased supply of arachidonic acid by explosive activation of cytosolic phospholipase A ( 2 ) allowed mPGES to be coupled with COX 1 . mPGES colocalized with both COX isozymes in the perinuclear envelope . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Employing a human gall bladder cancer cell line , mitogenesis , apoptosis and prostaglandin E ( 2 ) ( PGE ( 2 ) ) formation were evaluated in response to serum and hepatocyte growth factor and transforming growth factor alpha stimulation in the presence and absence of specific COX 1 and 2 inhibitors . ^^^ 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 P20674	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 . ^^^ COX 1 expression was detected in smooth muscle cells in both benign and malignant bladders . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 ( + ) lamina propria cells nearly doubled in number during inflammation ; expressed a T lymphocyte marker ; but retained an unchanged quantity of immunoreactive COX 1 protein per cell . ^^^ The number of newly appeared COX 2 ( + ) lymphocytes remained < 50 % that of COX 1 ( + ) cells . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ As a result , drugs that have little or no COX 1 activity across their therapeutic dosage range have been developed . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and 2 protein expression in corneal epithelium was determined by Western blot . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ No treatment group showed significant inhibition of COX 1 as assessed by thromboxane B 2 generation in clotting whole blood . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ We have studied the kinetics of PGE 2 and TXA 2 synthesis under conditions that rely on COX 1 or 2 activity . ^^^ This pattern was observed irrespective of whether PGH 2 was produced by COX 1 or COX 2 or whether it was added directly . ^^^ These properties provide an alternative explanation to notional linkage or compartmentalization of COX 1 or 2 with the respective terminal synthases and that therapeutically induced changes in eicosanoid ratios toward predominance of TXA 2 may have unwanted effects in long term anti inflammatory and anti arthritic therapy . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Immunoreactive COX 1 also was very weak in all cases of benign tissues . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Our results show that COX 1 in the uterine epithelium is the major source of PGs during labor and that COX 1 ( / ) females experience parturition failure that is reversible by exogenous PGs . ^^^ Using embryo transfer experiments , we also show that successful delivery occurs in COX 1 ( / ) recipient mothers carrying wild type pups , establishing the sufficiency of fetal PGs for parturition . ^^^ 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 P20674	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 P20674	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 . ^^^ Thus , functional coupling between COX 1 and cPGES / p23 may contribute to production of the PGE ( 2 ) that plays a role in maintenance of tissue homeostasis . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Cox 1 staining showed a massive transient increase in diseased glomeruli at day 6 , localized mainly to mesangial cells coinciding with cell proliferation , which also peaked at day 6 . ^^^ Upregulation of Cox 1 was also evident at the mRNA level ( 4 fold ) . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We observed that NNK induces COX 1 expression and activates the nuclear factor kappaB ( NF kappaB ) , in U 937 cells . ^^^ These data suggest that ROS , generated during pulmonary metabolism of NNK could act as signal transduction messengers and activate NF kappaB , which will subsequently induce COX 1 activity and increase PGE ( 2 ) synthesis . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The loss of COX 1 expression after castration correlates with the specific loss of anion secretion induced by bradykinin and possibly other hormones . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ CONCLUSIONS : Both COX 1 and 2 are expressed and contribute to the increase in PGI ( 2 ) in patients with atherosclerosis , whereas TXA ( 2 ) is generated by COX 1 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Treatment of the mice with the selective COX 1 inhibitor , piroxicam , attenuated the hypophagic responses to IL 1 and LPS . ^^^ 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 P20674	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 P20674	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 . ^^^ Spotblots of nonstimulated iris extracts showed positive staining for COX 1 immunoreactivity ( ir ) only . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Recurrent myoglobinuria due to a nonsense mutation in the COX 1 gene of mitochondrial DNA . ^^^ RESULTS : The authors identified a nonsense mutation ( G5920A ) in the COX 1 gene in muscle mtDNA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
BACKGROUND & AIMS : Selective cyclooxygenase ( COX ) 2 inhibitors produce less gastric damage than conventional nonsteroidal anti inflammatory drugs ( NSAIDs ) , suggesting that NSAIDs cause damage by inhibiting COX 1 . ^^^ We tested this hypothesis in rats by using a selective COX 1 inhibitor ( SC 560 ) . ^^^ Selectivity of the drugs for COX 1 vs . ^^^ A COX 1 preferential inhibitor , ketorolac , was also evaluated . ^^^ RESULTS : SC 560 markedly reduced gastric prostaglandin synthesis and platelet COX 1 activity , but spared COX 2 and did not cause gastric damage . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
BACKGROUND : It is suggested that the gastrointestinal toxicity of conventional non steroid anti inflammatory drugs ( NSAIDs ) is due to a ' topical ' effect in addition to inhibition of the mucosal constitutive cyclo oxygenase 1 ( COX 1 ) enzyme . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cox 1 mRNA was expressed in the liver , kidney and lung , but not in the heart . ^^^ 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 P20674	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 . ^^^ In this study we describe the immunohistochemical localization of Cox 1 and 2 in the human male fetal and adult reproductive tracts . ^^^ There was no Cox 1 expression in fetal samples ( prostate , seminal vesicles , or ejaculatory ducts ) , and only minimal expression in adult tissues . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A faint band of Cox 1 mRNA was observed in the livers of both normal and transgenic mice . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Colon tumors were analyzed for iNOS , COX 1 , and COX 2 expression and enzymatic activities . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Finally , Western blot analysis showed enhanced expression of COX 1 and 2 in the two arteries with ageing . 5 . ^^^ These results suggest that the decrease in acetylcholine induced relaxation with ageing involves reduced NO mediated dilatation and increased generation of vasoconstrictor prostanoids most likely from COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 is a constitutively produced isoenzyme that is involved in the synthesis of eicosanoids that have important homeostatic functions , for example , in the gastric mucosa and platelets . ^^^ 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 P20674	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 P20674	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 . ^^^ However , experimental evidence suggests that both , the analgetic and anti inflammatory action of COX inhibitors , might also require inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Increasing amounts of experimental and clinical data support the role of selective cyclooxygenase ( COX ) 2 inhibition in anti inflammatory processes and the involvement of COX 1 inhibition in the side effects associated with non steroidal anti inflammatory drug use . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The expression of cyclooxygenase ( COX ) 2 and IL 1beta mRNA ( messenger ribonucleic acid ) was enhanced by mechanical tension as determined by use of reverse transcription polymerase chain reaction ( RT PCR ) , whereas COX 1 and IL 1beta converting enzyme mRNA remained unchanged . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
METHODS AND RESULTS : Using washed platelets from normal donors and tyrphostin A 47 and aspirin as tyrosine kinase and COX 1 inhibitors , respectively , we found that tyrphostin A 47 downregulated ( 1 ) the thrombin activated conformational change of alpha ( IIb ) beta ( 3 ) , ( 2 ) actin polymerization and cytoskeletal reorganization , and ( 3 ) the quantity of tyrosine phospho rylated proteins associated with the reorganized cytoskeleton . ^^^ Therefore , tyrosine phosphorylation is a major component of early signaling events and of COX 1 independent mechanisms of thrombin induced platelet reactivity . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 ) . ^^^ Treatment with COX 1 selective concentrations of flurbiprofen did not affect cell growth in any of the three tumor cell lines . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The results obtained support the notion that PG involved in regulating renal hemodynamic and excretory function when NO synthesis is reduced are mainly dependent on COX 1 activity . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Immunohistochemistry was used to assess the expression of COX 1 and 2 , and 13 samples were also assessed using immunoblotting ( six BPH and seven cancers ) . ^^^ RESULTS : For both BPH and prostate cancer , COX 1 expression was primarily in the fibromuscular stroma , with variable weak cytoplasmic expression in glandular / neoplastic epithelial cells . ^^^ 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 P20674	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 P20674	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 . ^^^ Western blot analysis confirmed COX 1 and 2 expression . ^^^ COX 1 and COX 2 immunostaining was increased in Helicobacter pylori gastritis , particularly the mid glandular zone and lamina propria inflammatory cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ For renal hemodynamics the given evidence point to COX 1 as the predominant enzyme , but further investigations are required . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Other genes , including c fos , c myc , thymidine kinase , proliferating cell nuclear antigen , BRCA 1 , BRCA 2 , and Cox 1 , were not significantly affected by TF 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , strong COX 1 expression was frequently localised to Kupffer cells , endothelial cells , and occasionally to hepatocytes , but not to bile duct epithelial cells . ^^^ In approximately half of moderately and poorly differentiated but not well differentiated cholangiocarcinomas , weak to moderate COX 1 staining was found in tumour cells while COX 1 expression in Kupffer cells was much more pronounced . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 immunoreactivity was predominantly observed in macrophages / microglial cells . ^^^ The number of COX 1 expressing macrophages / microglial cells was significantly lower in primary oligodendrogliomas than in primary anaplastic oligodendrogliomas ( P < 0 . 0001 ) and in anaplastic oligodendroglioma relapses ( P=0 . 011 ) . ^^^ Patients with low COX 1 labeling scores in the primary tumors had significantly longer time to progression and overall survival ( P=0 . 0285 ) than those with high COX 1 labeling scores . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Expression of cyclooxygenase 1 ( COX 1 ) in labial salivary glands of Sjgren ' s syndrome . ^^^ Labial salivary gland tissue samples were analysed immunohistochemically using anti COX 1 and COX 2 antibodies . ^^^ All biopsy samples from 15 patients with SS were stained for COX 1 . ^^^ In contrast , COX 1 immunostaining was not detected in normal salivary gland tissues . ^^^ Co expression of COX 1 and CD 68 was confirmed by mirror section technique and double antibody immunostaining . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Northern blot analysis and reverse transcription polymerase chain reaction ( RT PCR ) , using complementary DNA probes and primers designed from the human COX sequences , were used to determine COX 1 and 2 ( cyclooxygenase isoforms 1 and 2 ) messenger RNA ( mRNA ) expression . ^^^ 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 . ^^^ Sequencing revealed that this PCR product was 90 % homologous to a portion of the human COX 1 gene ( Genbank M 59979 ) . ^^^ CONCLUSIONS AND CLINICAL RELEVANCE : Detection of COX 1 by RT PCR of RNA obtained from canine platelets is a novel finding . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS : The authors studied COX 1 and 2 expression in 20 tumors of the lung , colon , and breast ( 60 total ) by using commercially available monoclonal and polyclonal antibodies on formalin fixed , paraffin embedded tissue . ^^^ COX 1 immunoreactivity was essentially weak to moderate in all tissues evaluated . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The cellular localization of COX 1 and COX 2 were determined by immunohistochemistry and double immunofluorescence . ^^^ RESULTS : In control specimens , COX 1 was detected in stromal cells in the lamina propria . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed as a ' housekeeping ' enzyme in most tissues . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
This characteristic has prompted us to suggest that its administration , at levels equivalent to those found in human plasma following therapeutic doses , slightly inhibits cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX has two isoforms : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We also find that the NSAIDs , which reduce prostaglandin synthesis by inhibiting COX 1 and 2 enzymes , might also be expected to lower APP levels . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Time course of COX 1 inhibition was determined ex vivo by measurement of serum thromboxane B 2 ( TXB 2 ) concentrations . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In addition , there is evidence that COX 1 displays pro inflammatory properties , depending on the organ and on the stage of the inflammatory response . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
These results suggest that NO increases HCO 3 secretion in Bullfrog duodenum in vitro , and this action is dependent on cGMP related COX 1 activation and mediated by PGs . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS : Fresh human monocytes were stimulated with arachidonic acid ( AA ; 10 microM ) for 15 min and prostaglandin E 2 ( PGE 2 ) and thromboxane B 2 ( TXB 2 ) production were used as a measure of COX 1 activity . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX is expressed in two isoforms , constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Acting as an agonist of endothelial B 2 kinin receptors Bk rises [ Ca2+ ] 1 with a subsequent activation of constitutive COX 1 and NOS 3 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A significant and selective decrease of cyclooxygenase ( COX ) 2 activity was observed in the colon of rats receiving GTE ( 23 + / 3 vs . 117 + / 30 mU / mg protein in controls ) , whereas COX 1 showed no alterations . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In general , most NSAIDs inhibit COX 1 and 2 by similar mechanisms . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 mRNA levels did not change during the periovulatory interval , and COX 1 immunostaining of granulosa cells was not detected . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 primary cortical neurons , both indomethacin ( COX 1 / 2 nonselective inhibitor ) and aspirin ( COX 1 preferential inhibitor ) reduced basal and kainic acid induced PGE ( 2 ) production significantly and prevented neuronal cell death after kainic acid treatment . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
All tumor cell lines examined , regardless of phenotype , express both cox 1 and cox 2 proteins in vitro . ^^^ Cox 1 is detected in both metastatic and nonmetastatic tumors . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ In contrast , a COX 1 inhibitor given systemically , but not spinally , reduced carrageenan evoked thermal hyperalgesia but had no effect by any route with spinal SP hyperalgesia . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ On the other hand , COX 1 and iNOS were not detected in either normal or KA treated spinal cords . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ COX 1 is constitutively expressed , and is responsible for the synthesis of PGs necessary for gastroprotection and normal renal function . ^^^ 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 . ^^^ COX 1 immunoreactivity was weak to mild throughout each tissue evaluated and did not change in the neoplastic or stromal cells of the polyps . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Two isoforms of the enzyme cyclooxygenase have been identified : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In survivors , Mphi COX 1 peaked at > 100 times baseline in both right BAL and left BAL by 60 minutes ( before resuscitation ) . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX has recently been shown to have at least two isoforms , termed COX 1 and COX 2 . ^^^ The life threatening gastrointestinal side effects of NSAID are caused by their inhibition of COX 1 , which results in increased gastrointestinal bleeding and decreased ability to induce platelet aggregation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , the key enzyme for synthesis of prostaglandins , exists in two isoforms ( COX 1 and COX 2 ) . ^^^ COX 1 is constitutively expressed in the gastrointestinal tract in large quantities and has been suggested to maintain mucosal integrity through continuous generation of prostaglandins . ^^^ 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 P20674	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 ) . ^^^ The results from COX1ko mice suggest that COX 1 is not necessary for the decreased milk intake following IL 1 and LPS . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The inhibitory effect of indomethacin , but not celecoxib or NS 398 , on ectopic activity may suggest that a tonic generation of PGI ( 2 ) by COX 1 could contribute to neuropathic pain . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 mRNA expression did not change with age in cortex or medulla . ^^^ Lipopolysaccharide treatment did not alter COX 1 mRNA expression in infantile or adult rats . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Cox 1 catalyzes the synthesis of thromboxane A 2 ( Tx A 2 ) , which causes platelet activation , vasoconstriction , and smooth muscle proliferation . ^^^ 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 P20674	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 P20674	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 P20674	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 . ^^^ The binding energies and structures were compared with pharmacological parameters and available results with COX 1 . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Administration of 6 mg / kg LPS to rats i . p . resulted 6 h later in induction of NOS 2 and the membrane associated PGE synthase ( mPGES ) expression , and decreased constitutive COX ( COX 1 ) expression . ^^^ The LPS induced increase in PGE ( 2 ) concentration was mediated by NOS 2 derived NO dependent activation of COX 1 pathway and by induction of mPGES . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Curcumin markedly inhibited the mRNA and protein expression of COX 2 , but not COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The expression of constitutive enzymes , ecNOS and COX 1 , followed the opposite pattern . ^^^ COX 1 was significantly reduced in advanced gastric tumors ( P=0 . 007 ) and tumors larger than 5 cm ( P=0 . 007 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ RESULTS : Stomach , small bowel , and large bowel tissue COX 1 mRNA levels in the newborn were significantly lower ( P < 0 . 01 ) than in the adult . ^^^ 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 P20674	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 . ^^^ COX 1 inhibition would represent a major mechanism for cutaneous adverse reactions to NSAIDs . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The expression of COX 1 is not or only poorly regulated , the prostaglandins produced by it are responsible for the protection of the gastric mucosa , maintenance of normal kidney function and platelet aggregation . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS : Expression of COX 1 and 2 was assessed by confocal laser microscopy , immunohistochemistry , Western blot analysis , and real time RT PCR in human eyes with different forms of glaucoma ( primary open angle , angle closure , congenital juvenile , and steroid induced ) , as well as in age matched control eyes . ^^^ RESULTS : In normal eyes , ocular COX 1 and 2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body . ^^^ 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 P20674	Pubmed	SVM Score :0.0
RA alone [ 10 mg / ( kg . d ) for 5 d ] increased plasma and liver PG concentrations by increasing COX 1 protein expression ( twofold that of control rats ) . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 and COX 1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Thus , in normal rat gastric mucosa specific inhibition of COX 1 does not elicit mucosal lesions despite near maximal suppression of gastric prostaglandin formation . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Likewise , the selective COX 1 inhibitor SC 560 also did not cause gastric damage , despite causing a significant decrease in PGE ( 2 ) contents . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Protein expression of COX 1 and NF kappaB was not affected by daunorubicin . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Using mRNA and immunoglobulin probes , specific for prostanoid receptors and for prostaglandin endoperoxide synthase ( COX 1 and 2 ) , we sought to define , by in situ and in vitro techniques , changes in PGE 2 receptors and synthesis in cell populations of precancerous familial adenomatous polyposis ( FAP ) colonic mucosa . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Protein levels of mitochondrial transcription factor A ( Tfam ) and nuclear and mitochondrial encoded subunits of respiratory chain complex 4 ( COX 1 and COX 4 ) as well as citrate synthase activity were analysed in muscle biopsy samples of vastus lateralis in six healthy male subjects before and after 4 weeks of one legged cycle training . ^^^ Tfam , COX 1 and COX 4 levels all increased with training , with no differences observed between the legs . ^^^ The increases of COX 1 and COX 4 indicate a concurrent increase of nuclear and mitochondrial encoded subunits of respiratory enzyme complex 4 at the protein level in skeletal muscle in response to increased muscle activity . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The LPS ( 100 microg / kg , i . v . ) induced hyperalgesia was completely abolished by pretreatment with the microinjection of diclofenac ( an inhibitor of COX 1 and 2 ) at 1 . 0 ng into the bilateral POA . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In vivo and in vitro studies suggest that NO aspirin ( acetylsalicylic acid ) exerts more potent antithrombotic action than aspirin , probably by coupling the ability to inhibit COX 1 with the anti adhesive effect of NO . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Thromboxane A 2 ( TxA 2 ) , which is primarily synthesized by platelet COX 1 , causes irreversible platelet aggregation , vasoconstriction and smooth muscle proliferation , all of which are linked to coronary heart disease ( CHD ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ In contrast , many prenylated flavonoids , such as kuraridin , kuwanon C and sophoraisoflavanone A , inhibited COX 1 activity . ^^^ Of the COX 1 inhibiting prenylated flavonoids , kuraridin , kurarinone , and sophoraflavanone G , all having a C 8 lavandulyl moiety , showed potent activity ( ic ( 50 ) = 0 . 1 to 1 microM ) comparable to that of indomethacin ( ic ( 50 ) = 0 . 7 microM ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Both nonsteroidal anti inflammatory drugs , such as ibuprofen , and the prototypical selective cyclooxygenase ( Cox ) 2 inhibitors DuP 697 and NS 398 block the inhibition of Cox 1 by aspirin in vitro . ^^^ Here , we have evaluated the relative potential of ibuprofen and various coxibs to interfere with the inactivation of Cox 1 by aspirin by using purified enzyme and calcium ionophore activated human platelets . ^^^ The irreversible inactivation of Cox 1 by aspirin can be antagonized by ibuprofen and coxibs , albeit with widely different potencies . ^^^ The rank order of potencies for this process ( ibuprofen > celecoxib > valdecoxib > rofecoxib > etoricoxib ) parallels that obtained for the inhibition of Cox 1 mediated thromboxane B ( 2 ) production by calcium ionophore stimulated platelets . ^^^ The EC ( 50 ) value for the antagonism against 10 microM aspirin for each drug is approximately 10 to 40 fold lower than the corresponding IC ( 50 ) value for inhibition of platelet Cox 1 activity , consistent with the much weaker initial binding of aspirin to Cox 1 as compared with arachidonic acid . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 2 and COX 1 proteins were determined by Western blot analysis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Despite the utility of cyclooxygenase ( COX ) inhibition as an antiinflammatory strategy , prostaglandin ( PG ) products of COX 1 and 2 provide important regulatory functions in some pathophysiological states . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Deficiency of COX 1 causes natriuresis and enhanced sensitivity to ACE inhibition . ^^^ Conventional non steroidal anti inflammatory drugs ( NSAIDs ) , which inhibit both COX isoforms ( COX 1 and 2 ) , cause sodium retention , exacerbate hypertension , and interfere with the efficacy of certain anti hypertensive agents such as angiotensin converting enzyme ( ACE ) inhibitors . ^^^ METHODS : To address this question , we studied mice with targeted disruption of the COX 1 ( Ptgs 1 ) gene . ^^^ To study interactions with the renin angiotensin system , ACE inhibitors were administered and mice with combined deficiency of COX 1 and the angiotensin 2 subtype 1A ( AT1A ) receptor were generated . ^^^ RESULTS : On a regular diet , BP in COX 1 / mice was near normal . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Immunostaining for COX 1 , COX 2 , and PGD 2 synthase was unchanged . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Up regulation of COX 1 in chronic venous leg ulcers could produce prostacyclin , which contributes to angiogenesis . ^^^ Thus , inhibition of COX 1 by non steroidal anti inflammatory drugs ( NSAIDs ) could increase the local ischaemia and hypoxia associated with chronic venous ulcers . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Lineweaver Burk plot analysis indicated that gamma mangostin competitively inhibited the activities of both COX 1 and 2 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In particular , it was suggested that maintenance of gastric mucosal integrity relies exclusively on COX 1 . ^^^ Recently , it was shown that a selective COX 1 inhibitor does not damage the mucosa in the healthy rat stomach , although mucosal prostaglandin formation is near maximally suppressed . ^^^ However , concurrent treatment with a COX 1 and a COX 2 inhibitor induces severe gastric damage . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Two cyclooxygenase ( COX ) isoforms have been identified : COX 1 and COX 2 . ^^^ COX 1 is the constitutively expressed form of the enzyme and is ubiquitous in its distribution . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Shy1p is necessary for full expression of mitochondrial COX 1 in the yeast model of Leigh ' s syndrome . ^^^ The suppressor mutations are in MSS 51 , a gene previously implicated in processing and translation of the COX 1 transcript for subunit 1 ( Cox 1 ) of COX . ^^^ We propose that Shy1p promotes the formation of an assembly intermediate in which Cox 1 is one of the partners . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In conclusion , the neuropeptide alpha MSH has a beneficial effect on endotoxin induced distal intestinal lesions by a mechanism which probably involves nitric oxide and COX 1 derived prostaglandins . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Loss of COX activity was not attributable to reduced rates of mitochondrial protein synthesis or declines in either COX subunit mRNA or protein levels ( COX 1 , 2 , 4 ) . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ In the biodistribution experiments , 18F SC 63217 showed much higher uptake in the small intestine ( an organ known to express high levels of COX 1 ) than did 18F SC 58125 . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ There was no significant apoptotic cell death in normal and specific COX 1 inhibitor ( SC 560 ) treated epididymal cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed as a `` housekeeping ' ' enzyme in most tissues . ^^^ 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 P20674	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 . ^^^ In contrast , TXA ( 2 ) was markedly suppressed by the COX 1 inhibitor SC 560 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
This study was designed to investigate the expression and molecular signaling of cyclooxygenase 1 ( COX 1 ) in cervical carcinomas . ^^^ Real time quantitative reverse transcription polymerase chain reaction and Western blot analysis confirmed enhanced expression of COX 1 RNA , and protein in squamous cell carcinomas and adenocarcinoma of the cervix . ^^^ COX 1 expression in all carcinoma tissues was associated with enhanced expression of COX 2 RNA and protein . ^^^ The site of COX 1 expression was localized by immunohistochemistry to the neoplastic epithelial cells in all squamous cell carcinomas and adenocarcinomas studied . ^^^ Minimal COX 1 immunoreactivity was detected in normal cervix . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Two isoforms of this enzyme have been identified : constitutive COX 1 and inducible COX 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 was detected in polyps and the adjacent normal tissues by Western immunoblotting , but neither COX 1 nor leukocyte type 12 lipoxygenase , the murine ortholog to human 15 lipoxygenase 1 , was detected . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 ) . ^^^ COX 1 is implicated in the regulation of many physiological functions . ^^^ Inhibition of COX 1 explains most of the classical side effects of non selective NSAID . 4 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Oxidant exposure rapidly produced a large mtDNA deletion involving the coding regions for cytochrome c oxidase ( COX 1 ) and NADH dehydrogenase ( ND 1 and ND 2 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Compound 4 showed the highest COX 1 inhibitory activity at 100 microg / mL . ^^^ All the compounds tested gave good COX 1 and moderate COX 2 enzyme inhibitory activities at 100 microg / mL . ^^^ This is the first report of COX 1 and 2 inhibitory activities for compounds 1 5 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ These results demonstrate that COX 1 contributes to the oedema and the formation of PGE ( 2 ) and TXB ( 2 ) in rat CIA model , but not in rat AIA model . ^^^ We conclude that FR 122047 has an orally active and anti inflammatory effect mediated by inhibition of PGE ( 2 ) and TXB ( 2 ) produced by COX 1 at a site of inflammation induced by type 2 collagen and it may be a useful tool for studying the involvement of COX 1 in various in vivo models of inflammation . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Mucosal damage produced by 150 mmol / L HCl and 60 % ethyl alcohol did not increase COX 1 mRNA expression in any age group . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ RESULTS : COX 1 was expressed mostly in nonvascular smooth muscle with weak reactivity in malignant and nonmalignant urothelium . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We recently reported that there was enhanced cyclooxygenase ( COX ) 2 expression and prostaglandin E ( 2 ) biosynthesis in COX 1 deficient ( COX 1 ( / ) ) cells . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 protein levels were found to be unchanged in kidneys from cirrhotic rats . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
There are at least two different isoforms of the enzyme known as COX 1 and 2 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ A selective COX 1 inhibitor ( SC 560 ) did not cause damage , despite reducing PGE 2 content . ^^^ 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 P20674	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 % . ^^^ Meloxicam inhibited COX 1 from 30 to 55 % depending on the repetition of the dose and increase in plasma concentrations . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ By contrast , COX 1 mRNA was largely unaffected by the drug treatments in all tissues studied . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Levels of the constitutive COX isozyme , COX 1 , were not altered by the various treatments in the cell systems studied . ^^^ 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 P20674	Pubmed	SVM Score :0.0
A serious side effect of COX 1 and COX 2 is renal damage . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Nonsteroidal anti inflammatory drugs ( NSAIDs ) are nonselective inhibitors of cyclooxygenase ( COX ) isoforms COX 1 and COX 2 . ^^^ Despite their good efficacy , NSAIDs are associated with significant gastrointestinal ( GI ) toxicity , which appears to be related to the inhibition of the cytoprotective function of COX 1 . ^^^ 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 P20674	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 . ^^^ Increased synthesis of this vasodilatory and antithrombotic PG represents a homeostatic response during periods of accelerated platelet vessel wall interactions and counteracts increased synthesis of COX 1 derived prothrombotic prostanoid thromboxane A ( 2 ) ( TXA ( 2 ) ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Furthermore , selective inhibition of COX 1 via post training piroxicam administration had no effect on retention of either task . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ In contrast , fewer adenocarcinomas tended to show Cox 1 expression compared with squamous cell carcinomas ( 4 of 51 adenocarcinomas [ 8 % ] vs . 9 of 46 squamous cell carcinomas [ 20 % ] ; P = 0 . 14 ) . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The disease runs a protracted course , even if COX 1 inhibitors are avoided . ^^^ To prevent life threatening reactions , patients with AIA should avoid aspirin and other analgesics that inhibit COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Thromboxane B 2 ( TXB 2 , the stable metabolite of TXA 2 ) was measured as a likely indicator of COX 1 activity . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ COX 1 level was significantly lower in the HFF group than the other three groups ( p < 0 . 001 ) . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Two isoforms of this enzyme COX 1 and COX 2 are known to exist . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ On the other hand , another study indicated that COX 1 also plays an important role in the early stage of intestinal tumorigenesis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
BACKGROUND : Interaction with platelet function by non steroidal anti inflammatory drugs ( NSAIDs ) is related to the inhibition of cyclo oxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ We found that COX 1 protein was constitutively expressed in lung tissue . ^^^ 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 P20674	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 P20674	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 P20674	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 . ^^^ Similarly , the selective COX 1 inhibitor SC 560 also caused no gastric damage , despite inhibiting PGE 2 production . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In conclusion , this study demonstrates that primary tumors negatively impact DC development and function through COX 1 and 2 regulated factors , whereas tumor derived cell lines may lose this ability upon in vitro propagation . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Two abietane diterpenes , aethiopinone and 11 , 12 dihydroxy 6 oxo 8 , 11 , 13 abietatriene and the rosane lagascatriol showed a remarkable effect on COX 1 pathway of PGE 2 release in calcium ionophore A 23187 stimulated peritoneal macrophages . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Gastrin mRNA remained detectable only in antrum mucosa , CCKB R mRNA in corpus mucosa and COX 1 mRNA both in antrum and corpus mucosa . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Given the role of COX and PG during intrathymic T cell development in the mouse , we investigated the expression and localization of these isozymes in the human thymus . mRNA and proteins correspondent to COX 1 and 2 were observed from whole thymus extracts . ^^^ By contrast , COX 1 was diffusely and exclusively present in the cortex , both in thymocytes at early stages of differentiation and in cytokeratin positive epithelial cells , as demonstrated by double immunostaining and flow cytometry analysis . ^^^ The inducible isoform of the PGE ( 2 ) synthase was also present in the same cells , while was absent from COX 1 expressing cells of the cortex . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We have investigated the expression and activity of COX 1 and 2 during human megakaryocytopoiesis . ^^^ 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 P20674	Pubmed	SVM Score :0.0
These results suggest that in rat colon only the COX 1 enzyme is expressed under basal conditions . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In mucosa adjacent to an invasive gastric adenocarcinoma , expression of cyclooxygenase was prominent , with COX 1 primarily in mucosal T lymphocytes surrounding nests of tumor cells . ^^^ Densitometry showed these tumor adjacent cells had substantial levels of COX 1 immunoreactive protein ( relative intensity , 3 . 2 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Group 1 introns were found in the cob and cox 1 genes of Volvox carteri . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 staining was present in normal stomach and in ulcerated areas . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cap markedly suppressed the expression of COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
A semi quantitative RT PCR method was then adopted to evaluate the mRNA expression of cytochrome oxidase subunit 1 ( COX 1 ) in the retina after surgery . ^^^ Up regulation of COX 1 mRNA in the retina was detected by RT PCR at 24 hr following the optic nerve injury . ^^^ In conclusion , both the expression of COX 1 mRNA in retina and the activity of COX in inner plexiform layer and retinal ganglion cell layer were elevated following optic nerve injury without affecting total retinal mitochondrial mass . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and 2 expression during the terminal phase of kidney development is poorly understood . ^^^ 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 . ^^^ Within the matured cortical collecting duct ( CCD ) COX 1 and 2 immunoreactivity could not be detected . ^^^ In contrast , a heterogeneous expression profile for COX 1 and 2 is found in the outer medullary CD ( OMCD ) , since not all cells showed immunohistochemical labeling . ^^^ 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 P20674	Pubmed	SVM Score :0.0
There was no expression of COX 1 , either mRNA or protein , on any day of the estrous cycle . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The COX enzymatic system includes two isoenzymes , COX 1 and COX 2 , that convert arachidonic acid to prostaglandins . ^^^ COX 1 is constitutively expressed and synthesizes cytoprotective prostaglandins in the gastrointestinal tract . ^^^ 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 P20674	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 . ^^^ COX 1 levels were only 1 . 1 fold higher . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast to standard doses of 2 nonsteroidal antiinflammatory drugs ( NSAIDs ) , a supratherapeutic valdecoxib dosage does not impair platelet function ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Pretreatment with piroxicam ( 0 . 2 2 . 0 mg / kg ) , a COX 1 inhibitor , considerably impaired the nicotine induced ACTH and corticosterone secretion . ^^^ Noradrenaline , stimulating postsynaptic alpha 1 adrenergic receptors , and prostaglandins , synthesized by COX 1 isoenzyme , are of crucial significance in the nicotine induced ACTH and corticosterone secretion . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Short term regulation of basolateral organic anion uptake in proximal tubular OK cells : EGF acts via MAPK , PLA ( 2 ) , and COX 1 . ^^^ 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 . ^^^ Subsequently , arachidonic acid is metabolized to prostaglandins via COX 1 , which then mediate EGF induced stimulation of basolateral organic anion uptake rate . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The COX 1 inhibitor SC 560 accelerated hypotension and death of the LPS animals without affecting the RSNA increase . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
There are two isoforms of COX , namely COX 1 and COX 2 . ^^^ Metabolites derived from COX 1 are involved in cellular housekeeping functions . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ The nitric oxide produced by ecNOS attenuated COX 1 activity in injured arterioles and venules , but carbon dioxide enhanced it , leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition . ^^^ Although a high hydrogen ion concentration was unnecessary for excitation of COX 1 , venule constriction in response to H+ was enhanced by COX 1 inhibition . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Gastric prostaglandins ( PG ) were also assessed as a measure of COX 1 inhibition . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Earlier studies with COX knockout ( COXko ) mice suggested that COX 2 was more important for hypophagia than COX 1 . ^^^ The COX 1 selective inhibitor , SC 560 , attenuated both the early and late responses , but a larger effect at 30 min than at 90 min suggested a role for COX 1 at the earlier time . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Endothelial COX 1 and 2 differentially affect reactivity of MVB in portal hypertensive rats . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Immunocytochemical analysis of tissues collected 7 days after the final MPTP treatment showed that MPTP significantly decreased the number of tyrosine hydroxylase immunoreactive ( TH ir ) neurons in the substantia nigra pars compacta ( SNc ) of WT ( 40 % decrease ) and COX 1 ( / ) ( 45 % decrease ) mutants . ^^^ 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 P20674	Pubmed	SVM Score :0.0
No alterations in the ratio of 16S rRNA to COX 1 mRNA were detected , nor was there an accumulation of unprocessed mtDNA transcripts . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The current study examined further whether COX 1 is also involved in mediating ACEI induced renin production . ^^^ Therefore , we investigated if genetic deletion of COX 1 or EP ( 2 ) prevents increased ACEI induced renin expression . ^^^ There were no significant differences in the basal level of renal renin activity from plasma or renal tissue in COX 1 + / + and / mice . ^^^ This study provides definitive evidence that metabolites of COX 2 rather than COX 1 mediate ACEI induced renin increases . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ We therefore investigated whether a COX 1 selective inhibitor , mofezolac , suppresses intestinal carcinogenesis in rodents . ^^^ The data indicate that both COX 1 and COX 2 can contribute to intestinal tumorigenesis . . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ In contrast , the inhibition of COX 1 during pregnancy lacked these prenatal and postnatal adverse effects on the DA and effectively delayed the initiation of full term labor and LPS induced preterm labor . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 levels were significantly higher in malignant HMECs than in nonmalignant HMECs . ^^^ These results suggest that COX 1 expression and its inhibition play a role in the choline phospholipid metabolism of HMECs , and the effect of indomethacin on HMECs may be mediated , in part , through upregulation of nm23 . . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ Our data indicate that endogenous progenitor COX 1 mRNA levels are low and are not regulated by IL 1beta . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , there was no substantial change in the expression of Cox 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ COX 1 enzyme is expressed constitutively in most cells and tissues . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The clinical usefulness of nonselective nonsteroidal anti inflammatory drugs ( NSAIDs ) is often limited by the occurrence of adverse effects , such as gastric toxicity and bleeding complications , which have been attributed to the inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) is crucial in inflammation ; COX 1 is constitutional , and COX 2 is inducible . ^^^ In this study , neurological function and infarct volume were evaluated at 24 h after permanent endovascular middle cerebral artery occlusion ( MCAO ) in both COX 1 gene knockout ( homozygous or heterozygous ) and wide type mice . ^^^ Our results failed to confirm the harmful effect of losing COX 1 activity due to gene knockout in a permanent endovascular MCAO mouse stroke model . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Immunohistochemistry study showed that both COX 1 and 2 were localized to nonciliated epithelia and tubal smooth muscle . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
All of the tested THPs exhibited COX 1 and COX 2 nonselective inhibition . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Constitutive COX 1 protein expression was unchanged . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Because nonselective cycloooxygenase ( COX ) inhibition attenuated anorexia after lipopolysaccharide ( LPS ) administration , we tested the ability of resveratrol ( 2 . 5 , 10 , and 40 mg / kg ) and NS 398 ( 2 . 5 , 10 , and 40 mg / kg ) , selective inhibitors of the two COX isoforms COX 1 and 2 , respectively , to attenuate LPS ( 100 microg / kg ip ) induced anorexia . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 and the Ca ( 2+ ) independent iPLA ( 2 ) ( type 6 ) were unaffected by lithium . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Inhibition of COX 1 and 2 by specific inhibitors ( SC 560 , SC 236 ) inhibited the prostanoid release between 50 80 % and 20 40 % , respectively , indicating a predominant role for COX 1 . ^^^ These results indicate , that the functional coupling of COX 1 and 2 to final prostanoid synthases depends on the stimulation of the cells . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
However , they also have major fetal side effects that seem to be due to COX 1 inhibition . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ In the normal mouse retina , COX 1 immunoreactivity is present in the outer segments of photoreceptor cells , horizontal cells , microglia , retinal ganglion cells , and displaced amacrine cells . ^^^ In the normal rat retina , COX 1 immunoreactivity is present in microglia , retinal ganglion cells , and displaced amacrine cells . ^^^ In the normal human retina , COX 1 immunoreactivity is present in microglia , astrocytes , retinal ganglion cells , and displaced amacrine cells . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ These results suggest that COX 1 and cNOS play as the respective key enzyme responsible for producing PG and NO following the duodenal acidification , both of which are involved in the mechanism for the acid induced HCO 3 secretion in the duodenum . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Two cyclooxygenase isozymes , COX 1 and 2 , are known to catalyze the rate limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs . ^^^ Here we describe a third distinct COX isozyme , COX 3 , as well as two smaller COX 1 derived proteins ( partial COX 1 or PCOX 1 proteins ) . ^^^ COX 3 and one of the PCOX 1 proteins ( PCOX 1a ) are made from the COX 1 gene but retain intron 1 in their mRNAs . ^^^ PCOX 1 proteins additionally contain an in frame deletion of exons 5 8 of the COX 1 mRNA . ^^^ Intron 1 is conserved in length and in sequence in mammalian COX 1 genes . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The beginning of the nineties gave the evidences , that two cyclooxygenase isoforms existed : COX 1 and COX 2 . ^^^ The blockage of COX 1 in consequence cause the adverse effects of NSAIDs . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
PGE ( 2 ) synthesis in this podocyte cell line increased fourfold at 60 min in response to PMA , coinciding with upregulation of cyclooxygenase ( COX ) 2 but not COX 1 levels . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Until recently , COX 1 was considered responsible for the synthesis of renal prostaglandins . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Studies with selective inhibitors highlighted the importance of the cox 1 isoform in prion induced neurotoxicity . ^^^ The cox 1 inhibitors also inhibited neuronal PGE production and protected both neuroblastoma cells and primary cortical neurones against prions . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Unlike most other mammalian cells , beta cells of Langerhans constitutively express cyclooxygenase ( COX ) 2 rather than COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition with ibuprofen and nimesulide ( COX 2 selective ) was instituted . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Pregnancy specifically increased COX 1 and PGIS protein expression in the myometrial tissues before labor ( P < 0 . 01 for both ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E ( 2 ) , while the expression level of COX 1 was unchanged . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : Expression of COX 1 mRNA did not change in response to hypoxia in the cortex or medulla in either infantile or adult rats . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 was expressed intensely in the microglia but weakly in the neurons in control brains . ^^^ These COX 1 immunoreactive microglia showed a more activated form following ischemic damage and hypoxemia . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Similar inhibition was observed using a COX 1 inhibitor ( SC 560 ; 10 mg kg ( 1 ) I . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Suppression of concentrations of PGE 2 in the gastric mucosa and TXB 2 in blood by aspirin administration is consistent with activity against COX 1 . ^^^ Meloxicam , in contrast , had a minimal effect on functions mediated by COX 1 . ^^^ CONCLUSIONS AND CLINICAL RELEVANCE : Meloxicam acts in vivo in dogs as a COX 1 sparing drug on target tissues by sparing gastric PGE 2 synthesis while retaining antiprostaglandin effects within inflamed joints . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Here COX 1 and LO activity were measured respectively by the formation of thromboxane B ( 2 ) ( TXB ( 2 ) ) or leukotrienes ( LT ) C ( 4 ) , D ( 4 ) and E ( 4 ) in whole blood stimulated with A 23187 . ^^^ 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 . ^^^ Aspirin , indomethacin and nimesulide inhibited COX 1 activity , without altering LO activity . ^^^ NO aspirin , like aspirin inhibited COX 1 activity in blood from both groups . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , an enzyme essential for prostaglandin biosynthesis , has two isoforms , COX 1 and 2 . ^^^ In contrast , localization of COX 1 protein and mRNA , as well as the amount of protein expression , showed no significant change during wound healing . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) enzyme system is composed of two isoenzymes , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
That is , other more rapid mechanisms , which involve the constitutive COX 1 isozyme , may be more critical for a PG dependent fever . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 is constitutively expressed in most tissues and cells in animal species . ^^^ The COX 1 promoter region lacks a canonical TATA or CAAT box and is GC rich . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , a selective COX 1 inhibitor , SC 560 , did not measurably reduce tumor prostaglandin levels or tumor growth despite the presence of COX 1 in the host and tumor cells . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Rat blood , unlike human blood , may also produce copious amounts of PGE 2 via the actions of COX 1 enzyme constitutively present in platelets . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In hypoxia inhibited and stimulated cells , Western blotting revealed hypoxic induction of cyclooxygenase ( COX ) 2 , which was dependent on the activation of p 38 ( MAPK ) , but not COX 1 , inducible nitric oxide synthase ( iNOS ) , or hemoxygenase 1 ( HO 1 ) . ^^^ 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 P20674	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 P20674	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 . ^^^ The prevalent theory about the pathogenesis of urticaria and angioedema due to NSAIDs in cross reactive patients assumes that the inhibition of COX 1 leads to a shunting of arachidonic acid metabolism towards the 5 lipoxygenase pathway , which results in an increased synthesis and release of cysteinyl leukotrienes . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
To assess the compound potency on canine enzymes , canine COX 1 and COX 2 were cloned , expressed , and purified . ^^^ Cyclooxygenase 1 was cloned from a canine kidney complementary DNA ( cDNA ) library , with 96 % sequence homology to human COX 1 . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) occurs in two forms ( COX 1 and 2 ) and acts as the rate limiting enzyme that generates prostaglandin H ( 2 ) . ^^^ COX 1 is produced as a steady state enzyme , while COX 2 is heavily involved in inflammation and tumorigenesis . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In thrombin or ionophore stimulated human platelets , hyperforin suppressed COX 1 product ( 12 ( S ) hydroxyheptadecatrienoic acid ) formation with an IC ( 50 ) of 0 . 3 and 3 microM , respectively , being about 3 to 18 fold more potent than aspirin . ^^^ At similar concentrations , hyperforin suppressed COX 1 activity in platelets in presence of exogenous AA ( 20 microM ) as well as in cell free systems . ^^^ We conclude that hyperforin acts as a dual inhibitor of 5 LO and COX 1 in intact cells as well as on the catalytic activity of the crude enzymes , suggesting therapeutic potential in inflammatory and allergic diseases connected to eicosanoids . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Inhalation of NO during endotoxemia increased the constitutive COX ( COX 1 ) expression , and the circulating TxB ( 2 ) and PGF ( 2alpha ) increased further after INO withdrawal . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
However , no significant changes were observed in COX 1 levels at any cyanide concentration . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Two isoforms of COX are known : COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Treatment of infected tissue with selective COX inhibitors revealed that COX 1 and 2 must be blocked to restore electroneutral sodium absorption , although the transporter involved did not appear to be the expected Na ( + ) / H ( + ) exchanger 3 isoform . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 mRNA was constitutively expressed . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The inhibition of COX 1 enzyme by the fatty acid fraction and compounds 1 3 at 250 microg / mL were 98 , 37 , 55 , and 67 % , respectively . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
By contrast , a COX 1 selective inhibitor , mofezolac , did not lower MBP . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 enzymes were found only in the particulate fractions , with COX 1 87 % higher in 6 month old CD 1 pcy / pcy mice compared with normal controls , and 110 % higher in male 70 day old Han : SPRD cy rats with cystic kidneys compared with controls . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
We used in situ and in vitro techniques to define the lineage , number , per cell enzyme content , and epithelial functional effect of prostaglandin generating cells , identified by the presence of cyclooxygenase 1 ( COX 1 ) . ^^^ Three populations of COX 1 ( + ) mucosal cells were identified , based on their morphology and local distribution in human mucosa ; these were in the intra epithelial , crypt apical , and lamina propria regions , with each containing a similar amount of COX 1 protein on a per cell basis . ^^^ The most numerous were COX 1 ( + ) mononuclear cells in the lamina propria , identified as CD 3 ( + ) T lymphocytes , both in situ and ex vivo . ^^^ In toto , 21 % of lamina propria mononuclear cells were COX 1 ( + ) , and over 50 % of these cells were CD 3 ( + ) T cells . ^^^ Using established surface markers , intra epithelial and crypt apical COX 1 ( + ) cells were non lymphoid CD 45 ( + ) leukocytes ; neither IgA ( B lymphocytes ) nor alpha smooth muscle actin ( myelofibroblasts ) was co expressed on these COX 1 ( + ) cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Prostaglandins ( PGs ) E 2 and I 2 were measured in the homogenates to assess the activity of COX 1 . ^^^ 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 . ^^^ Paracetamol , 100 mg / kg , inhibited COX 1 in stomach mucosa ex vivo much less effectively than in other tissues . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Pretreatment with piroxicam ( 0 . 2 2 . 0 mg / kg ) , a COX 1 inhibitor , considerably diminished the nicotine induced ACTH and corticosterone secretion in control and crowded rats . ^^^ 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 P20674	Pubmed	SVM Score :0.0
In addition , platelet aggregation by co addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C ( PLC ) inhibitor ( U 73122 ; IC50=0 . 2 micromol / L ) , the MAP kinase inhibitor , PD 98059 ( IC50=3 micromol / L ) , and cyclooxygenase ( COX 1 ) inhibitors including indomethacin ( IC50=0 . 25 micromol / L ) , flurbiprofen ( IC50=0 . 7 micromol / L ) , and piroxicam ( IC50=7 micromol / L ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Immunoblot analysis showed a 60 % reduction of COX 1 and COX 2 polypeptides . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ But COX 1 mRNA was expressed constitutionally in all of the fresh cancer tissue samples . ^^^ In contrast , COX 1 protein was mainly localized at smooth muscle cell of normal tissue and cystitis tissue ( positive rate was 100 % ) but was not expressed in cancer tissue . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Preincubation of COX 1 with inhibitor for 5 min yielded IC ( 50 ) values of 18 microM for TriAcSHA and 60 microM for acetylsalicylic acid . ^^^ As with aspirin , mutation of the serine 530 of COX 1 to alanine abolished the activity of the TriAcSHA . ^^^ The diacetylated phenylhydroxamates N methyl O , O diacetylsalicylhydroxamic acid , N , O diacetylbenzohydroxamic acid , and 2 methyl O , N diacetylbenzohydroxamic acid showed reduced or absent activity against COX 1 . ^^^ All of the compounds inhibited COX 1 and demonstrated progressively greater COX 1 selectivity with increasing number of carbons . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Meloxicam ( Mobic ) is a new nonsteroidal anti inflammatory drug ( NSAID ) derived from enolic acid , exhibiting selectivity for cyclooxygenase ( COX ) 2 over COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
SC 560 , a selective COX 1 inhibitor , had no effect on growth of either cell lines . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Sarcoma 180 cells implanted in wild type ( WT ) mice formed a tumor with extensive angiogenesis , which was greatly suppressed by specific inhibitors for cyclooxygenase ( COX ) 2 but not for COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , cortical COX 1 expression was constant , but medullary COX 1 expression increased eightfold from the 1st to 4th postnatal week . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ L 1 for COX 1 . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
STUDY POPULATION : Purified ovine COX 1 and 2 and cultures of RAW 264 . 7 murine macrophages . ^^^ PROCEDURE : The COX 1 and 2 inhibitory effects of the NSAIDs were tested in assays that used purified ovine COX 1 and 2 . ^^^ RESULTS : Flunixin meglumine and phenylbutazone were selective inhibitors of COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , cox 1 was expressed only in vegetative cells . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 mRNA expression was not found in granulosa cells at 3 h but was found in these cells at 9 h . ^^^ In the oviduct , the expression of EP 4 and COX 1 mRNA was localized to epithelial cells , whereas expression of EP 2 mRNA was localized to the smooth muscle layer . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Focal regions within the tumor expressing high COX 1 also had elevated levels of pro angiogenic proteins . ^^^ 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 ) . ^^^ Thus , COX 1 may contribute to carcinoma development in the ovary through stimulation of neovascularization . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The expression of cyclooxygenase ( both COX 1 and COX 2 ) has also been examined immunohistologically . ^^^ Levels of COX 1 were higher after surgery in both animals . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Possible reasons for the disparity between marked COX 1 inhibition and the limited effect on the cardinal signs of inflammation are considered . ^^^ Administration of both enantiomers again produced marked and prolonged inhibition of platelet COX 1 and , in the case of R ( ) KTP , this was probably attributable to S ( + ) KTP formed by chiral inversion . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Through use of ET ( A ) and ET ( B ) antagonists ( BQ 610 and BQ 788 , respectively ) , the contribution of the ET receptors to COX 1 and 2 expression and ppET 1 gene expression was examined . ^^^ 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 P20674	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 . ^^^ Only one of the 1 ( p methylsulfonylphenyl ) pyrazole compounds ( 16 ) displayed a modest inhibitory activity towards both type of isoenzymes , while the pyrazole 1 ( p aminosulfonylphenyl ) substituted 12 proved to be significantly active only towards COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In COX 1 and 2 enzyme inhibitory assays , compounds 1 3 ( all at 80 microM ) showed activities of 20 . 4 , 46 . 3 % ; 57 . 6 , 47 . 9 % ; and 8 . 2 , 13 . 7 % , respectively , compared to naproxen ( 54 . 3 , 41 . 3 % ; 10 microM ) , ibuprofen ( 47 . 5 , 39 . 8 % ; 10 microM ) , Celebrex ( 46 . 2 , 66 . 3 % ; 1 . 67 ppm ) , and Vioxx ( 23 . 8 , 88 . 1 % , 1 . 67 ppm ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and 2 play functionally distinct roles in lymphocyte development , and consequently , genetic deficiency of either enzyme , as opposed to acute pharmacologic inhibition , may modulate Th 2 mediated allergic airway disease differently . ^^^ The airways of COX 1 / mice contained increased numbers of CD4+ and CD8+ T cells , exaggerated levels of the Th 2 cytokines interleukin 4 , 5 , and 13 , and increased levels of eotaxin and thymus and activation regulated chemokine . ^^^ Allergen induced bronchoconstriction was also increased in COX 1 / mice . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
There are two isoforms of COX , referred to as COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
So far NSAIDs caused mucosal injury was attributed to their inhibitory effects on the activity of cyclooxygenase 1 ( COX 1 ) which is expressed and shown to play a crucial role for the mucosal protection via producing prostaglandin E 2 in the stomach . ^^^ 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 . ^^^ COX 1 inhibition alone has been demonstrated not to cause gastric mucosal injury . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ As in many other cell types , COX 1 expression in renal medulla is unlikely subject to robust regulation . ^^^ 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 P20674	Pubmed	SVM Score :0.0
There were no significant differences among vehicle or DFU treated groups in [ ( 3 ) H ] inulin clearance , or in glomerular expression of COX 1 and 2 . ^^^ However , inhibition of both COX 1 and 2 is required to achieve a maximum cytoprotective and antiproteinuric effect . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ RESULTS : COX 1 expression was similar in normal and control GI tissues . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The relative importance of COX 1 and COX 2 isoforms is under active investigation . ^^^ We have performed a comprehensive histochemical analysis by comparing rat and mouse kidneys for cellular and subcellular localization of COX 1 and 2 and microsomal type PGE synthase ( PGES ) , the rate limiting biosynthetic enzyme in PGE 2 synthesis . ^^^ In the glomerulus , significant COX 1 expression was detected in a subset of mesangial cells . ^^^ 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 . ^^^ Cortical fibroblasts were COX 1 and PGES positive in mice , whereas in rats only PGES could be reliably detected . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In contrast , COX 1 was relatively ubiquitously observed in both normal and pathophysiological conditions . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Engagement of EC alphavbeta 3 by vitronectin ( versus fibronectin or gelatin ) or by monoclonal antibodies ( mAbs ) LM 609 and LIBS 6 , enhanced PGI 2 generation and also induced expression of both COX 1 and 2 isoforms . ^^^ 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 . ^^^ COX 1 inhibition also prevented new vessel formation in an in vitro model of angiogenesis that is alphavbeta 3 dependent . ^^^ Inhibition of angiogenesis by the COX 1 inhibitor was partially reversed by removal of the inhibitor or by addition of the stable analogue of PGI 2 , iloprost . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ The protective effect of COX 1 is preserved in chronic inflamed colon . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Constitutively expressed cyclooxygenase ( COX 1 ) inhibition is likely to be responsible for the cross reactions and side effects associated with these drugs , as well as the anaphylactoid reactions sometimes seen in aspirin sensitive respiratory disease . ^^^ Thus , an anaphylactoid reaction caused by a particular COX 1 inhibiting NSAID will occur with a chemically unrelated NSAID which also inhibits COX 1 enzymes . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , COX 1 expression was not detected in any specimen . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : Immunoreactivities for COX 1 and 2 were limited to the nasal glands , and no expression was noted in the surrounding vascular endothelial cells , olfactory glands , respiratory epithelium , olfactory epithelium , submucosal tissue or nerves . ^^^ The results demonstrated localization of COX 1 and 2 in uriniferous tubules . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 expression levels were found to be significantly reduced in tumors compared to matched normal tissues ( Dunn ' s method , P < 0 . 05 ) . ^^^ Additionally , COX 1 expression was decreased in stage T 3 tumors as compared to stage T 2 tumors ( Student ' s t test , P = 0 . 009 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , a selective COX 1 inhibitor , SC 560 , had no effect on serum progesterone concentrations . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ RESULTS : In comparison to strong Cox 1 reactivity in airways and endothelial cells of normal lung specimens , only 4 of 15 adenocarcinomas showed infrequent Cox 1 expression . ^^^ 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 P20674	Pubmed	SVM Score :0.0
The findings indicate that the intolerance reaction in AIA is due to inhibition of COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
There was immunohistochemically no significant difference in COX 1 positivity of normal intestinal epithelia and adenomas among three groups . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Mucin assay and western blots for COX 1 and COX 2 were performed . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The most rapidly evolving region of 8 L is one that interacts with COX 1 , suggesting that the changes are functionally coadaptive . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In contrast , the expression of COX 1 or vascular endothelial cell growth factor mRNAs had no significant differences among the groups . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 ) . ^^^ RESULTS : Prostaglandins are derived from COX 1 activity in the normal esophagus . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In conclusion , unlike ibuprofen , valdecoxib 40 mg bid spares platelet COX 1 function in healthy elderly subjects . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , no significant changes in COX 1 mRNA and protein levels were noted . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ No changes were found in COX 1 gene expression after exposure to hypoxia . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In contrast , COX 1 was expressed in 45 % of tumors and was associated with smaller tumor size ( P = 0 . 02 ) and with negative lymph node status ( P = 0 . 01 ) . ^^^ Elevated expression of COX 1 in tumor tissue had no statistically significant influence on patient prognosis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Unstimulated IMCD released moderate , but significant , amounts of PGE 2 , which were more sensitive to cyclooxygenase ( COX ) 2 than COX 1 inhibition . ^^^ 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 . ^^^ If it is assumed that increased release of PGE 2 is related to its increased production , our results suggest that purinergic stimulation of IMCD results in enhanced production and release of PGE 2 in a COX 1 dependent fashion . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The underlying mechanisms of gastric injury include topical irritant actions that disrupt the epithelial barrier , as well as the inhibition of cyclo oxygenase ( COX ) , which is predominantly the COX 1 isoform in the mucosa . ^^^ 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 P20674	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 . ^^^ In contrast , the COX 1 inhibitor resulted in a profound hypothermic response to LPS and blocked LPS induced Fos immunoreactivity in the PVH , PB , NTS , and VLM , although it had no effect on the VMPO . ^^^ LPS , at least some components of the response , including avoiding hypothermia and the induction of Fos in the NTS , VLM , PB , and PVH , appear to depend on COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The present study investigated the importance of prostaglandins ( PG ) formed by cyclo oxygenase isoforms ( COX 1 and 2 ) for the exercise related increase in blood flow in connective tissue . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
There are two forms of COX , COX 1 and COX 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) , which is present in two isoforms ( COX 1 and 2 ) , synthesizes prostaglandins from arachidonic acid ; it plays a crucial role in inflammation in both central and peripheral tissues . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We quantified mitochondrial DNA ( mtDNA ) , expression of nuclear ( COX 4 ) and mitochondrial ( COX 1 ) encoded cytochrome c oxidase subunits as well as nuclear factors involved in mitochondrial biogenesis and in the necessary coordinated interplay between nuclear and mitochondrial genomes in health and CHF . ^^^ CHF induced a decrease in oxidative capacity and mitochondrial enzyme activities with a parallel decrease in the mRNA level of COX 1 and 4 , but no change in mtDNA content . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 immunostaining was identified intracytoplasmically in normal urothelium and in 15 of 20 neoplastic specimens . ^^^ COX 1 immunosignal in the tumor cells was either absent or weak . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The inhibition values of COX 1 enzyme by FAF and 1 3 at 100 microg / ml were 80 , 39 , 19 , and 57 % , respectively . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Both RA isomers caused the enhancement of PGE 2 production and the up regulation of COX 1 expression at the protein and mRNA levels . ^^^ The increase in COX 1 mRNA was found to precede the increase in COX 1 protein expression . ^^^ We conclude that treatment of U 937 cells by RA for 48 h caused the initiation of cell differentiation , which was found to be concomitant with a significant increase in PGE 2 production mediated via the up regulation of COX 1 mRNA and protein expression . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 mRNA was moderately abundant in embryos throughout organogenesis . ^^^ Correlation of COX 1 and CA 4 expression with ASA sensitivity suggested that embryonic COX 1 and possibly CA 4 are much more likely candidates for mediators of ASA developmental toxicity . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We investigated the role of COX isoforms in this model by examining the expression of COX 1 and the effect of intrathecal COX inhibitors . ^^^ Rats were perfused at 1 , 2 , 3 , 5 , and 7 days after incision , and COX 1 immunohistochemistry was performed on L 3 to S 2 spinal cord and gracile nucleus sections . ^^^ 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 . ^^^ COX 1 immunoreactivity increased in glia in the ipsilateral L 4 L6 spinal dorsal horn and ipsilateral gracile nucleus after incision . ^^^ Mechanical allodynia peaked on postoperative day 1 , and COX 1 immunoreactivity increased on day 1 , peaked on day 2 , and declined thereafter . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 expression was induced in macrophages ( Mphis ) , whereas COX 2 was induced in neutrophils . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Immunoblotting and morphological analysis demonstrated that dexamethasone induced neuronal differentiation through COX 1 induction . ^^^ Taken together , COX 1 appears to play an important role in dexamethasone mediated neuronal differentiation . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The physiology and pathophysiology of both COX isoforms ( COX 1 , COX 2 ) are also discussed . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
One hypothesis is that COX 1 inhibition may play a relevant pathogenic role . ^^^ If so , drugs that are not active on COX 1 would be expected to be well tolerated by CU patients . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Originally , it was believed that this isoform was expressed at sites of inflammation but not in noninflamed tissue , where a constitutively expressed isoform , COX 1 , was thought to be responsible for the physiological production of eicosanoid mediators . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
PG production is dependent on the activity of cyclooxygenases ( COX 1 AND 2 ) and PG synthases . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Addition of LXA ( 4 ) , ZD 2138 and U 75302 inhibited these changes . ( 7 ) The present results support the notion that inhibition of ATL formation is mechanistically linked to the reversal of the antiadhesive activity of aspirin caused by selective COX 1 inhibitors and suggests that the LTB ( 4 ) / ATL balance modulates pro and antiadhesive activity of nonsteroidal anti inflammatory drugs at the leukocyte endothelial cell interface . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and 2 , intestinal integrity , and pathogenesis of nonsteroidal anti inflammatory drug enteropathy in mice . ^^^ BACKGROUND & AIMS : The pathogenesis of nonsteroidal anti inflammatory drug induced enteropathy is controversial , but it is thought that cyclooxygenase 1 ( COX 1 ) inhibition is of pivotal importance . ^^^ 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 . ^^^ RESULTS : COX 1 ( / ) animals were normal except for a 97 % decrease in intestinal PGE ( 2 ) levels . ^^^ COX 1 ( + / + ) and COX 1 ( / ) animals reacted in a similar way to indomethacin . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
These observations strongly suggest that capsaicin sensitive sensory neurons might release CGRP , thereby increasing the gastric tissue levels of PGI 2 and PGE 2 by activating COX 1 through activation of the constitutive form of NOS in rats subjected to WIR . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Organ sparing is considered the result of preservation of homeostatic COX 1 enzyme function . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
No significant inhibition of COX 1 is observed with rofecoxib up to doses of 1000 mg . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The mRNA expression of COX 1 in PMNLs was decreased by clarithromycin and azithromycin . ^^^ Macrolide antibiotics inhibited PGE 2 synthesis in human leukocytes by suppressing cPLA 2 , COX 1 , and COX 2 mRNA expression . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Northern blot analysis revealed an increase in COX 1 mRNA after 6 , 12 and 24 h in the jejunum of VMH lesioned rats . ^^^ CONCLUSION : VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX 1 in the small intestine . ^^^ Prostaglandins , probably E ( 2 ) , induced by COX 1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The isolated ductus from wild type and COX 1 / mice contracted promptly to indomethacin ( 2 . 8 micro M ) . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 has an important role in the gastric defense mechanism . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , COX 1 immunoreactivity was relatively uniform in Purkinje cell cytoplasm , and was more homogeneous in cells of the granular cell layer and occasionally of the molecular layer . ^^^ COX 1 immunoreactivity was not found on the cell surface . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Five anthocyanidins consisting of cyanidin ( 1 ) , delphinidin ( 2 ) , pelargonidin ( 3 ) , peonidin ( 4 ) , and malvidin ( 5 ) were tested for COX 1 and 2 enzyme inhibitory activities at 40 microM . ^^^ Eleven catechins consisting of ( + ) catechin ( 6 ) , ( ) catechin ( 7 ) , ( + / ) catechin ( 8 ) , ( + ) epicatechin ( 9 ) , ( ) epicatechin ( 10 ) , ( ) epigallocatechin ( 11 ) , ( ) gallocatechin ( 12 ) , ( ) epicatechin gallate ( 13 ) , ( ) catechin gallate ( 14 ) , ( ) epigallocatechin gallate ( 15 ) , and ( ) gallocatechin gallate ( 16 ) were tested for inhibitory effects of COX 1 and 2 enzymes at 80 microM . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 ) . ^^^ In contrast , the selective COX 1 inhibitors , FR 122047 ( 1 [ ( 4 , 5 bis ( 4 methoxyphenyl ) 2 thiazoyl ) carbonyl ] 4 methylpiperazine hydrochloride ) and SC 560 ( 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ) , had no effect in mouse CIA model . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The extent and intensity of immunoreactive COX 1 and 2 polypeptides in the TC tissues was statistically greater than the expression in the NT tissues . ^^^ 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 P20674	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 . ^^^ H . pylori infection increased levels of mRNA for COX 1 and 2 in gastric tissue by 1 . 2 fold and 3 . 3 fold , respectively , accompanied by a significant increase in PGE 2 production by gastric tissue . ^^^ Inhibition of both COX 1 and 2 by indomethacin or concurrent treatment with SC 560 and NS 398 resulted in a stronger increase in MPO activity and apoptosis than inhibition of either COX 1 or 2 alone . ^^^ In conclusion , PGE 2 derived from either COX 1 or 2 is involved in regulation of gastric mucosal inflammation and contributes to maintenance of mucosal integrity during H . pylori infection via inhibition of TNF alpha expression . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
A randomized crossover study was performed in volunteers receiving 100 mg aceclofenac or a sustained release resinate formulation of 75 mg diclofenac to assess the pharmacokinetics and the ex vivo inhibition of COX 1 . ^^^ 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 ) . ^^^ Moreover , ex vivo COX 1 dependent thromboxane B ( 2 ) synthesis was inhibited significantly less by aceclofenac than by diclofenac . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 activity appears to be related to `` constitutive ' ' or `` housekeeping ' ' functions in the gastric mucosa , kidney and platelets . ^^^ 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 . ^^^ The inhibition of COX 1 activity by NSAIDs is related to adverse side effects in general , particularly gastrointestinal toxicity . ^^^ 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 P20674	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 . ^^^ In theory , new molecules that preferentially inhibit the inducible enzyme alone would not affect the housekeeping function of COX 1 but would retain the antiinflammatory action . ^^^ There are some doubts from studies in animal models as to whether some inhibition of COX 1 is also required , but this has not yet been shown in humans . ^^^ 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 P20674	Pubmed	SVM Score :0.0
This inhibitory effect , especially of COX 1 , is suggested as the mechanism underlying NSAID induced hypersensitivity reactions . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ The COX 1 selectivity of the new compounds was tentatively explained by means of a docking study of one of the more active compounds tested on both COX isoenzymes ( 7d ) , which indicated a different number of hydrogen bonding interactions with the Arg 120 of the active sites of the two enzymes , and therefore , an energetically favored interaction ( 3 . 5 kcal / mol ) with COX 1 , compared with COX2 . . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ The COX II / COX 1 ratio for compound 1 was 17 . 68 at 100 microg mL ( 1 ) compared to solvent control . ^^^ Ibuprofen , Naproxen , Aspirin , Celebrex and Vioxx at concentrations of 2 . 06 , 2 . 52 , 180 , 1 . 67 and 1 . 67 microg mL ( 1 ) , respectively , gave COX II / COX 1 ratios of 1 . 13 , 0 . 92 , 0 . 24 , 16 and 75 , respectively . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Western blots of lumbar spinal cord extracts showed increased levels of cyclo oxygenase ( COX ) 2 protein in the dorsal spinal cord of rats with peripheral inflammation ; no change occurred in the level of COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 mRNA and protein were constitutively expressed , whereas COX 2 was highly modulated in uteroplacental tissues throughout pregnancy . ^^^ Temporal and tissue specific expression of PGE 2 and PGF2alpha receptors and COX 1 and 2 at the maternal fetal interface suggests a selective and distinctive role for PGE 2 and PGF2alpha in uterine activities during pregnancy in bovine . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The expression of COX 1 / beta actin in the obstructed kidney was similar to that in the contralateral unobstructed kidney in the cortex and medulla . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
When applied topically on the intact skin , only a high dose treatment of wogonin ( 1000 microg / ear / 3 days ) slightly increased COX 1 and fibronectin mRNA . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 and COX 1 potentiate beta amyloid peptide generation through mechanisms that involve gamma secretase activity . ^^^ To explore the mechanism through which COX may influence A beta amyloidosis , we used an adenoviral gene transfer system to study the effects of human ( h ) COX 1 and hCOX 2 isoform expression on A beta peptide generation . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Both isoenzymes ( COX 1 and COX 2 ) were detected in cultured cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In the present study , the inhibitor sensitivities of purified Cox 1 and 2 were determined in a colorimetric assay using the reducing agent N , N , N ' , N ' tetramethyl p phenylenediamine . ^^^ Similar effects of genapol were observed with inhibitors of Cox 1 . ^^^ 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 P20674	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 P20674	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 . ^^^ In contrast , COX 1 expression was predominantly confined to microglia and no apparent difference was detected between controls and ALS . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation . ^^^ 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 P20674	Pubmed	SVM Score :0.0
There are two COX enzymes , COX 1 and COX 2 . ^^^ COX 1 is expressed constitutively and is part of normal cell metabolic functions . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Investigations have documented two isoforms , COX 1 and COX 2 , encoded by different genes . ^^^ COX 1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions , such as the maintenance of gastric mucosa and regulation of renal blood flow . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In the brain , regional differences in tracer uptake were observed , with high uptake in cortical regions . ( 18 ) F Desbromo DuP 697 did not show any binding to COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In addition , testosterone treatment had no effect on cerebrovascular production of endothelin 1 or prostacyclin nor did it alter protein levels of endothelial NOS or COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Rofecoxib has been shown to spare COX 1 activity ex vivo , in platelets and gastric mucosa , when administered at therapeutic doses or above . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
For instance , COX 1 splice variants ( also known as COX 3 and PCOX 1a ) may broaden the spectrum of COX activities in disease . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
These effects occurred in cells with bi allelic APC mutation ( SW 480 ) , with wild type APC but mono allelic beta catenin mutation ( HCT 116 ) and in cells that lack expression of either COX 1 or 2 ( HCT 15 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The cyclooxygenase ( COX ) 2 inhibitors 5 , 5 dimethyl 3 ( 3 fluorophenyl ) 4 ( 4 methylsulfonyl ) phenyl 2 ( 5II ) furanone ( DFU ) ( 0 . 02 2 mg / kg ) and N [ 2 ( cyclohexyloxy ) 4 nitrofenyl ] methanesulfonamide ( NS 398 ) ( 0 . 01 1 mg / kg ) , the COX 1 inhibitor 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 trifluoromethylpyrazole ( SC 560 ) ( 0 . 05 5 mg / kg ) , and dexamethasone ( 1 mg / kg ) were studied in rats challenged with intragastric acid ( 300 mM HCl ) . ^^^ The COX 1 inhibitor SC 560 induced moderate damage in the acid challenged stomach even without suppression of NO , but damage was aggravated by L NAME . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Adding PGE 2 or infecting cells with a COX 1 transgene did not abrogate piroxicam induced growth inhibition . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 3 , a variant of COX 1 , has been found in canine brain and is inhibited by acetaminophen and dipyrone at physiological concentrations . ^^^ Additionally , other new COX 1 derived proteins called PCOX have been identified that do not make prostaglandins but apparently bind heme and may have other enzymatic properties . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The current study was undertaken to determine whether COX 1 was altered in this model . ^^^ Four weeks after PSNT and 4 h , 4 days , or 2 weeks after SNL , COX 1 immunohistochemistry was performed on the L 2 S2 spinal cord . ^^^ RESULTS : COX 1 immunoreactivity ( COX 1 IR ) was unaffected 4 h after SNL . ^^^ In contrast , 4 days after SNL , the number of COX 1 IR cells increased in the ipsilateral spinal cord . ^^^ COX 1 IR increased in cells with glial morphology in the superficial laminae , but decreased in the rest of the ipsilateral spinal cord 4 weeks after PSNT and 2 weeks after SNL . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
However , COX 1 expression remained unchanged under similar conditions . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and COX 3 inhibitors . ^^^ The antipyretic action of aspirin may be mediated by inhibition of COX 3 in hypothalamic endothelial cells or by inhibition of COX 1 localised close to sensory receptors of peripheral vagal afferents . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Canine COX 3 apparently is identical to the full length form of COX 1 , with the exception that the COX 3 mRNA retains intron 1 . ^^^ Specific RT PCR primers were designed to detect putative rat COX 3 mRNA , and the RT PCR products were sequenced and compared to the known sequence of the rat COX 1 gene . ^^^ 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 P20674	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 . ^^^ Although the production of neuronal prostaglandin E 2 in response to amyloid beta 1 42 was reduced by the presence of COX 1 inhibitors , no neurotoxic effects of prostaglandin E 2 , or any other prostaglandin , were observed . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Inhibition of the COX 1 , but not the COX 2 pathway , attenuated H2O2 induced dilation similarly to indomethacin . ^^^ These results suggest that H2O2 induces endothelium dependent vasodilation through COX 1 mediated release of PGE 2 and also directly relaxes smooth muscle by hyperpolarization through KCa channel activation . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Role of COX 1 and 2 in prostanoid generation and modulation of angiotensin 2 responses . ^^^ In the present study , selective COX 1 and 2 inhibitors attenuated increases in pulmonary arterial pressure and decreases in systemic arterial pressure in response to arachidonic acid but did not alter responses to PGE 1 or U 46619 . ^^^ The selective COX 1 and 2 inhibitors did not modify systemic pressor responses to injections or infusions of ANG 2 or pulmonary pressor responses to injections of the peptide . ^^^ COX 2 inhibitors did not alter , whereas a COX 1 inhibitor depressed , arachidonic acid induced platelet aggregation . ^^^ These data provide evidence in support of the hypothesis that prostanoid synthesis occurs by way of the COX 1 and 2 pathways in the pulmonary and systemic vascular beds but that pressor responses to ANG 2 are not mediated or modulated by these pathways in the rat . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Treatment of the cells with selective COX inhibitors demonstrated that COX 1 was predominantly responsible for the enhanced generation of prostacyclin induced by H . pylori 60190 . ^^^ CONCLUSIONS : H . pylori increased both COX 1 and COX 2 activity in vascular endothelial cells . ^^^ The regulation of COX 1 at the transcriptional level by H . pylori described in this study is a novel finding and calls into question the traditional description of COX 1 as a purely constitutive , housekeeping gene . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Serum TxB ( 2 ) was assessed as an index of platelet COX 1 activity . ^^^ NC 4016 and aspirin inhibited platelet COX 1 comparably while NO donors were ineffective . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
However , pretreatment with SC 560 , a selective COX 1 inhibitor , did not change hyperalgesic response to IL 1beta . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing , neonatal , and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles . ^^^ Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX 1 positive . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Interestingly , NO ASA induced COX 2 expression , although it had no effect on COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We examined the role of COX 1 and 2 on platelet vessel wall interactions and development of atherosclerosis in a murine model . ^^^ 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 . ^^^ Selective inhibition of COX 1 reduced 2 , 3 dinor TXB 2 generation and lesion formation . ^^^ In contrast to lesion development , the selective COX 1 inhibitor had no effect on the regression of evolving lesions . ^^^ CONCLUSIONS : COX 1 plays an important role in the early stages of lesion development in the apoE / knockout model of atherosclerosis , preventing gross lesion formation in the face of continued vascular injury and inflammation . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
A new phylogenetic hypothesis for Euthyneura is proposed based on the analysis of primary sequence data ( mitochondrial cox 1 , trnV , rrnL , trnL ( cun ) , trnA , trnP , nad 6 , and nad 5 genes ) and the phylogenetic utility of two rare genomic changes ( the relative position of the mitochondrial trnP gene , and an insertion / deletion event in a conserved region of the mitochondrial Cox 1 protein ) is addressed . ^^^ The marine basommatophoran pulmonate Siphonaria was placed within opisthobranchs and shared with them the insertion of a Glycine in the Cox 1 protein . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
HepG 2 and Hep3B cells do not express COX 1 or COX 2 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ The COX 1 inhibitors ketoprofen and SC 560 failed to inhibit the HGF / SF induced angiogenic events in vitro and in vivo . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
It is not clear whether cyclooxygenase ( COX ) 2 and / or COX 1 expression is involved in elevated prostaglandin production stimulated by vasopressin in vivo . ^^^ 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 P20674	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 ) . ^^^ The COX 1 inhibitor SC 560 had no protective effect . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The protective effect of TFLLR NH ( 2 ) was abolished by indomethacin or a COX 1 inhibitor but not by ablation of sensory neurons with capsaicin . ^^^ Immunoreactive PAR 1 and COX 1 were expressed abundantly in rat gastric muscularis mucosae and smooth muscle , and the former protein was also detectable in blood vessels . ^^^ CONCLUSIONS : The PAR 1 agonist , given systemically , protects against gastric mucosal injury via COX 1 dependent formation of prostanoids , modulating multiple gastric functions . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ There were no significant differences in COX 1 mRNA expression between the groups . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Among all animals , glomerular and tubular injury were inversely correlated with mtDNA levels , mtDNA encoded respiratory chain activities and with the expression of the mtDNA encoded respiratory chain subunit COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Higher COX 1 expression was noted in 31 ( 41 . 9 % ) of the 74 specimens of normal mucosa , in none of the 40 specimens of dysplastic mucosa and in 15 ( 18 . 8 % ) of the 80 specimens of SCC , the frequency being significantly higher in normal mucosa than in dysplasia or SCC ( p < 0 . 0001 , p = 0 . 0018 , respectively ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
However , no effects on the expression of COX 1 were observed . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 expression is higher than that of COX 3 in both young and aged platelets . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Exposure of human macrophages to mechanical stretch with particles upregulated the expression of cyclooxygenase ( COX ) 2 mRNA but not COX 1 mRNA , this expression resulting in a 97 fold increase in PGE ( 2 ) production compared to the nonstimulated cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Role of thromboxane derived from COX 1 and 2 in hepatic microcirculatory dysfunction during endotoxemia in mice . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
They have the potential advantage to spare COX 1 activity , thus reducing gastrointestinal toxicity , even when administered at high doses to improve efficacy . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Gastrointestinal toxicity has been attributed to the blockade of the COX 1 mediated generation of the cytoprotective prostanoids , such as PGE ( 2 ) and PGI ( 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 P20674	Pubmed	SVM Score :0.0
There was no increase in COX 1 staining in any tumour type . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Unexpectedly , the COX 1 inhibitor SC 58560 also reduced dynorphin A ( 2 17 ) induced , but not NMDA induced , release of prostaglandin E 2 . ^^^ These findings reveal a novel mechanism by which elevated levels of spinal dynorphin seen in pathological conditions may produce hyperalgesia through the release of excitatory amino acids and in part by the activation of a constitutive spinal COX 1 and 2 cascade . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Proinflammatory cytokines enhance COX 1 gene expression in cultured rat glomerular mesangial cells . ^^^ The rat GMC spontaneously expressed type 1 cyclooxygenase ( COX 1 ) , but not COX 2 . ^^^ Interleukin ( IL ) 1beta ( 25 ng / ml ) , IL 8 ( 25 ng / ml ) , growth related oncogene alpha ( GRO , 50 ng / ml ) and tumor necrosis factor alpha ( TNF alpha , 25 ng / ml ) stimulated the COX 1 protein production as demonstrated by Western blot and enhanced PGE 2 synthesis in GMC , beginning on 2 h of incubation , and steadily enhanced TXB 2 synthesis over a 24 h period . ^^^ 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 P20674	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 . ^^^ Among the NSAID , only aspirin has been proven to significantly reduce cardiovascular risk , primarily through inhibition of COX 1 mediated platelet aggregation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
CONCLUSIONS : The increase in TxA ( 2 ) during PTCA is primarily COX 1 dependent , and aspirin alone is effective in suppressing its formation . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 , COX 2 and the topical effect in NSAID induced enteropathy . ^^^ The pathogenesis of NSAID enteropathy is uncertain but inhibition of COX 1 is believed to be of pivotal importance . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
The cells , however , failed to express tumor necrosis factor alpha , COX 1 , and MMP 9 , regardless of the presence of IL 1 beta . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
N and its constituents , the inhibition of the synthesis of Leukotriene B 4 ( LTB 4 ) and Prostaglandin ( PGE 2 ) by 5 lipoxygenase ( 5 LOX ) and cyclo oxygenase 1 and 2 ( COX 1 and 2 ) respectively were examined in vitro . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
A titre of LRPPRC protein was also found in nuclear fractions that could not be easily accounted for by mitochondrial contamination . [ 35S ] Methionine labelling of mitochondrial translation products showed that the translation of COX 1 , and perhaps COX 3 , was specifically reduced in the presence of the mutation . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
RPM constitutively expressed high levels of COX 1 . ^^^ Studies using isoform selective inhibitors and RPM from mice bearing targeted deletions of ptgs 1 and ptgs 2 demonstrated that COX 1 contributes significantly to PG synthesis in RPM , especially during the initial 1 2 h after LPS addition . ^^^ 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 . ^^^ These results demonstrate autocrine regulation of TNF alpha secretion by endogenous PGs synthesized primarily by COX 1 in RPM and suggest that COX 1 may play a significant role in the regulation of the early response to endotoxemia . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In cyclooxygenase ( COX ) 2 ( / ) mice , acetaminophen ( 300 mg / kg ) produced hypothermia accompanied by a reduction in brain PGE ( 2 ) levels , whereas in COX 1 ( / ) mice , the hypothermia to this dose of acetaminophen was attenuated . ^^^ The brains of COX 1 ( / ) mice had approximately 70 % lower levels of PGE ( 2 ) than those of WT animals , and these levels were not reduced further by acetaminophen . ^^^ We propose that acetaminophen is a selective inhibitor of a COX 1 variant and this enzyme is involved in the continual synthesis of PGE ( 2 ) that maintains a normal body temperature . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In l NAME treated mice , however , cerebrovascular COX 1 levels , prostacyclin production , and constriction to indomethacin , as well as eNOS protein , were all greater in estrogen treated animals . ^^^ In vessels from eNOS ( / ) mice , estrogen treatment also increased levels of COX 1 protein and constriction to indomethacin , but no effect on prostacyclin production was detected . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ On the other hand , parental LM 3 cells were able to stimulate neovascularization via COX 1 and arginase products since only indomethacin and Nomega hydroxy L arginine , which diminished PGE 2 and urea synthesis , respectively , also reduced angiogenesis . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
SC 560 , a specific COX 1 inhibitor , suppressed adipogenesis dose dependently , suggesting a role of constitutive COX 1 in the endogenous synthesis of PGs , including PGJ 2 derivatives formed by mature adipocytes with the ability to promote adipogenesis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Dopamine content in striatum ( high performance liquid chromatography HPLC ) , mRNA expression of COX 1 and 2 ( reverse transcriptase polymerase chain reaction technique RT PCR ) , COX 1 and 2 protein content ( immunoblotting ) have been measured on day 1st , 3rd , 7th , 14th and 21st after the injury . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Previous studies of the yeast model of this disease showed that mutant forms of Mss51p , a translational activator of COX 1 mRNA , partially rescue the COX deficiency of shy 1 mutants by restoring normal synthesis of the mitochondrially encoded Cox1p subunit of COX . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ In this study , we used SKH 1 hairless mice in which COX 1 was selectively deleted to examine the role of COX 1 in photocarcinogenesis . ^^^ After UV exposure , 40 60 % less prostaglandin E 2 was detected in COX 1 / animals compared with wild type ( WT ) controls . ^^^ Proliferation was not significantly different in COX 1+ / + , COX 1+ / , and COX 1 / animals . ^^^ When susceptibility to UV induced tumor formation was studied , tumor number , average tumor size , and time of tumor onset in COX 1 / animals were identical to WT controls . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Of particular importance has been the investigation of COX 1 and 2 isozymic functions in cancer , dysregulation of inflammation , and Alzheimer ' s disease . ^^^ 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 P20674	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 . ^^^ Similar partial inhibition of angiogenesis in the cornea model was observed with NS 398 ( 10 or 20 mg kg ( 1 ) day ( 1 ) , s . c . or i . p . ; 54 % inhibition , p < 0 . 001 ) , but not with the COX 1 selective SC 560 ( 10 or 20 mg kg ( 1 ) day ( 1 ) , s . c . ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Phylogenetic relationships among Opisthobranchia ( Mollusca : Gastropoda ) based on mitochondrial cox 1 , trnV , and rrnL genes . ^^^ We reconstructed the phylogenetic relationships among 37 species representing seven main lineages within Opisthobranchia ( Mollusca : Gastropoda ) based on a mitochondrial fragment that included partial cox 1 , complete trnV , and partial rrnL genes ( about 2500 bp ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Moreover , IDM decreased the frequency of exocytotic events stimulated by ionomycin , suggesting that COX 1 activity is stimulated by an increase in intracellular Ca ( 2+ ) concentration ( [ Ca ( 2+ ) ] ( 1 ) ) . ^^^ In conclusion , in ACh stimulated antral mucous cells , an increase in [ Ca ( 2+ ) ] ( 1 ) activates Ca ( 2+ ) regulated exocytotic events and PGE ( 2 ) release mediated by COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ These observations strongly suggested that AT might reduce the I / R induced liver injury by increasing the production of PGI 2 and PGE 2 through activation of COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The two COX ( cyclo oxygenase ) isoenzymes COX 1 and 2 catalyse the initial step in the conversion of arachidonic acid into PG ( prostaglandin ) hormones . ^^^ The identification of an mRNA transcript encoding a splice variant of human COX 1 was reported more than a decade ago [ Diaz , Reginato and Jimenez ( 1992 ) J . ^^^ The splice variant lacks amino acids 396 432 , corresponding to the last 37 amino acids of exon 9 of the gene encoding COX 1 . ^^^ We expressed the full length and spliced COX 1 cDNAs in COS 7 and Sf 9 insect cells , and determined the PG forming activity using incubations with radiolabelled arachidonic acid and HPLC analyses . ^^^ When expressed in either system , abundant PG formation was observed with the full length COX 1 , whereas the spliced protein did not form any detectable product . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , the selective COX 1 inhibitor SC 560 was inactive in this respect . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ There have been some recently well publicized investigations of COX 1 and 2 enzyme variants that may assist in our eventual conceptual understanding of the mechanisms of action of acetaminophen . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX 1 inhibitors . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 expression was higher in intestinal type cancers than diffuse ones . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Humans have two isoforms of Prostaglandin H Synthase or cyclooxygenase : COX 1 and COX 2 . ^^^ COX 1 is cytoprotective . ^^^ 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 P20674	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 P20674	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 . ^^^ The up regulation of COX 1 in the skin was observed 3 and 6 h after carrageenan and was not suppressed in the rats treated with N monomethyl L arginine acetate . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Xanthine plus xanthine oxidase suppressed the COX 1 and 2 activities in a xanthine oxidase concentration dependent fashion . ^^^ NOC 7 activated the COX 1 activity but inhibited the COX 2 activity at concentrations ranging from 1 to 50 microM . ^^^ ONOO ( ) , a product of NO * and O ( 2 ) * , both activated and inhibited the COX 1 and 2 activities , depending on ONOO ( ) concentration . ^^^ 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 ) . ^^^ These results suggest that H ( 2 ) O ( 2 ) , NO * and ONOO ( ) can have different modulatory effects on the COX 1 and 2 activities . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We found low expression of COX 1 at similar intensities for each pair of cell lines . 5 LOX was detected in all cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In unstimulated blood , the plasma levels of thromboxane B 2 ( COX 1 activity ) were 2 to 3 ng / mL , and after calcium ionophore stimulation , large amounts of thromboxane B 2 were produced ( 112 + / 31 ng / mL ) . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Thus we examined IL 1beta stimulated mPGES 1 and cPGES mRNA and protein expression in gastric fibroblasts by quantitative PCR and Western blot analysis , respectively , and studied both their relationship to COX 1 and 2 and their roles in PGE 2 and VEGF production in vitro . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , piroxicam , an unspecific COX inhibitor which displays an increased selectivity towards COX 1 , only prevented secondary hyperalgesia to formalin at a high dose following spinal administration . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ After incubation with bovine pulmonary artery endothelial cells ( BPAEC ) , COX 1 was inhibited stereoselectively by S ketoprofen acylglucuronide , and more significantly by CoA thioester . ^^^ After washing out the medium , COX 1 activity was essentially recovered , indicating a reversible inhibition . ^^^ Using an anti ketoprofen antibody , COX immunoprecipitated from cells exhibited adduct formation for COX 2 but not for COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Previous studies suggest that antagonists of cyclooxygenases 1 and 2 ( COX 1 , 2 ) inhibit angiogenesis in tumor xenografts , but the molecular mechanisms involved remain unclear . ^^^ 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 P20674	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 . ^^^ The shunting hypothesis proposes that inhibition of COX 1 shunts AA metabolism away from production of protective prostanoids and towards cysteinyl leukotriene ( cys LT ) biosynthesis , resulting in bronchoconstriction and increased mucus production . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Western blot analysis confirmed the expression of COX 1 , 2 and PGIS which were expressed by luminal epithelia and smooth muscle cells . ^^^
Interacting proteins: P00395 and P20674	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 inhibits COX 1 in a competitive fashion only at very high concentrations ( IC ( 50 ) = 150 microM ) . ^^^ 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 ) . ^^^ In these same animals , COX 1 was spared at doses greater than 200 mg / kg . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Weak , but mostly consistent immunostaining of the COX 1 enzyme was found in the cochlear structures . ^^^ The COX 1 enzyme seems to be constitutively expressed in the cochlea in contrast to COX 2 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Prostaglandin mediated control of rat brain kynurenic acid synthesis opposite actions by COX 1 and COX 2 isoforms . ^^^ The non selective COX inhibitor diclofenac ( 50 mg / kg , i . p . ) or indomethacin ( 50 mg / kg , i . p . ) , a non selective inhibitor with a preferential selectivity for COX 1 , produced an elevation in brain KYNA . ^^^ It is proposed that increased brain KYNA formation induced by NSAIDs displaying an inhibitory action on COX 1 contribute to their analgesic efficacy as well as to their psychiatric side effects . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ However , COX 1 expression was not different at every time after reperfusion . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Whole stomach perfusion studies demonstrated diminished net alkali secretion in COX 1 ( / ) mice , and application of SC 560 or rofecoxib to wild type mice and mutant mice confirmed that only COX 1 inhibition reduced alkali secretion . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Viral DNA replication was marginally reduced in the presence of a COX 1 / 2 inhibitor , but there was no defect in viral DNA cleavage . ^^^ Electron microscopy analysis revealed an increased number of unusual empty capsid structures in the nuclei of cells infected with PRV in the presence of a COX 1 / 2 inhibitor . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Synergistic effects of Cox 1 and 2 inhibition on bladder and prostate cancer in vitro . ^^^ RESULTS : Significant synergism of Cox 1 and Cox 2 inhibitors was observed in both bladder cancer lines at both 24 and 72 hours . ^^^ Synergism of Cox 1 and 2 inhibitors also was noted in the DU 145 cells at 72 hours , LnCap cells at 24 hours , and PC 3 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 P20674	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 . ^^^ SC 560 [ 5 ( 4 clorophenyl ) 1 ( 4 metoxyphenyl ) 3 trifluoromethylpirazole ] ( COX 1 inhibitor ) did not modify the response to ACh in both groups . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Sinusoidal endothelial COX 1 derived prostanoids modulate the hepatic vascular tone of cirrhotic rat livers . ^^^ COX 1 expression was analyzed and quantified in hepatocytes , Kupffer cells , sinusoidal endothelial cells ( SEC ) , and hepatic stellate cells ( HSC ) isolated from control and cirrhotic rat livers by double immunofluorescence staining , with specific markers for each population using flow cytometry or Western blot analysis . ^^^ 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 ) . ^^^ Cirrhotic livers showed an increased expression of COX 1 in SEC and reduced expression in HSC compared with control livers , whereas COX 1 was similarly distributed in Kupffer cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The magnitude of COX 1 mRNA expression was not altered in each group . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Given the importance of dorsal root ganglia ( DRG ) in pain transmission we examined the expression patterns of COX 1 , 2 and the recently described variant of COX 1 retaining intron 1 , originally referred to as `` COX 3 ' ' but hereafter referred to as COX 1 variant ( COX 1v ) , in mouse L 4 or L 5 DRG taken from normal and COX isozyme deficient mice . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Thus , although they are assumed to result from an axon reflex in primary afferent fibers and neurogenic inflammation , these results suggest that the early anodal current induced vasodilatation is mainly dependent on COX 1 induced PG synthesis . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Consistent with COX 1 increased activity , brain expression of COX 1 protein and mRNA also was increased . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Our data show COX 1 / 2 participates in the inflammatory tissue response to IR injury and its inhibition is associated with an improvement in renal function . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In addition , both drugs significantly reduced PGE 2 levels ( P < 0 . 05 ) 6 h following LPS injection , whereas the probable COX 1 prostanoid TXB 2 was significantly reduced by phenylbutazone ( P < 0 . 05 ) , but not etodolac . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 mRNA was constitutively expressed in the intact cecum , and its expression level was not altered after the mechanical stimulus . ^^^ Mofezolac , a specific COX 1 inhibitor , had no effect on peritoneal adhesion at 30 mg / kg and had only marginal effects on prostaglandin ( PG ) E 2 levels in the cecum or peritoneal fluid . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
As judged from the quaternary structure of bovine COX , the most profound adaptive substitutions are two contiguous cysteines absent in approximately 99 . 9 % of databased COX 1 sequences from Eukaryota , Archaea , and Bacteria . ^^^ This motif lies directly at the docking point of COX 1 helix 3 and cytochrome c , and modeling of bovine COX 1 suggests the possibility of an unprecedented helix terminating disulfide bridge that could alter COX / cytochrome c dissociation kinetics . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Inhibition of COX 1 is likely to account for most of the side effects of NSAIDs ( gastrointestinal irritation , renotoxicity and inhibition of blood clotting ) but a minor contribution also to some of the therapeutic effects ( analgesic and anti inflammatory actions ) can not be excluded . ^^^ 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 P20674	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 . ^^^ In contrast , 15d PG J 2 did not affect the COX 1 expression . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In addition , the expression of Cox 1 was also evaluated . ^^^ 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 . ^^^ In contrast , Cox 1 was positive in 42 . 7 % of primary tumor , 84 . 0 % of lymph node metastases , 37 . 5 % hepatic metastases , and was associated with only tumor size . ^^^ Cox 1 status had no statistically effect on patient survival time . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Permanent inactivation of platelet COX 1 by low dose aspirin might restore anti tumor reactivity . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The selective COX 1 inhibitor , SC 560 ( 100 300 microg kg ( 1 ) i . v . ) , or a would be selective COX 3 inhibitor paracetamol ( acetaminophen , 1 3 mg kg ( 1 ) ) , both agents induced a transient thrombolysis and slightly potentiated thrombolysis by ACE Is . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS : We examined : ( 1 ) the effects of indomethacin ( nonselective NSAID ) , celecoxib and NS 398 ( cyclooxygenase [ COX ] 2 selective NSAIDs ) , SC 560 ( a COX 1 selective NSAID ) , and SC 560 plus celecoxib on survivin expression and extent of injury in rat gastric mucosa ; ( 2 ) the effects of indomethacin , NS 398 , SC 560 , and SC 560 plus NS 398 on survivin expression and injury in gastric epithelial ( RGM 1 ) cells ; and ( 3 ) the effects of survivin suppression with small interfering RNA ( siRNA ) on RGM 1 cell integrity at baseline and following indomethacin injury . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 induction was not observed after CD 44 ligation . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Interestingly , the most antitumor active compounds were potent COX inhibitors ( COX 1 and COX 2 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Moreover , o cresol ( 0 . 5 and 1 mM ) inhibited the COX 1 activity by 40 95 % . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ Light microscopical analysis revealed a homogenous distribution of COX 1 within nearly all cell types of the organ of Corti , but no COX 1 expression in the cuticular plates of pillar cells . ^^^ Both COX 1 and COX 2 immunoreactions were also found in the spiral ganglion . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
All extracts were found to be only weak direct inhibitors of COX 1 ( IC 50 > 400 microg / mL ) . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
By contrast , we found that LAE ( 0 . 02 microg / ml ) selectively inhibited prostaglandin E 2 production by cyclooxygenase ( COX ) 2 , but not COX 1 , which is a plausible mechanism for the analgesic effect . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Twelve young ( Y : 23 + / 1 years ) and 10 older ( O : 69 + / 1 years ) subjects underwent infusions of 137 . 5 mum ACh at four intradermal microdialysis sites : control ( C , Ringer solution ) , NO synthase inhibited ( NOS 1 , 10 mm l NAME ) , cyclooxygenase inhibited ( COX 1 , 10 mm ketorolac ) and NOS 1 + COX 1 . ^^^ Baseline % CVC ( max ) was increased in the O at COX 1 sites ( COX 1 16 + / 1 , NOS 1 + COX 1 16 + / 2 versus C 10 + / 1 % CVC ( max ) ; P < 0 . 001 ) but not in the young , suggesting an age related shift toward COX vasoconstrictors contributing to basal cutaneous vasomotor tone . ^^^ COX 1 and NOS 1 + COX 1 attenuated the peak CVC response to ACh in both groups ( COX 1 O : 29 + / 3 , Y : 22 + / 2 % CVC ( max ) versus C ; P < 0 . 001 both groups ; NOS 1 + COX 1 O : 32 + / 3 versus Y : 29 + / 2 % CVC ( max ) ; versus C ; P < 0 . 001 both groups ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
NO production , but not COX 1 inhibition , may be involved in this effect of indomethacin . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ These studies demonstrate that autocrine regulation of TNF alpha secretion in response to LPS is greatly facilitated by a COX 1 mediated rapid accumulation of PGs as well by a correspondence between the PGs produced and the receptors expressed by the cells . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Selective inhibitors of COX 1 and 2 ( SC 560 and NS 398 respectively ) reduced basal prostacyclin release , and eliminated increased production in response to progestogens . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The expression of its isoforms , COX 1 and 2 is found in many human malignancies . ^^^ 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 . ^^^ Western blot analysis of COX 1 and 2 was performed on four human oral SCC cell lines , all of which showed expression . ^^^ The LIs for COX 1 and 2 were higher for the dysplasias than the SCCs . ^^^ LIs of COX 2 but not COX 1 correlated with the histological grade of dysplasia , being highest for the severe dysplasias ( p < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This paradoxical finding may have resulted , in part , from mechanically induced COX 1 activity . ^^^ In a separate group of animals , the expression of the remaining COX isozyme , COX 1 , was assessed using real time RT PCR 4 h after one bout of 120 loading cycles . ^^^ 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 . ^^^ There were no differences in COX 1 expression in nonloaded ulnas . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Tissue sections were immunostained for COX 1 and COX 2 . ^^^ COX 1 expression was unaltered . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ However , there were no differences in COX 1 expression after reperfusion . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Signal transduction underlying carbachol induced PGE 2 generation and cox 1 mRNA expression of rat brain . ^^^ In this paper we have determined the different signal pathways involved in M ( 1 ) and M ( 3 ) muscarinic acetylcholine receptor ( mAChR ) dependent stimulation of cyclo oxygenase 1 ( cox 1 ) mRNA gene expression and PGE ( 2 ) production on rat cerebral frontal cortex . ^^^ 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 . ^^^ These results suggest that carbachol activation of M ( 1 ) and M ( 3 ) mAChR increased PGE ( 2 ) release associated with an increased expression of cox 1 and NO cGMP production . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We found beta lapachone decreased the levels of cyclooxygenase ( COX ) 2 mRNA and protein expression without significant changes in the levels of COX 1 , which was correlated with a decrease in prostaglandin E 2 ( PGE 2 ) synthesis . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
METHODS : The expression of COX 1 and 2 proteins and mRNAs were determined by western and northern blotting , respectively . ^^^ 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 P20674	Pubmed	SVM Score :0.0
One of the sequenced products was identified as subunit 1 of cytochrome c oxidase ( COX 1 ) , an enzyme which is central to energy metabolism and particularly relevant for developing nervous systems . ^^^ These data not only show that the developing ciliary margin of the chick retina has high energy requirements , but also indicate that COX 1 could play essential roles in developing cells and in stem cells of the eye periphery . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Moreover , the rapid recovery of platelet COX 1 activity and function supports the occurrence of a pharmacodynamic interaction between naproxen and aspirin . ^^^ CONCLUSIONS : Naproxen interfered with the inhibitory effect of aspirin on platelet COX 1 activity and function . ^^^ This pharmacodynamic interaction might undermine the sustained inhibition of platelet COX 1 that is necessary for aspirin ' s cardioprotective effects . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
The P2Y2 R mediated PGE 2 release in the IMCD of hydrated rats was mediated largely by cyclooxygenase ( COX ) 1 as COX 1 specific inhibitor valeroyl salicylate completely blocked the release . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Transcript levels of cyclooxygenase 1 ( COX 1 ) and prostaglandin 12 synthase , however , were unaffected by the stimulation with rhAPC or thrombin . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Portal hypertension ( PHT ) is associated with increased susceptibility of the gastric mucosa to injury by a variety of factors , including nonsteroidal anti inflammatory drugs ( NSAIDs ) that nonselectively inhibit both isoforms of cyclooxygenase ( COX 1 and 2 ) . ^^^ SC 560 , a selective COX 1 inhibitor , did not cause gastric damage in SO rats but dose dependently caused gastric damage in PHT rats . ^^^ 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 P20674	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 P20674	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 . ^^^ These results suggest that COX 1 plays an important role in spinal cord pain processing and sensitization after surgery and that preoperative intrathecal administration of specific COX 1 inhibitors may be useful to treat postoperative pain . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Furthermore , the activity of purified COX 1 was directly inhibited by addition of GSH in a dose dependent manner . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Surprisingly , COX 1 inhibition with SC 560 completely prevented the elevation of PGE 2 seen after irradiation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Basal cells , but not principal cells , and other cells in the epididymis express TRPC 3 and COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ Notably , improved wound healing was characterized by a marked increase in PGE2 / PGD2 biosynthesis that colocalized with induced COX 1 in new tissue at the margin of the wound . ^^^ 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 . ^^^ These data constitute strong evidence that a dysregulation of COX 1 coupled prostaglandin contributes to diabetes impaired wound healing . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Prostacyclin ( PGI ( 2 ) ) is the major prostaglandin generated downstream of COX 1 in these cells , and SC 560 , a COX 1 selective inhibitor , dramatically inhibits PGI ( 2 ) production . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
However , the enhanced vasoconstrictor response to AA in diabetic rats was unaffected by tempol treatment but abolished by inhibition of COX 1 with SC 58560 [ 5 ( 4 chlorophenyl ) 1 ( 4 methoxyphenyl ) 3 ( trifluoromethyl ) 1H pyrazole ] . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Interleukin ( IL ) 1beta , prostaglandin ( PG ) E 2 and PGD 2 levels in colon mucosa and the immunohistochemical expression of COX 1 and 2 were also studied . ^^^ Indeed , treatment with rofecoxib diminished the lost of COX 1 caused by DSS in the crypt epithelium whereas expression of COX 2 remained unaffected . ^^^ CONCLUSIONS : Rofecoxib is protective in acute DSS induced colitis , probably by reducing neutrophil infiltration , inhibiting up regulation of IL 1beta and returning to normal COX 1 expression in the inflamed colonic mucosa . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
None of the PG metabolites tested showed significant effects on the level of COX 1 or cPLA 2 protein expression , except for PGF2alpha , which increased IL 1beta induced cPLA 2 protein expression slightly . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ These assays were used to test 10 to 12 concentrations of a COX 1 selective drug ( SC 560 ) and of 2 NSAIDs currently used in feline practice , meloxicam and carprofen . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The mitochondrial DNA encoded Cox 1 protein , but not nuclear encoded proteins , was down regulated in chloramphenicol treated cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Under normal circumstances , the constitutive isoforms of these enzymes ( constitutive NOS and COX 1 ) are found in virtually all organs . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
BACKGROUND : Cyclooxygenase 1 ( Cox 1 ) plays a key role in arachidonic acid metabolism and in the pathophysiology and immunology of nasal polyposis in patients suffering from aspirin intolerance . ^^^ 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 P20674	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 . ^^^ Sanggenons C , E , and O , that were tested the first time for an inhibitory effect on COX 1 and 2 , showed IC 50 values of 10 14 microM , and 40 50 microM , respectively . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Furthermore , experiments showed that treatment with DEC results in a reduction in the amount of COX 1 protein in peritoneal exudate cells . ^^^ CONCLUSION : These results confirm the important role of the arachidonic acid metabolic pathway in DEC ' s mechanism of action in vivo and show that in addition to its effects on the 5 lipoxygenase pathway , it targets the cyclooxygenase pathway and COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 ) . ^^^ Here , we verify that inhibition of COX 1 results in zebrafish gastrulation arrest and shows that COX 1 expression becomes restricted to the posterior mesoderm during somitogenesis and to posterior mesoderm organs at pharyngula stage . ^^^ Inhibition of COX 1 signaling after gastrulation results in defective vascular tube formation and shortened intersomitic vessels in the posterior body region . ^^^ Functional knockdown of COX 1 using antisense morpholino oligonucleotide translation interference also results in posterior vessel defect in addition to enlarged posterior nephric duct , phenocopying the defects caused by inhibition of COX 1 activity . ^^^ Together , we provide the first evidence that COX 1 signaling is required for development of posterior mesoderm organs , specifically in the vascular tube formation and posterior nephric duct development . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
This effect was also seen with the partially selective COX 1 inhibitor indomethacin ( p < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The effects of MK 801 ( 0 . 1 mg / kg intravenously ) , an NMDA ( N methyl D aspartate ) glutamatergic receptor antagonist , on bladder activity , and on COX 1 and 2 mRNA expression following MCAO were examined . ^^^ COX 1 expression was not influenced by MCAO . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
MAIN OUTCOME MEASURE ( S ) : Prostacyclin production was measured by enzyme immunoassay , the mRNA expression of COX 1 was measured by quantitative real time polymerase chain reaction , and the protein levels of COX 1 and 2 were measured by immunoblotting . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
In this study , we found increased expression of COX 1 mRNA and protein in three out of 10 ovarian cancer cell lines . ^^^ 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 . ^^^ These findings suggest that COX 1 might be a major enzyme regulating PGE 2 production in ovarian cancer cells . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
To study the ability of mitochondrial biogenesis in human granulosa cells , we determined the mitochondrial marker proteins , including the nuclear encoded NADH ubiquinone oxidoreductase alpha subunit 9 ( NDUFA 9 ) and mitochondrial encoded COX 1 , after treatment of the cells with the calcium ionophore A 23187 . ^^^ Treatment of granulosa cells with 0 . 5 microM of A 23187 for 120 h increased the levels of NDUFA 9 and COX 1 subunit by up to 2 . 6 and 2 . 4 fold , respectively . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
A serious side effect of COX 1 and COX 2 inhibitors is renal damage . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
RESULTS : Placental COX 1 RNA decreased with advancing gestational age at delivery ( R ( 2 ) = 0 . 13 , P = . 001 ) , and increased by 43 % when chorioamnionitis was present ( P = . 006 ) . ^^^ Among patients presenting at term , oxytocin use was associated with 30 % lower expression of COX 1 ( P = . 01 ) . ^^^ CONCLUSION : Placental COX 1 RNA at delivery decreases with advancing gestational age and with oxytocin use at term . ^^^ Thus , expression of placental COX 1 is not constitutive . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The selective COX 1 inhibitor SC 560 also does not cause damage , despite evoking a decrease in the PGE 2 level . ^^^ 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 P20674	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 P20674	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 P20674	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 . ^^^ As a consequence , the present work suggests these substances as a new class of potential anti inflammatory agents without the classical side effects due to COX 1 inhibition . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The proximal points of sequence rearrangements are located 3 bp upstream from the COX 1 and 1139 bp upstream from the COX 3 initiation codons . ^^^ The 5 ' termini of both COX 1 and COX 3 mRNAs have been mapped in this common sequence confining the promoter region for the Oenothera mitochondrial COX 1 and COX 3 genes to the homologous sequence block . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
This enzyme has a major role in mediating the inflammatory response , while synthesis of prostaglandins required for normal physiological functioning of the stomach and kidneys is under the control of the constitutive isoform , COX 1 . ^^^ Other NSAIDs in clinical use show varying degrees of selectivity towards COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ Significant COX 1 staining was also detected in both tumor and host osteoblasts . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In continuation of our studies on the mode of action of cobalt alkyne complexes we studied the influence of the compounds on the formation of 12 HHT ( COX 1 product ) and 12 HETE ( 12 LOX product ) by human platelets as an indication of the interference in the eicosanoid metabolism , which is discussed as a target system of cytostatics . ^^^ Co ASS was an efficient COX 1 inhibitor without LOX inhibitory activity and auranofin inhibited both COX 1 and 12 LOX eicosanoid production . ^^^ The missing activity of the fructopyranose complexes at the 12 LOX and the only moderate effects at COX 1 indicate that COX / LOX inhibition may be in part responsible for the pharmacological effects of auranofin and Co ASS but not for those of the fructopyranose complexes . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The target of the primers was also of crucial importance : for the detection of P . falciparum , the most efficient assays amplified either the gene SSUrRNA , or Pf155 / RESA , or Cox 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Zymosan exposure induced a 5 fold increase in cyclooxygenase ( COX ) 2 but not COX 1 protein levels in AMs . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ On the other hand , COX 1 selective oxicam inhibitors gain extra stabilization energy with the change of residue 523 from valine to isoleucine because of the formations of new hydrogen bonds in the enzyme inhibitor complexes . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Our method can be used to search for preventive agents against allergies involving NO , COX 1 , 2 and PGI ( 2 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ It also suggests that no product of the COX 1 gene , including the splice variant COX 1b ( COX 3 ) , is essential for these responses . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX5A subcomplex , three COX 1 containing subcomplexes , a COX4 . ^^^ COX5A subcomplex indicates that association of these nucleus encoded subunits probably precedes their addition to COX 1 during the assembly process . ^^^ COX5A subcomplex , three COX 1 containing subcomplexes , a COX4 . ^^^ COX5A subcomplex indicates that association of these nucleus encoded subunits probably precedes their addition to COX 1 during the assembly process . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Most recently , a splice variant of COX 1 mRNA , retaining intron 1 , and given the names COX 3 , COX 1b or COX 1v , has been described . ^^^ 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 P20674	Pubmed	SVM Score :0.0
PDX concentration appeared not to have effect on the expression levels of COX 1 . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Immunohistochemistry revealed that COX 1 and COX 2 proteins are increased in spinal motor neurons . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Therefore , these results suggest that SAG possesses anti inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX 1 / COX 2 inhibition . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ In summary , our results indicate that the intron 1 retaining Cox 1 splice variant RNA molecules are expressed by human intestinal epithelial cells in a controlled manner , are most likely not translated and play a regulatory role in the cyclooxygenase mediated epithelial osmoregulation . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
NFD 37 compound exhibited a preferred inhibition on enzyme activity of cyclooxygenase ( COX ) 2 over COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX variant proteins may act in roles which diverge from those of COX 1 and 2 . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ COX 1 immunostaining was at a basal level in zygotes and a low level at the 2 cell stage , reaching a high level from the 4 cell to blastocyst stage . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In this study , we first confirmed the existence of intron 1 retained COX 1 in certain human tissues at both the mRNA and protein levels . ^^^ Molecular biology studies revealed that three distinct COX 1 splicing variants exist in human tissues . ^^^ Accordingly , we conclude that intron 1 retained human COX 1 is not likely to be the therapeutic target of acetaminophen or a candidate of COX 3 . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
DHA and eicosapentaenoic acid slightly enhanced IL 1beta induced cyclooxygenase ( COX ) 2 , but not COX 1 , expression , whereas arachidonic acid had no effect . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , the expression of COX 1 , mPGES 1 and 2 was similar between intestinal metaplasia and gastric metaplasia . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
LPS up regulated mRNA expression of inducible nitric oxide synthase , cyclooxygenase ( COX ) 2 , interleukin 6 , and toll like receptor 2 , 4 , and 9 was also markedly attenuated without affecting the expression levels of several constitutive genes , including COX 1 , as detected by reverse transcription polymerase chain reactions . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ These increases were accompanied by normalized cardiac ER alpha and ER beta protein levels , PGC 1 , and COX 1 mRNA expression , mitochondrial COX activity , and ATP contents . ^^^ The flutamide mediated restoration of cardiac function , the increases in aromatase activity and estrogen levels , ER alpha , ER beta , PGC 1 , COX 1 , COX activity , and ATP contents were , however , abolished when ER antagonist ICI 182 , 780 was administrated along with flutamide . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
NCX 4016 in vivo undergoes metabolism into deacetylated and / or denitrated metabolites , and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX 1 , or whether it can block it as a whole molecule . ^^^ 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 . ^^^ In conclusion , our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX 1 and that the presence of a spacer and NO donating moiety in the molecule slows the kinetics of COX 1 inhibition by NCX 4016 , compared with aspirin . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Despite clear benefit from aspirin in patients with cardiovascular disease ( CAD ) , evidence of heterogeneity in the way individuals respond has given rise to the concept of ' aspirin resistance . ' AIMS : To evaluate the hypothesis that incomplete suppression of platelet COX as a consequence of variation in the COX 1 gene may affect aspirin response and thus contribute to aspirin resistance . ^^^ Patients were genotyped for five single nucleotide polymorphisms in COX 1 [ A 842G , C22T ( R8W ) , G128A ( Q41Q ) , C644A ( G213G ) and C714A ( L237M ) ] . ^^^ RESULTS : COX 1 haplotype was significantly associated with aspirin response determined by AA induced platelet aggregation ( P = 0 . 004 ; 4 d . f . ) . ^^^ CONCLUSION : Genetic variability in COX 1 appears to modulate both AA induced platelet aggregation and thromboxane generation . ^^^ Heterogeneity in the way patients respond to aspirin may in part reflect variation in COX 1 genotype . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
This report compares two CINODs , NMI 1182 ( naproxen glyceryl dinitrate ) and AZD 3582 ( naproxen n butyl nitrate ) , for their ability to inhibit COX 1 and 2 , deliver bioavailable nitric oxide , and release naproxen , using in vitro biochemical and pharmacological methods . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 ) . ^^^ We conclude that endogenous PGs derived from COX 1 are involved in the mucosal defense of the esophagus and that PGE 2 has a biphasic influence on esophageal injury , depending on the dose : a protective effect at low doses and a deleterious effect at high doses , both mediated by EP 1 receptors the latter effect of PGE 2 may be brought about by stimulation of the pepsin secretion . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Aspirin is effective in the therapy of cardiovascular diseases , because it causes acetylation of cyclooxygenase 1 ( COX 1 ) leading to irreversible inhibition of platelets . ^^^ Although shedding occurred normally in COX 1 deficient murine platelets , shedding was completely blocked by a broad range metalloproteinase inhibitor and , more importantly , in mouse platelets expressing an inactive form of ADAM 17 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Expression of cyclooxygenase ( COX ) 2 , but not COX 1 , in the renal medulla is stimulated by chronic salt loading ; yet the functional implication of this phenomenon is incompletely understood . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
PGE 2 in EBC is primarily derived from COX 1 activity , and COX inhibition may redirect arachidonic acid metabolism towards the 5 lipoxygenase pathway . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Coupling of COX 1 to mPGES 1 for prostaglandin E 2 biosynthesis in the murine mammary gland . ^^^ 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 ) . ^^^ We demonstrate that expression of COX 1 , generally considered constitutive , increases dramatically with lactogenic differentiation of the murine mammary gland . ^^^ PGE 2 production is dependent on COX 1 , as PGE 2 levels are nearly undetectable in COX 1 deficient mammary glands . ^^^ Interestingly , PGE 2 levels are similarly reduced in lactating glands of mPGES 1 deficient mice , indicating that PGE 2 biosynthesis results from the coordinated activity of COX 1 and mPGES 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The isoform COX 1 , instead , steadily expressed in tissues , would be responsible of continuous prostaglandin synthesis maintaining patent the ductus arteriosus in uterus . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Thromboxane B 2 ( TxB 2 ) was assayed as a measure of COX 1 activity in clotted blood . ^^^ 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 . ^^^ RESULTS : Ketoprofen , aspirin , and etodolac were COX 1 selective . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Here , we describe a fast efficient method for the direct incorporation of cyclooxygenase 1 and 2 ( COX 1 and 2 ) isozymes into liposomes without loss of activity . ^^^ Purified COX 1 and 2 spontaneously incorporate into large unilamellar vesicles produced from a mixture of DOPC : DOPS ( 7 : 3 ) that has been doped with oleic acid . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX 1 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Tumor initiation inhibition through inhibition COX 1 activity of a traditional Korean herbal prescription , Geiji Bokryung Hwan , in human hepatocarcinoma cells . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The effects of different COX and NOS inhibitors on the intestinal motor activity were tested . mRNA expression of COX 1 was not modified by inflammation , whereas mRNA expression of neuronal NOS was reduced in all indomethacin treated rats . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
No effect on COX 1 gene expression was observed . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Unlike traditional non steroidal anti inflammatory drugs ( NSAIDs ) most coxibs do not significantly inhibit COX 1 and are therefore less toxic to the gastrointestinal tract . ^^^ First , selective inhibition of COX 1 lowers platelet synthesis of thromboxane ( TXA ( 2 ) ) , a thrombogenic and atherogenic eicosanoid . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Double immunofluorescence was performed using antibodies against mPGES 1 , COX 1 , COX 2 , and CD 163 . ^^^ The number of COX 1 expressing cells in synovial tissue was also significantly decreased by glucocorticoid treatment . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
When comparing COX isoforms ( COX 1 and COX 2 ) , the authors found that overlapping and mutually exclusively properties coexist . ^^^ COX 2i originally were developed to minimize interference with the gastroprotective properties of the COX 1 isoform , while selectively preventing prostanoid synthesis expressed solely at sites of bodily trauma or other inflammation . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
The expression of COX 1 was notably lower than that of control group after CHCS treating ( 632 . 8 + / 40 . 6 vs 895 . 1 + / 44 . 2 , P < 0 . 05 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ From these findings the initial concept that only inhibition of COX 1 interferes with gastrointestinal defense has to be re evaluated . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
These drugs have a broad range of relative selectivity towards the COX family , mainly towards two isoforms of these enzymes : COX 1 and 2 . ^^^ As examples , ketorolac , flurbiprofen , ketoprofen and indomethacin have increased COX 1 selectivity when compared with naproxen and ibuprofen . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenases ( COX 1 and COX 2 ) catalyze the conversion of arachidonic acid to prostaglandins ( PGs ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The binding of the CD 14 IgG chimera to HuPrP 82 146 or amyloid beta 1 42 damaged neurons was reduced by pre treatment with cyclo oxygenase ( COX ) 1 inhibitors and in co cultures , COX 1 inhibitors significantly increased neuronal survival . ^^^ These results indicate that prostaglandin D 2 , produced following activation of COX 1 by sub lethal concentrations of HuPrP 82 146 or amyloid beta 1 42 , causes phenotypic changes in neurons that activates microglial cells and leads to neuronal loss . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX deficiency has been associated with mitochondrial DNA mutations in COX 1 , 2 , and 3 with large scale deletions of the mitochondrial genome and with point mutations in mitochondrial tRNA genes . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ It was observed that COX 1 mRNA and protein were up regulated in the gastric mucosa of PSD rats . ^^^ However , indomethacin , a COX 1 preferential non selective COX inhibitor , significantly reduced mucosal PGE 2 content and produced more severe mucosal damage in PSD rats than in the controls . ^^^ These results suggest that PSD enhances COX 1 biosynthesis of gastroprotective PGE 2 as an adaptive response of the stomach to stress . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Time course of COX 1 and COX 2 expression during ischemia reperfusion in rat skeletal muscle . ^^^ COX 1 mRNA was expressed in control muscle and was increased at 72 h of reperfusion , but the levels of associated COX 1 protein detected in control and injured gastrocnemius muscle were similar . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Incomplete inhibition of COX 1 seems to be implicated in persistent TxA 2 production . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In vivo evaluation in rats bearing AH109A hepatoma demonstrated minimal specific binding of [ 11C ] to COX 1 in peripheral organs , such as the spleen and small intestine . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase 1 ( COX 1 ) inhibition by a selective inhibitor valeryl salicylate , or nonselective inhibitors at 10 mg / kg , including aspirin , ibuprofen , indomethacin , and picroxicam , attenuated by 29 % 46 % the duration of loss of righting reflex induced by diazepam ( 20 mg / kg ) in mice . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Involvement of COX 1 and up regulated prostaglandin E synthases in phosphatidylserine liposome induced prostaglandin E 2 production by microglia . ^^^ On the other hand , mPGES 2 and cytosolic PGES ( cPGES ) that are functionally coupled with COX 1 were upregulated after treatment with PS liposomes or LPS . ^^^ 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 . ^^^ These observations strongly suggest that the up regulation of terminal PGESs that are preferentially coupled with COX 1 , especially mPGES 2 , plays the pivotal role in PS liposome induced PGE 2 production by microglia . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ Gene disruption or inhibition of COX 1 did not impair ulcer healing . ^^^ 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 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Considering possible tumorigenic activity of cyclooxygenase ( COX ) isozymes in myeloma , we examined expression levels of COX 1 and 2 in seven human myeloma cell lines ( ARH 77 , IM 9 , RPMI 8226 , HPC , HS Sultan , TSPC 1 , and U 266 ) . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity . ^^^ Approximately one third of the variability was attributable to differences between individuals , suggesting the contribution of genetic sources of variance , such as candidate polymorphisms detected in COX 1 and CYP2C9 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
This inhibitory effect of cyclosporin occurred at the posttranscriptional level , as evidenced by normal increases in COX 1 and COX 4 mRNAs in response to exercise in the cyclosporin treated rats . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ The potencies of diclofenac , naproxen , rofecoxib , and salicylate , but not aspirin , celecoxib , indomethacin , lumiracoxib , meloxicam , or SC 560 , against COX 1 ( human platelets ) increased as protein concentrations were reduced . ^^^ 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 P20674	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 P20674	Pubmed	SVM Score :0.0
Increasing evidence suggests that COX 1 may also play a similar role . ^^^ 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 . ^^^ In this study we investigated the expression of COX 1 in non tumor and malignant human liver tissues , as well as the effects of the highly selective COX 1 inhibitor SC 560 on cell growth and apoptosis in human HCC cell lines . ^^^ Expression of COX 1 was detected in nearly all the samples assayed , although with a high variability between non tumoral ( NT ) and malignant tissues . ^^^ The percentage of COX 1 positive cells was significantly higher in the NT tissues than in the tumors ( p < 0 . 0001 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ In concordance , an increase in brain KYNA concentration ( 150 300 % ) , induced by the COX 1 inhibitor indomethacin ( 50 mg / kg , i . v . , 1 h or , i . p . , 3 . 5 h ) , produced opposite effects , that is , increased firing rate and burst firing activity . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
In contrast , HASMCs with or without LPS treatment showed constitutive expression of COX 1 mRNA and protein . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ We conducted this prospective study to analyze the expression , distribution , and cellular localization of COX 1 and 2 and thus to elucidate the role of COX in human kidney transplantation . ^^^ COX 1 and 2 expression was localized in each biopsy by immunohistochemistry . ^^^ We found a highly significant up regulation of COX 1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well preserved tissue . ^^^ This is the first prospective study demonstrating a significant induction of both COX 1 and 2 in human allograft biopsies with acute rejection after renal transplantation . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
With cancer cells , rofecoxib was less effective and two NSAIDS selective for COX 1 were without effect in inhibiting NOX activity . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ These non steroidal anti inflammatory drugs ( NSAIDs ) except for zaltoprofen , strongly inhibited an acetic acid induced writhing response related to PGs based on COX 1 , at lower doses . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This study examines the role played by cyclooxygenase ( COX ) isoforms ( COX 1 and 2 ) in the regulation of colonic neuromuscular function in normal rats and after induction of colitis by 2 , 4 dinitrobenzenesulfonic acid ( DNBS ) . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 expression increased only at 10 days . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Indole and indoline type basic COX 1 selective competitive inhibitors , 5 amino 1 ( 3 , 5 dimethylbenzoyl ) 1H indole ( 1 ) and 5 amino 1 ( 3 , 5 dimethylphenyl ) 2 , 3 dihydro 1H indole ( 2 ) , were found to possess anti angiogenic activity estimated as a tube formation inhibition using human umbilical vein endothelial cells ( HUVECs ) . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In conclusion , both COX 1 and COX 2 selective inhibitors constrict fetal DA . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ The literature indicates that natural product based compounds are mainly COX 1 selective . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Basal myofibroblast COX 1 and COX 2 expression was downregulated in Gi alpha 2 / cells . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Parsimony analysis of mitochondrial DNA sequences ( 12S rDNA and cox 1 genes ) yielded phylogenetic trees with a lower consistency index than for LSU sequences , and with fewer reliably supported clades . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Carbachol and PGE ( 2 ) increase endogenous PGE ( 2 ) production and the COX 1 mRNA levels by activation of PLA ( 2 ) s . ^^^ The COX 1 and COX 2 activity participated in the production of PGE ( 2 ) triggered by exogenous PGE ( 2 ) . ^^^ While in carbachol PGE ( 2 ) only COX 1 activity is affected . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ The latter observation may be related to the higher expression of COX 1 measured in HIEEC . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ COX 1 gene disruption also reduced inflammatory edema and joint destruction in female , but not male mice , although females of both COX / lines did show some bony destruction . ^^^ There was no difference in ipsilateral allodynia between COX 1 knockout and wild type animals , but female COX 1 / mice showed reduced contralateral allodynia compared with male COX 1 / or wild type mice . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ A selective cyclooxygenase ( COX ) 2 inhibitor , NS 398 , completely inhibited the initial phase productions , except for PGD ( 2 ) and thromboxane B ( 2 ) , whose productions were also dependent on COX 1 . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
The major side effect of aspirin is related to its ability to suppress prostaglandin ( PG ) synthesis by constitutive cyclooxygenase 1 ( COX 1 ) . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
These responses were attenuated by COX 1 knock down , which mimics the beneficial effects of low dose aspirin . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 and 2 expressions in sex related organs of neonatally estrogen treated rats and in activated and nonactivated macrophage RAW264 . 7 cells with phytoestrogen . ^^^ 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 P20674	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 P20674	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 . ^^^ COX 1 inhibition had no effect on incidence ( control : 90 % [ 9 : 10 ] versus SC 560 : 89 % [ 8 : 9 ] ) or severity of Ang 2 induced AAA formation . ^^^
Interacting proteins: P00395 and P20674	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 % . ^^^ Western blot analysis indicated a comparable content of COX 1 protein in arterioles of WT and eNOS KO mice . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Synthesis and biological evaluation of linear phenylethynylbenzenesulfonamide regioisomers as cyclooxygenase 1 / 2 ( COX 1 / 2 ) inhibitors . ^^^ 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 ) . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : Il1r1 / Tnfrsf1a double knockout mice had significantly lower rates of preterm delivery than controls ( 8 % vs 69 % with 7 10 10 ( 7 ) bacteria , P = . 002 , and 52 % vs 81 % with 1 . 4 10 10 ( 8 ) bacteria , P = . 003 ) and significantly lower myometrial levels of cyclooxygenase ( COX ) 2 , but not COX 1 mRNA . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 and COX 2 mRNA did not differ between any groups at 5 d . ^^^ At 14 d , however , L NAME caused a 30 fold increase in plantaris COX 1 mRNA expression independent of loading condition . ^^^ 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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ COX 1 disruption had no effect ( 15 . 6+ / 2 . 6 ; n=8 ) . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ There were no changes in messenger RNA ( mRNA ) and protein expression for COX 1 in cyclic pigs . ^^^ However , no upregulation of COX 1 protein was detected . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 . ^^^ The plasma 6 keto PGF1alpha concentration and the expression of COX 1 mRNA in these vessels and the small intestine were closely correlated with such hemodynamic parameters as portal venous inflow ( PVI ) , splanchnic vascular resistance ( SVR ) and free portal venous pressure ( FPP ) ( P < 0 . 05 ) . ^^^ CONCLUSION : The expression of COX 1 mRNA and the levels of PGI 2 were closely related to the hyperdynamic circulatory state of portal hypertensive rats . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
Aspirin resistance in coronary artery disease is correlated to elevated markers for oxidative stress but not to the expression of cyclooxygenase ( COX ) 1 / 2 , a novel COX 1 polymorphism or the PlA ( 1 / 2 ) polymorphism . ^^^ Platelet cyclooxygenase 1 ( COX 1 ) and COX 2 mRNA and protein expression were without significant differences between the two groups . ^^^ DNA sequencing detected a novel platelet COX 1 single nucleotide polymorphism ( SNP ) resulting in amino acid exchange at position 8 ( Arg8 / Trp8 ) . ^^^ 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 . ^^^ However , a correlation exists to elevated eicosanoids generated by oxidative stress indicating COX 1 independent pathways for the generation of platelet activating molecules represent a potential cause for AR . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
However , at a concentration of 10microg / ml , the compound showed weak inhibition of 12 ( S ) HETE production in human platelets and at a concentration of 50microM it produced no inhibition of COX 1 and 2 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
COX 1 is constitutively expressed in many tissues and seems to be involved in the housekeeping function of prostanoids . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Spinal COX 1 expression and activity increase following incisional paw surgery in rats , although the stimulus for this increase is not known . ^^^ In the current study we tested whether spinal dynorphin expression increases after incisional surgery and induces hypersensitivity in this setting , and whether dynorphin stimulates COX 1 activity in spinal cord microglia . ^^^ Paw incision increased COX 1 immunoreactivity in the L 4 L6 ipsilateral spinal cord , and these cells were confirmed to be microglia by co localization with OX 42 . ^^^ Spinal cord microglia in culture expressed COX 1 immunoreactivity and released PGE 2 , but dynorphin A failed to increase release of PGE 2 in these cultures . ^^^ These results suggest that increased COX 1 expression occurs in spinal cord microglia following incisional surgery . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We studied mtDNA complementation in human cells by fusing two cell lines , one containing a homoplasmic mutation in a subunit of respiratory chain complex 4 , COX 1 , and the other a distinct homoplasmic mutation in a subunit of complex 3 , cytochrome b . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ These effects were associated with a significant reduction in the COX 1 / 2 derived prostaglandin E 2 ( PGE 2 ) production . ^^^ These results provide a novel insight into the mechanism by which EGCG , by affecting ET ( A ) R dependent COX 1 / 2 pathways may inhibit ovarian tumors suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which activation of ET ( A ) R by ET 1 plays a critical role in tumor growth and progression . . ^^^
Interacting proteins: P00395 and P20674	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 . ^^^ Human osteoclasts actively produced PG , and the COX 1 pathway was implicated in the control of bone resorption . ^^^ CONCLUSION : These results indicate that PG may be important autacoids for the control of osteoclast biology and that the COX 1 pathway is implicated in the inhibition of bone resorption . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
PGC 1alpha ( peroxisome proliferator activated receptor [ PPARgamma ] coactivator 1alpha ) activates PPARalpha and mitochondrial transcription factor A ( Tfam ) , which regulate proteins , fatty acid and ATP metabolism ( i . e . , FAT / CD36 , MCAD , and COX 1 ) . ^^^ E 2 and DPN treatments attenuated the decrease in cardiac mitochondrial ATP , abrogated the T H induced lipid accumulation , and normalized PGC 1alpha , PPARalpha , FAT / CD36 , MCAD , Tfam , and COX 1 after T H . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
We hypothesized that there would be augmented vasoconstriction to AA , mediated via COX 1 in rats fed a high fat ( HF ) diet for 10 weeks ( from 3 to 13 weeks old ) compared to those fed regular rat chow . ^^^ Inhibitors to AA metabolism suggest that COX 1 activity predominates in rats fed a HF diet . ^^^ 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 . ^^^ These results suggest that vasoconstriction induced by AA is augmented in rats fed the HF diet due to increased COX 1 expression and activity . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	Pubmed	SVM Score :0.0
COX 1 generates cytoprotective prostanoids such as prostaglandin ( PG ) E 2 and prostacyclin ( PGI 2 ) . ^^^ 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 P20674	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 . ^^^ In most cases however , it produced a significant decrease in the inhibitory activity towards COX 1 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
This suggests that COX 1 oxygenates 2 AG , so studies were carried out to identify enzymes involved in zymosan dependent PG G and PG synthesis . ^^^ 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 . ^^^ In contrast , when exogenous substrates were provided to COX 1 / macrophages , PG G but not PG synthesis was reduced . ^^^ These studies confirm that peritoneal macrophages synthesize PG Gs in response to zymosan , but that this process is primarily COX 1 dependent , as is the synthesis of PGs . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
We have recently reported that cyclooxygenase ( COX ) 2 deficiency affects brain upstream and downstream enzymes in the arachidonic acid ( AA ) metabolic pathway to prostaglandin E 2 ( PGE 2 ) , as well as enzyme activity , protein and mRNA levels of the reciprocal isozyme , COX 1 . ^^^ 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 . ^^^ We found that brain PGE 2 concentration was significantly increased , whereas thromboxane B 2 ( TXB 2 ) concentration was decreased in COX 1 ( / ) mice . ^^^ The mechanism of NF kappaB activation in the COX 1 ( / ) mice involved the up regulation of protein expression of the p 50 and p 65 subunits of NF kappaB , as well as the increased protein levels of phosphorylated IkappaBalpha and of phosphorylated IKKalpha / beta . ^^^ 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 . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Renal cortical regulation of COX 1 and functionally related products in early renovascular hypertension ( rat ) . ^^^ 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 . ^^^ COX 1 and related components were studied in two kidney one clip ( 2K1C ) Goldblatt hypertensive rats with combined chronic ANG 2 or bradykinin B ( 2 ) receptor blockade using candesartan ( cand ) or the B ( 2 ) antagonist Hoechst 140 ( Hoe ) . ^^^ By contrast , COX 1 and PGES were uniformly downregulated in both kidneys , along with reduced urinary PGE ( 2 ) levels , and showed no clear relations with the NO status . ^^^ ANG 2 receptor blockade confirmed negative regulation of COX 2 by ANG 2 but blunted the decrease in COX 1 selectively in nonclipped kidneys . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ RESULTS : COX 1 mRNA levels were significantly higher in CF nasal polyps ( median 2 . 34 , 25 75th percentiles 1 . 6 3 . 2 ) than in the nasal mucosa ( 0 . 78 , 0 . 11 1 . 21 ) , while there was no difference with non CF nasal polyps ( 1 . 11 , 0 . 80 3 . 15 ) . ^^^ COX 1 protein levels were significantly higher in CF nasal polyps ( 3 . 63 , 2 . 71 4 . 27 ) than in nasal mucosa ( 1 . 55 , 0 . 66 2 . 33 ) and non CF nasal polyps ( 2 . 19 , 1 . 72 3 . 68 ) . ^^^ 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 P20674	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 . ^^^ In the normal skin of COX 1 deficient mice , skin PGD 2 level was lower than that of wild type mice , although PGE 2 , PGI 2 and PGF ( 2 alpha ) levels were almost equal to those of wild type . ^^^ In the scratched skin of COX 1 deficient mice , PGD 2 , PGE 2 , PGI 2 and PGF ( 2 alpha ) levels were lower than those of wild type mice . ^^^ 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 P20674	Pubmed	SVM Score :0.0
Surprisingly , the `` selective COX 1 ' ' inhibitor SC 560 completely inhibited TNFalpha induced PGE 2 synthesis in neurons at nanomolar concentrations . ^^^ Most importantly , SC 560 blocked TNFalpha induced PGE 2 synthesis in COX 1 deficient spinal cord neurons , demonstrating a COX 1 independent inhibition of PGE 2 synthesis . ^^^ Taken together our data demonstrate that SC 560 acts at least in some cell types as an unselective COX inhibitor despite its selectivity toward COX 1 under cell free conditions . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
One of the `` cyclo oxygenases ' ' , called COX 1 is responsible for making prostaglandins , which among other things , protect the stomach and kidney from damage . ^^^ It is now clear that inhibition of COX 1 accounts for the unwanted side effects of aspirin like drugs such as gastric irritation and renal damage . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation , cyclooxygenase enzymes ( COX 1 and 2 ) and lipid peroxidation inhibitory activities in vitro . ^^^ 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 P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
Cyclooxygenase ( COX ) 2 plays a harmful role in cerebral ischemic / reperfusion injury , but the role of COX 1 is uncertain . ^^^ During the first 15 min of stroke , CBF decreased in the penumbra in both homozygous COX 1 gene knockout and wild type mice . ^^^ Mild poststroke impairment in sensorimotor behavior was detected by the turning in an alley test in which the COX 1 gene knockout mice performed better . ^^^ The relative infarct volume at 72 hr after stroke was 8 . 1 % and 8 . 4 % in the COX 1 gene knockout and wild type mice , respectively . ^^^ Thus , COX 1 gene knockout does not affect the brain ' s susceptibility to photothrombotic stroke . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
METHODS : We studied 30 patients with CHD ( ie , chronic stable angina , unstable angina , and acute myocardial infarction ) and 10 healthy subjects , who were treated with low dose aspirin ( 100 mg daily ) on a long term basis , 12 hours after the administration of 160 mg aspirin to ensure saturation of platelet COX 1 activity . ^^^ In CHD patients we detected enhanced variability in serum TXB 2 generation ( median , 3 . 1 ng / mL [ range , 0 . 15 47 ng / mL ] ; mean , 8 . 5 + / 12 . 3 ng / mL ) , which in 8 patients ( 27 % ) exceeded the mean value + 2 SDs detected in healthy subjects ( ie , 8 . 4 ng / mL ) , set as the limit value for an adequate inhibition of platelet COX 1 by aspirin . ^^^ 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 . ^^^ CONCLUSIONS : Heterogeneity in the suppression of platelet COX 1 activity by aspirin occurred in CHD patients . ^^^ The measurement of the serum TXB 2 level seems to be an appropriate biomarker to identify patients who have an inadequate inhibition of platelet COX 1 activity by aspirin . . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 P20674	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 . ^^^ These data with exploratory behavior and laparotomy agree with studies with reflexive withdrawal responses after incisional surgery and indicate that COX 1 inhibition reduces pain responses after surgery . ^^^ Spinal COX 1 inhibition completely restores exploratory activity , including rearing behavior that stretches the abdominal muscles . ^^^ These data suggest that targeting COX 1 in the spinal cord may produce postoperative analgesia . . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
In conclusion , the expression of iNOS in the small intestine following administration of NSAIDs results from COX 1 inhibition and is functionally associated with intestinal hypermotility and bacterial invasion . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	Pubmed	SVM Score :0.0
RESULTS : The coadministration of placebo or celecoxib did not undermine the aspirin related inhibition of platelet COX 1 activity , as assessed by measurements of serum thromboxane B ( 2 ) ( TXB ( 2 ) ) levels , as well as platelet function . ^^^ 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 P20674	Pubmed	SVM Score :0.0
COX 1 immunohistochemistry was negative in all cases . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
To further examine the contribution of COX derived eicosanoids to basal lung function and to allergic lung inflammation , transgenic ( Tr ) mice were generated in which overexpression of human COX 1 was targeted to airway epithelium . ^^^ Although no differences in basal respiratory or lung mechanical parameters were observed , COX 1 Tr mice had increased bronchoalveolar lavage fluid PGE ( 2 ) content compared with wild type littermates ( 23 . 0 + / 3 . 6 vs 8 . 4 + / 1 . 4 pg / ml ; p < 0 . 05 ) and exhibited decreased airway responsiveness to inhaled methacholine . ^^^ 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 . ^^^ In these mice , the presence of the COX 1 transgene did not alter allergen induced inflammation but significantly attenuated allergen induced airway hyperresponsiveness , coincident with reduced airway leukotriene levels . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
Selective inhibitors of cyclooxygenase ( COX ) 2 were developed to improve the safety of anti inflammatory therapy in patients at elevated risk for gastrointestinal complications which are thought to be caused primarily by depression of COX 1 derived mucosal prostanoids . ^^^
Interacting proteins: P00395 and P20674	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 ) . ^^^ There were 4 , 4 , 22 , 16 , 35 point mutations in COX 1 from 5545 to 6838 bp in 5 shocked rats . ^^^
Interacting proteins: P00395 and P20674	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 P20674	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 P20674	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 . ^^^ COX5A subassembly was not detected in COX 10 deficient cells , which suggests that heme A incorporation into MTCO 1 occurs prior to association of MTCO 1 with COX 4 and COX5A . ^^^
Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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Interacting proteins: P00395 and P20674	Pubmed	SVM Score :0.0
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