Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.53476631 |
The loss of both cytosolic and nuclear soluble 5 LO , with concomitant increase exclusively at the NE , as well as co localization with FLAP , were confirmed by indirect immunofluorescent and confocal microscopy . 0.53476631^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.66722775 |
These results indicate that the nuclear envelope is the site at which 5 LO interacts with FLAP and arachidonic acid to catalyze LT synthesis in activated AM as well as PBL , and that in resting AM the euchromatin region of the nucleus is the predominant source of the translocated enzyme . 0.66722775^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :1.2848163 |
Lipoxygenase ( 5 LO ) and its activating protein ( FLAP ) are both required for cellular leukotriene ( LT ) synthesis , with 5 LO catalyzing both the synthesis of ( 5S ) 5 hydroperoxy 6 , 8 , 11 , 14 eicosatetraenoic acid ( 5 HPETE ) from arachidonic acid and the subsequent synthesis of LTA 4 from 5 HPETE . 1.2848163^^^ These studies in Sf 9 cells , together with our recent demonstration that FLAP specifically binds arachidonic acid , suggests that FLAP activates 5 LO by acting as an arachidonic acid transfer protein . . 0.78186564^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.6630837 |
The aim of this study was to test if human platelet leukotriene C 4 synthase ( LTC 4 S ) is pharmacologically different from cloned and expressed LTC 4 S and , in light of the significant homologies between 5 lipoxygenase activating protein ( FLAP ) and LTC 4 S , if different potencies of leukotriene synthesis inhibitors acting through binding with FLAP ( FLAP inhibitors ) reflect in different potencies as LTC 4 S inhibitors . 0.6630837^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.55148376 |
Using the Spodoptera frugiperda ( Sf 9 ) insect cells , we demonstrate that FLAP causes a large stimulation ( 190 fold ) of the conversion of 12 ( S ) hydroxyeicosatetraenoic acid ( 12 ( S ) HETE ) to 5 , 12 diHETE when co expressed with 5 lipoxygenase . 0.55148376^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.54578353 |
It has been shown that 5 lipoxygenase binds to membrane 5 lipoxygenase activating protein ( FLAP ) to produce 5 ( S ) HETE , and thus FLAP inhibitor suppresses cellular 5 ( S ) HETE production . 4 . 0.54578353^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.55682981 |
The decrease in 5 LO metabolism was associated with reduced FLAP ( 30 . 1 + / 14 . 5 % of control ) and 5 LO expression ( 49 + / 13 . 7 % of control ) . 0.55682981^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We have found overexpression of several genes related to arachidonate mobilization including phospholipase A 2 , group 4 and 5 , phospholipase A 2 activating protein and lysophospholipase 1 and 3 , as well as lipoxygenation like arachidonate 12 lipoxygenase and arachidonate 5 lipoxygenase activating protein . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Arachidonate 5 lipoxygenase activating protein ( ALOX5AP ) gene is involved in the pathogenesis of atherosclerotic cardiovascular disease ( CVD ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Variants of the gene ALOX5AP ( also known as FLAP ) encoding arachidonate 5 lipoxygenase activating protein are known to be associated with risk of myocardial infarction . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The expression of arachidonate 5 lipoxygenase ( arachidonate : oxygen 5 oxidoreductase , EC 1 . 13 . 11 . 34 ) and the 5 lipoxygenase activating protein ( FLAP ) genes in human tonsillar B cells and lymphoblastoid B cell lines was demonstrated at the transcriptional level by reverse transcription PCR analysis . ^^^ Also , five lymphoblastoid T cell lines were investigated and found to express the FLAP gene but not the 5 lipoxygenase gene , suggesting that the transcriptional regulation of these two genes is different . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
MK 0591 has a high affinity for 5 lipoxygenase activating protein ( FLAP ) as evidenced by an IC 50 value of 1 . 6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In a previous study , osteosarcoma cells expressing both 5 lipoxygenase ( 5 LO ) and 5 lipoxygenase activating protein ( FLAP ) synthesized leukotrienes upon A 23187 stimulation ( Dixon , R . ^^^ Osteosarcoma cells expressing 5 LO but not expressing FLAP were unable to synthesize leukotrienes . ^^^ To examine the role of FLAP in A 23187 induced translocation of 5 LO to a membrane fraction , we have studied the A 23187 stimulated translocation of 5 LO in osteosarcoma cells expressing both 5 LO and FLAP , and in osteosarcoma cells expressing 5 LO only . ^^^ We demonstrate that in cells expressing both 5 LO and FLAP , 5 LO translocates to membranes in response to A 23187 stimulation . ^^^ In osteosarcoma cells expressing 5 LO but not expressing FLAP , 5 LO is able to associate with membranes following A 23187 stimulation . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
A binding assay has been developed to measure the affinity of leukotriene synthesis inhibitors for 5 lipoxygenase activating protein ( FLAP ) , using human leukocyte membranes as the source of FLAP and a radioiodinated leukotriene synthesis inhibitor , 125I L 691 , 831 , as ligand . ^^^ In addition , direct 5 lipoxygenase inhibitors and a selection of eicosanoids were unable to compete for FLAP binding . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
It was demonstrated that the 18 kDa protein is necessary for the cellular activation of leukotriene synthesis and was named 5 lipoxygenase activating protein ( FLAP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We demonstrate that differentiation of HL 60 cells with DMSO results in coordinate induction of 5 LO and 5 LO activating protein ( FLAP ) . ^^^ The production of LTB 4 , 5 LO protein , 5 LO mRNa and FLAP RNA increased coordinately . ^^^ However , two approaches demonstrated no increase in the initiation of transcription of 5 LO and FLAP pre mRNA and no changes in the mRNA half lives . ^^^ Thus , we suggest that 5 LO and FLAP are coordinately regulated in HL 60 cells via mechanisms involving changes in RNA processing . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
FLAP ( 5 lipoxygenase activating protein ) is a novel 18 kDa membrane protein that together with 5 lipoxygenase is required for cellular leukotriene biosynthesis . ^^^ Tony Ford Hutchinson describes a novel class of leukotriene biosynthesis inhibitor , exemplified by MK 0886 , that can bind to FLAP with high affinity , prevent the activation of 5 lipoxygenase by preventing the translocation of the enzyme from the cytosol to the membrane and inhibit leukotriene production . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The so called 5 lipoxygenase activating protein ( FLAP ) inhibitor , MK 886 ( 3 [ 1 ( p chlorobenzyl ) 5 ( isopropyl ) 3 tert butylthioindol 2 yl ] 2 , 2 dimethylpropanoic acid ) , and the iron ligand 5 lipoxygenase inhibitor zileuton ( N ( 1 benzo [ b ] thien 2 ylethyl ) N hydroxy urea ) were also active , but less potent than ZD 2138 with IC 50 values for inhibition of antigen induced leukotriene release in vitro of 9 . 3 + / 3 . 2 microM and 14 . 8 + / 1 . 8 microM , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Reverse transcriptase ( RT ) PCR analysis demonstrated the expression of 5 lipoxygenase , 5 lipoxygenase activating protein ( FLAP ) and LTA 4 hydrolase mRNA in B CLL cells . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The present experiments were undertaken to examine the effect of myocutaneous flap ischemia reperfusion on neutrophil 5 lipoxygenase activity and to define the role of leukotriene B 4 ( LTB 4 ) in postischemic PMN infiltration into such composite tissue grafts . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
All pre B ALL clones expressed genes coding for 5 lipoxygenase activating protein ( FLAP ) , leukotriene A 4 hydrolase and prostaglandin ( PG ) H synthase 1 . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Messenger RNA for FLAP , the 5 lipoxygenase activating protein , was detectable in both cell lines , but only with poly A containing RNA . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Mode of action of the leukotriene synthesis ( FLAP ) inhibitor BAY 10 1005 : implications for biological regulation of 5 lipoxygenase . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Previous studies involving transfection of cDNAs for 5 lipoxygenase activating protein ( FLAP ) and 5 lipoxygenase into osteosarcoma cells have shown that both these proteins are essential for leukotriene synthesis ( Dixon , R . ^^^ Furthermore , differentiation of the human promyelocytic HL 60 cell line towards granulocytic cells following exposure to dimethylsulfoxide is associated with the concurrent induction of both FLAP and 5 lipoxygenase and an increased capacity to synthesize leukotrienes . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In addition , 14b was inactive in a 5 lipoxygenase activating protein ( FLAP ) binding assay at 10 microM . ^^^ Subsequent studies on the aryl thiopyrano [ 2 , 3 , 4 c , d ] indole series of inhibitors led to the discovery of potent dual inhibitors of both FLAP and 5 LO , the most potent of which is 2 [ [ 1 ( 4 chlorobenzyl ) 4 methyl 6 ( quinolin 2 ylmethoxy ) 4 , 5 dihydro 1H thiopyrano [ 2 , 3 , 4 c , d ] indol 2 yl ] methoxy ] phenylacetic acid , 19 . ^^^ Acid 19 has an IC 50 of 100 nM for the inhibition of 5 HPETE production by human 5 LO and is active in a FLAP binding assay with an IC 50 of 32 nM . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
This profile suggests that azelastine may be a novel inhibitor of Ca ( 2+ ) dependent translocation of 5 lipoxygenase from cytosol to the nuclear envelope or a FLAP inhibitor rather than a direct 5 LO inhibitor . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Previous investigations from our laboratory have demonstrated that PBM have reduced 5 lipoxygenase ( 5 LO ) metabolism of arachidonic acid ( AA ) and 5 LO activating protein ( FLAP ) expression as compared to differentiated alveolar macrophages ( AM ) . ^^^ AM from vitamin D 3 deficient rats demonstrated reduced 5 LO metabolism of AA and a parallel reduction in FLAP expression compared to control rats . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Inhibitors of FLAP function prevent translocation of 5 lipoxygenase from cytosol to the membrane and inhibit 5 LO activation . ^^^ One cellular component , a membrane bound peptide termed FLAP , which is necessary for 5 LO activity in intact cells has been recently identified . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The expression of arachidonate 5 lipoxygenase ( 5 LOX , arachidonate : oxygen 5 oxidoreductase ; EC 1 . 13 . 11 . 34 ) and the 5 lipoxygenase activating protein ( FLAP ) genes in lymphoblastoid B and T cell lines was studied at the transcriptional level by reverse transcription PCR analysis . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Northern analysis indicates that ox LDL increases U 937 cell FLAP transcript levels 10 times control levels but did not appear to alter 5 lipoxygenase ( 5 LO ) mRNA levels . ^^^ In contrast , ox LDL increases HL 60 cell transcript levels for FLAP and 5 LO 1 . 5 times and 10 times control levels , respectively . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Importantly , AM contained 40 fold more 5 lipoxygenase activating protein ( FLAP ) than did PBM , which correlated well with the relative abilities of intact AM and PBM to metabolize endogenous AA to leukotrienes . ^^^ The FLAP inhibitor MK 886 was unable to block leukotriene synthesis from exogenous AA in the two cell types , despite its ability to completely inhibit 5 LO metabolism of endogenous AA . ^^^ These observations indicate that , although FLAP is essential for the synthesis of leukotrienes from endogenous AA , perhaps by presenting AA to 5 LO , it is not required for 5 LO metabolism of exogenous AA . ^^^ The differing roles of FLAP in 5 LO metabolism of endogenous versus exogenous AA are consistent with the conclusion that it is the markedly greater expression of FLAP , rather than of 5 LO , that is primarily responsible for the increased leukotriene synthesis from endogenous AA that accompanies PBM differentiation into AM . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The nucleotide and deduced amino acid sequences of the LTC 4 synthase cDNA show no significant homology to GSH S transferases but share 31 % overall amino acid identity with 5 lipoxygenase activating protein ( FLAP ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
While immunoelectron microscopy has identified the nuclear membrane as the site at which 5 LO , as well as 5 LO activating protein ( FLAP ) , are localized in activated cells , the locale of soluble 5 LO in unstimulated cells could not be established by this technique . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The prominent increase in 5 LO activity induced by serum was not concomitant with similar changes in the expression of 5 LO or 5 LO activating protein ( FLAP ) , as judged from analyses of immunoreactive protein and mRNA . ^^^ The results indicate that additional cellular components of importance for 5 LO activity in HL 60 cells become operative after serum treatment , and that mere expression of 5 LO and FLAP is insufficient for high 5 LO activity in intact cells . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Discovery of inhibitors of the 5 lipoxygenase activating protein ( flap ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
It acts through a novel mechanism by a specific interaction with a membrane protein , 5 lipoxygenase activating protein ( FLAP ) , which has been shown to be essential for LT synthesis in inflammatory cells . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Granulocyte / macrophage colony stimulating factor stimulates the expression of the 5 lipoxygenase activating protein ( FLAP ) in human neutrophils . ^^^ In turn , the activation of the 5 LO requires the participation of a recently characterized membrane bound protein , the 5 LO activating protein ( FLAP ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Acid 14d is highly selective as an inhibitor of 5 LO activity when compared to the inhibition of human 15 LO , porcine 12 LO and ram seminal vesicle cyclooxygenase ( IC 50 > 5 microM ) or competition in a FLAP binding assay ( IC 50 > 10 microM ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The intracellular distribution of the enzyme 5 lipoxygenase ( 5 LO ) and 5 lipoxygenase activating protein ( FLAP ) in resting and ionophore activated human leukocytes has been determined using immuno electronmicroscopic labeling of ultrathin frozen sections and subcellular fractionation techniques . 5 LO is a 78 kD protein that catalyzes the conversion of arachidonic acid to leukotrienes . ^^^ In activated leukocytes , both FLAP and 5 LO were localized in the lumen of the nuclear envelope . ^^^ In contrast to FLAP , 5 LO in resting cells could not be visualized along the nuclear envelope . ^^^ These results demonstrate that the nuclear envelope is the intracellular site at which 5 LO and FLAP act to metabolize arachidonic acid , and that ionophore activation of neutrophils and monocytes results in the translocation of 5 LO from a nonsedimentable location to the nuclear envelope . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Western blot analysis demonstrated that the human pancreas contains low levels of 5 lipoxygenase activating protein ( FLAP ) in addition to 5 LO . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The amounts of 5 LO protein , or mRNA for 5 LO or 5 lipoxygenase activating protein ( FLAP ) , were less affected . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The U 937 human promyelocytic cell line does not express 5 lipoxygenase , but does express 5 lipoxygenase activating protein ( FLAP ) . ^^^ Dimethyl sulfoxide ( DMSO ) differentiation of U 937 cells , towards a more mature monocyte macrophage lineage , induces the expression of FLAP but not 5 lipoxygenase . ^^^ We infected viral RNA coding for 5 lipoxygenase into U 937 cells using a retroviral vector and measured the synthesis of 5 lipoxygenase , FLAP , leukotrienes and 5 hydroxyeicosatetraenoic acid ( 5 HETE ) by these cells after stimulation with A 23187 . ^^^ Undifferentiated U 937 cells infected with 5 lipoxygenase RNA expressed 5 lipoxygenase and FLAP but neither leukotrienes nor 5 HETE were detected after these cells were stimulated with A 23187 . ^^^ Exposure of the 5 lipoxygenase infected U 937 cells to DMSO increased the expression of 5 lipoxygenase and FLAP , and these cells produced leukotrienes and 5 HETE in response to A 23187 . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We have utilized HL 60 cells to study the mechanisms regulating expression of 5 lipoxygenase and the recently described 18 kDa membrane protein , 5 lipoxygenase activating protein ( FLAP ) . ^^^ Examination of the levels of the transcript encoding 5 lipoxygenase and FLAP demonstrated that differentiation of HL 60 cells into granulocytes resulted in a co ordinate induction of 5 lipoxygenase and FLAP mRNA . ^^^ In contrast , differentiation of HL 60 cells into monocytes resulted in discordant regulation of 5 lipoxygenase and FLAP mRNA . ^^^ Treatment with 1 , 25 dihydroxyvitamin D 3 resulted in a 6 fold increase in 5 lipoxygenase mRNA and a 1 . 3 fold increase in FLAP mRNA , while treatment with phorbol ester did not induce 5 lipoxygenase mRNA but did increase FLAP mRNA 2 fold . ^^^ The transcriptional rate of the 5 lipoxygenase and FLAP genes did not change upon Me2SO or 1 , 25 dihydroxyvitamin D 3 treatment , suggesting that the increase of the mRNA coding for these proteins was not due to transcriptional activation of their respective genes . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Compound 44 is highly selective for 5 LO when compared to the inhibition of human FLAP , porcine 12 LO , and also ram seminal vesicle cyclooxygenase . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
However , the mechanism by which FLAP activates 5 LO has not been determined . ^^^ These studies suggest that FLAP may activate 5 LO by specifically binding arachidonic acid and transferring this substrate to the enzyme . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Subcellular fractions were also examined for the presence of the 5 LO activating protein ( FLAP ) . ^^^ Consistent with the absence of proteins , the mRNAs for 5 LO and FLAP were undetectable by reverse transcriptase polymerase chain reactions analysis . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Previous cloning of the cDNA for human LTC 4 synthase demonstrated significant homology of its amino acid sequence to that of 5 lipoxygenase activating protein ( FLAP ) but none to that of the GSH S transferase super family . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The gene transcription of 5 lipoxygenase ( 5 LO ) and 5 lipoxygenase activating protein ( FLAP ) in renal tissue of patients with IgA nephropathy and mesangial proliferative glomerulonephritis were analyzed by amplification of reverse transcribed mRNA with polymerase chain reaction ( PCR ) . ^^^ The level of expression was determined by analysis of the PCR products of 5 LO , FLAP , and beta actin . ^^^ Forty percent of the patients expressed both 5 LO and FLAP . ^^^ Relative to beta actin , FLAP expression ( 0 . 42 + / 0 . 21 ) was higher than 5 LO ( 0 . 14 + / 0 . 10 ) . ^^^ Comparison of clinical data showed that patients who expressed 5 LO and FLAP had a lower glomerular filtration rate and an increased level of blood urea nitrogen , serum creatinine , and proteinuria . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Arachidonate 5 lipoxygenase and its activating protein : prominent hippocampal expression and role in somatostatin signaling . 5 Lipoxygenase activating protein ( FLAP ) is an 18 kDa integral membrane protein required , in peripheral cells , for the activation of 5 lipoxygenase ( 5 LO ) and for the resulting synthesis of leukotrienes from arachidonic acid . ^^^ In the present study , we used reverse transcriptase polymerase chain reaction , in situ hybridization , and immunohistochemistry to demonstrate that 5 LO and FLAP are expressed in various regions of the rat brain , including hippocampus , cerebellum , primary olfactory cortex , superficial neocortex , thalamus , hypothalamus , and brainstem . ^^^ In the latter we demonstrate the colocalization of 5 LO and FLAP in CA 1 pyramidal neurons . ^^^ Our results provide necessary evidence for the presence and signaling role of 5 LO and FLAP in central neurons and strongly support their proposed participation in somatostatin receptor transmembrane signaling . . ^^^ Arachidonate 5 lipoxygenase and its activating protein : prominent hippocampal expression and role in somatostatin signaling . 5 Lipoxygenase activating protein ( FLAP ) is an 18 kDa integral membrane protein required , in peripheral cells , for the activation of 5 lipoxygenase ( 5 LO ) and for the resulting synthesis of leukotrienes from arachidonic acid . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We studied the expression and regulation of LX genes ( 12 LX , 5 LX , and 15 LX ) and the 5 lipoxygenase activating protein ( FLAP ) in human mononuclear cells ( MNC ) and granulocytes using a quantitative reverse transcription polymerase chain reaction ( RT PCR ) technique . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Inhibition of 5 lipoxygenase activating protein ( FLAP ) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats . ^^^ Rats hypoxic for 4 wk developed pulmonary hypertension increased translocation of the lung 5 LO from the cytosol to the membrane fraction and increased levels of lung tissue 5 lipoxygenase activating protein ( FLAP ) . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
However , there was a reduction ( approximately twofold ) in 5 LO protein expression in both the normal and the low CD 4 subsets . 5 LO activating protein ( FLAP ) expression was unchanged in cells from the normal CD 4 HIV group , but was decreased threefold in the two groups with low CD 4 counts . ^^^ These observations indicate that there is a graded defect in the 5 LO metabolic capacity of AM from HIV infected subjects , with decreased expression of only 5 LO in the normal CD 4 group , and decreased expression of both 5 LO and FLAP in the low CD 4 group . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The expression of arachidonate 5 lipoxygenase ( 5 LOX , arachidonate : oxygen 5 oxydoreductase ; EC 1 . 13 . 11 . 34 ) and the 5 lipoxygenase activating protein ( FLAP ) genes in osteoarthritis and RA synoviocytes was studied at the transcriptional level by reverse transcription polymerase chain reaction ( RT PCR ) methodology . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Human monocytes lose 5 lipoxygenase and FLAP as they mature into monocyte derived macrophages in vitro . ^^^ Previous studies in mononuclear phagocytes have shown that macrophages have substantially greater 5 lipoxygenase activity than monocytes and that this is associated with greater amounts of 5 lipoxygenase and its activating protein ( FLAP ) . ^^^ Immunoblot and Northern blot analysis revealed that immunoreactive protein and mRNA for both 5 lipoxygenase and FLAP were significantly decreased over time . ^^^ These studies demonstrate that in vitro differentiation of monocytes into a macrophage phenotype is not accompanied by the enhanced expression of 5 lipoxygenase and FLAP seen in macrophages derived from in vivo sources . ^^^ In fact , baseline expression of 5 lipoxygenase and FLAP by monocytes is lost in vitro . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Western blot analyses of myelocytic leukemia cell lines , HL 60 # 7 and HL 60 , differentiated towards eosinophilic or neutrophilic cell types , respectively , demonstrated that as myelocytic cells differentiate towards eosinophils or neutrophils , the protein levels of cytosolic phospholipase A 2 ( cPLA 2 ) remain constant , whereas 5 lipoxygenase and 5 lipoxygenase activating protein ( FLAP ) levels are simultaneously elevated . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Specific inhibitors of 5 lipoxygenase and 5 lipoxygenase activating protein ( FLAP ) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these features of allergic pulmonary inflammation . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Immunoblot analysis showed that the steady state expression of 5 LO and 5 lipoxygenase activating protein ( FLAP ) also increased in an age dependent manner . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
At 7 days , the cells contained mRNA and sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot signals for cytosolic phospholipase A 2 ( cPLA 2 ) , 5 lipoxygenase ( 5 LO ) , and 5 lipoxygenase activating protein ( FLAP ) , but lacked LTC4S and did not generate cysteinyl leukotrienes when stimulated with 20 mumol / L calcium ionophore . ^^^ At 28 days , progressive eosinophil maturation was accompanied by further increments in 5 LO , FLAP , and LTC4S proteins , and by the ionophore induced production of 94 . 6 + / 9 . 0 pmol cysteinyl leukotrienes / 10 ( 6 ) eosinophil lineage cells ( n = 6 ) . ^^^ Cells selected for CD 34 expression lacked detectable 5 LO / LTC4S pathway proteins , and with culture generally expressed immunodetectable cPLA 2 and 5 LO proteins by 3 days , FLAP protein by 7 days , and LTC4S protein by 10 days . ^^^ Thus , during the development of eosinophils in vitro , cPLA 2 , 5 LO , and FLAP are expressed before LTC4S . ^^^ Once the lineage is established by morphologic criteria , the eosinophilopoietic cytokines mediate upregulation of FLAP and LTC4S , members of a newly recognized gene family , and of 5 LO , during ongoing cell maturation . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
A study was conducted to examine the expression of the mRNA for the enzymes of the eicosanoid pathways ( 5 lipoxygenase ( 5 LO ) , 5 lipoxygenase activating protein ( FLAP ) , cyclo oxygenases 1 and 2 ( COX 1 , COX 2 ) , and 15 lipoxygenase ( 15 LO ) ) in normal subjects and in patients with stable atopic asthma and stable cystic fibrosis . ^^^ METHODS : Reverse transcription polymerase chain reaction ( RT PCR ) was used to examine the expression of total RNA for 5 LO , FLAP , COX 1 , COX 2 , and 15 LO in peripheral blood polymorphonuclear cells and mononuclear cells from the three subjects groups . ^^^ RESULTS : The expression of mRNA for 5 LO and FLAP was similar in normal subjects and in patients with asthma and cystic fibrosis . ^^^ CONCLUSIONS : The increased leukotriene production in asthma and cystic fibrosis is not explained by an increase in transcription of 5 LO and FLAP . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Role of the 5 lipoxygenase activating protein ( FLAP ) in murine acute inflammatory responses . ^^^ The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5 lipoxygenase ( 5 LO ) , which catalyzes the first steps in the synthesis of leukotrienes , but also on expression of a nuclear membrane protein termed the 5 LO activating protein ( FLAP ) . ^^^ To determine whether these differences relate solely to a deficit in leukotriene production , or whether they reflect an additional role for FLAP in inflammation , we compared the FLAP deficient mice to 5 LO deficient animals . ^^^ Evaluation of mice lacking FLAP and 5 LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production . . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
This paper briefly deals with compounds influencing leukotriene biosynthesis and activity . 5 Lipoxygenase inhibitors ( e . g . , zileuton ) and FLAP inhibitors ( e . g . , quiflapon ) hinder biosynthesis of all leukotrienes . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Identification and characterization of a novel microsomal enzyme with glutathione dependent transferase and peroxidase activities . 5 Lipoxygenase activating protein ( FLAP ) , leukotriene C 4 ( LTC 4 ) synthase , and microsomal glutathione S transferase 2 ( microsomal GST 2 ) are all members of a common gene family that may also include microsomal GST 1 . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Human peripheral blood monocytes ( HPBMs ) express 5 lipoxygenase ( 5 LO ) and 5 LO activating protein ( FLAP ) , and hence have an ability to synthesize proinflammatory leukotrienes ( LTs ) . ^^^ Regulation of 5 LO and FLAP expression is a major determinant of cellular LT synthesis . ^^^ We examined the effects of proinflammatory [ interleukin ( IL ) 1 and interferon ( IFN ) gamma ] and T helper lymphocyte subset 2 ( TH 2 ; IL 4 and IL 13 ) cytokines on ( 1 ) LTB 4 production , and ( 2 ) 5 LO and FLAP expression in HPBMs . ^^^ IL 1 modestly increased FLAP mRNA and significantly increased 5 LO mRNA steady state levels at 24 and 36 hours of incubation , respectively . ^^^ IFN gamma did not change the mRNA or protein expression of either 5 LO or FLAP . ^^^ |
|
Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Differential effects of cell density on 5 lipoxygenase ( 5 LO ) , five lipoxygenase activating protein ( FLAP ) and interleukin 1 beta ( IL 1 beta ) expression in human neutrophils . ^^^ We have analyzed the effect of cellular density of 5 Lipoxygenase ( 5 LO ) , 5 lipoxygenase activating protein ( FLAP ) and interleukin 1 beta ( IL 1 beta ) gene expression in neutrophils from healthy subjects under culture conditions of low and high cell density . ^^^ By using RT PCR techniques , we have found that 5 LO mRNA accumulation decreased in cells cultured at high density , while FLAP mRNA is not affected . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In addition , tenidap impaired 5 LO translocation from cytosol to its membrane bound docking protein ( FLAP ) which occurs when human neutrophils are stimulated with calcium ionophore , indicating a second mechanism for inhibiting the 5 LO pathway . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We observed an arachidonic acid metabolism via 5 lipoxygenase pathway despite the lack of FLAP mRNA expression and that certain eicosanoids such as hydroperoxy and hydroxyeicosatetraenoic acids stimulate chloride secretion . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Cloning of LTC 4 synthase cDNA reveals amino acid homology with 5 lipoxygenase activating protein ( FLAP ) and newly identified microsomal glutathione S transferase 2 ( mGST 2 ) but not with cytosolic GSTs or mGST 1 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The aim of the study is to study the efficacy of a potent 5 lipoxygenase activating protein inhibitor ( FLAP ) , BAY y 1015 in a dextran sulfate model of mouse colitis . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Differential regulation of cyclo oxygenase 2 and 5 lipoxygenase activating protein ( FLAP ) expression by glucocorticoids in monocytic cells . 1 . ^^^ The objective of the present study was to determine the effects of dexamethasone on key constituents of prostaglandin and leukotriene biosynthesis , cyclo oxygenase 2 ( COX 2 ) and 5 lipoxygenase activating protein ( FLAP ) . ^^^ However , the glucocorticoid mediated induction of FLAP may provide a mechanism to maintain leukotriene biosynthesis through more efficient transfer of arachidonic acid to the 5 lipoxygenase reaction , in spite of inhibitory effects on other enzymes of the biosynthetic pathway . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
To identify possible inhibitors of LTC 4 synthase , synthetic compounds known to inhibit other proteins in the leukotriene biosynthetic pathway ( 5 lipoxygenase activating protein , FLAP , and 5 lipoxygenase , 5 LO ) or to antagonize leukotriene receptors ( cys LT 1 ) were tested for activity against LTC 4 synthase . ^^^ These results implicate that compounds that bind competitively to arachidonic acid binding sites on FLAP and 5 LO recognize motifs that are also weakly conserved on the binding site of LTC 4 synthase . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Enriched primary LCs were also found to contain 5 LO activating protein ( FLAP ) , leukotriene ( LT ) C 4 synthase , and LTA 4 hydrolase . ^^^ By contrast , 5 LO , FLAP , and LTC 4 synthase were undetectable or largely reduced , but LTA 4 hydrolase transcripts and protein were identified in ECs depleted of LCs . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The leukotrienes LTB 4 and LTC 4 are assigned to inflammation . 5 lipoxygenase inhibitors which inhibit the synthesis of LTA 4 being the precursor of both LTB 4 and LTC 4 appear to have only a limited antiinflammatory potential . 5 lipoxygenase inhibitors are represented by direct and indirect inhibitors , the latter competing with substrate transfer from the five lipoxygenase activating protein ( FLAP ) to the 5 lipoxygenase enzyme . 5 lipoxygenase inhibition under experimental condition results in inhibition of edema formation , neutrophil infiltration , smooth muscle contraction after antigen challenge and prevention of early and late allergic reactions . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Lipoxygenase and 5 lipoxygenase activating protein ( FLAP ) immunoreactivity in lungs from patients with primary pulmonary hypertension . ^^^ Leukotriene production by perivascular and alveolar macrophages relies on activation of 5 lipoxygenase ( 5 LO ) , with translocation of the enzyme to the nuclear membrane , and association with the 5 LO activating protein ( FLAP ) . ^^^ Using immunohistochemical staining , we localized and semi quantitatively estimated the abundance of 5 LO and FLAP in lungs obtained from patients with PPH , patients with interstitial lung disease ( ILD ) , and normal control subjects . ^^^ Expression of 5 LO and FLAP was prominent in alveolar macrophages in both the normal and PPH lungs ; however , alveolar macrophages were more frequently clustered in the vicinity of remodeled blood vessel in PPH . ^^^ Medium and small size pulmonary arteries in PPH showed more abundant FLAP expression than in control and ILD lungs . 5 LO expression in small arteries in PPH was more intense than in control and ILD patients . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Following a rise in intracellular calcium , 5 LO translocates to a membrane where it reacts with arachidonic acid via an 18 kD protein ( FLAP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In 16HBE transformed human bronchial epithelial cells , histamine stimulated interleukin ( IL ) 8 mRNA and protein secretion , and this histamine stimulation was inhibited by the H 1 receptor antagonist diphenhydramine ( DPH ) , by the inhibitor of 5 lipoxygenase activating protein ( FLAP ) MK 886 , by the 5 lipoxygenase inhibitor Zileuton , and by dexamethasone . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The present investigation describes the ability of human 5 lipoxygenase activating protein ( FLAP ) to activate a plant 5 lipoxygenase . ^^^ The presence of an active recombinant human FLAP in the 100000xg membrane fraction of infected Sf 9 cells led to a specific increase in 9 hydroperoxyoctadecadienoic acid ( 9 HPOD ) synthesis ( +68 % ) or in 5 hydroperoxyeicosatetraenoic acid ( 5 HPETE ) synthesis ( +68 % ) , after action of Solanum tuberosum tuber 5 lipoxygenase ( S . t . ^^^ In conclusion , this study demonstrates that a recombinant human FLAP can stimulate a lipoxygenase other than mammalian 5 lipoxygenase ( S . t . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Cells showing positive antibody binding to 5 LO , FLAP ( 5 lipoxygenase activating protein ) , and leukotriene A 4 hydrolase were also present in the coronary arteries and had a similar distribution to macrophages . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Therefore , we examined the expression of 5 LO and FLAP mRNAs in the peripheral blood leukocytes ( PBL ) of 10 asthmatics and 10 controls . ^^^ Both 5 LO and FLAP mRNAs of PBL in the asthmatic group were found to be significantly increased compared with those in the control group . ^^^ These data suggest that up regulation of 5 LO and FLAP mRNAs might be involved in the increased leukotriene synthesis and play an important role in the pathogenesis of asthma . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The effects on the voltage gated ( IK ) and Ca2+ activated ( 1 ( K , Ca ) ) K+ currents in rat arterial myocytes of the 5 lipoxygenase activating protein ( FLAP ) inhibitor MK 886 , and its inactive analogue L 583 , 916 were evaluated . 2 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Immunostaining for 5 lipoxygenase , its activating protein ( FLAP ) , LTA 4 hydrolase , cyclooxygenase ( COX ) 1 , and COX 2 did not differ . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The effect of 5 lipoxygenase activating protein ( FLAP ) on substrate utilization by 5 lipoxygenase . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Leukotriene synthesis in both eosinophils and neutrophils was suppressed by the 5 lipoxygenase activating protein ( FLAP ) inhibitor , MK 886 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In view of the partial structural similarity between MGST 1 , leukotriene C 4 synthase , and 5 lipoxygenase activating protein ( FLAP ) , it was of interest that leukotriene C 4 synthesis inhibitors ( which antagonize FLAP ) also displayed significant inhibition ( e . g . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
However , the sources for ROIs in various cell types are yet to be determined and might include 5 lipoxygenase ( 5 LOX ) and NADPH oxidase . 5 LOX and 5 LOX activating protein ( FLAP ) are coexpressed in lymphoid cells but not in monocytic or epithelial cells . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Inhibitors of 5 lipoxygenase activating protein ( FLAP ) have been found to induce apoptosis . ^^^ FL5 . 12 cells contained a substantial amount of FLAP protein and mRNA but surprisingly had no measurable 5 lipoxygenase protein or 5 , 12 , or 15 lipoxygenase activity . ^^^ The absence of 5 lipoxygenase in cells containing FLAP , the lower level of FLAP in bcl xL cells , the apoptosis inducing activity of MK 886 , and the rapid loss of bcl xL and bcl 2 proteins after treatment with MK 886 strongly indicate that FLAP has activities unrelated to lipoxygenase and suggest a possible functional or regulatory link between these proteins , which share similar subcellular localizations . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Five lipoxygenase activating protein ( FLAP ) is usually described as an essential protein to activate the leukotriene ( LTs ) synthesis via the 5 lipoxygenase pathway . ^^^ In the enterocyte model HT 29 cl . 19A cell line , 5 lipoxygenase metabolism was found despite the lack of FLAP expression . ^^^ In FLAP cDNA transfected HT 29 cl . 19A cells , FLAP expression led to an increase in cyclooxygenase pathway products ( mainly PGE 2 ) without an increase in 5 lipoxygenase metabolism . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
This was associated with increased 5 LO activating protein ( FLAP ) ( 357+ / 29 . 5 % ) , and 5 LO expression ( 188+ / 31 . 3 % ) . ^^^ Culture of AM for 3 days resulted in a greater decrement in LTB 4 synthesis ( LTB 4 15 . 4+ / 6 . 9 % of day 1 ) than in PM ( 54 . 7+ / 8 . 3 % of day 1 ) , suggesting a greater dependence of AM 5 LO metabolism on ALF . 5 LO and FLAP expression decreased to a greater degree in AM than PM in culture . ^^^ Furthermore , AM cultured with ALF maintained their LT synthetic capacity , FLAP and 5 LO expression compared with control cells cultured in medium alone . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : To determine whether selective 5 lipoxygenase ( 5 LO ) inhibition decreases expression of adhesion molecules ( beta 2 integrins ) on systemic neutrophils , decreases neutrophil infiltration in ischemic flap tissue , and improves flap survival . ^^^ The treated groups received zileuton , a 5 LO inhibitor , orally during flap ischemia . ^^^ CONCLUSIONS : Systemic administration of a 5 LO inhibitor is effective in reducing ischemia reperfusion injury in flap tissue . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
This review summarizes the biochemistry of the 5 lipoxygenase pathway , the pharmacology of FLAP and 5 lipoxygenase inhibitors and discusses possible criteria for the development of these drugs . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Lipoxygenase metabolites may be involved in human parturition . 5 lipoxygenase ( 5 LOX ) catalyses the first steps in the synthesis of leukotrienes from arachidonic acid , and its activity is dependent on 5 LOX activating protein ( FLAP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We hypothesized that IL 5 induces the expression of 5 LO and / or its activating protein FLAP in eosinophils , and that this might be modulated by anti inflammatory corticosteroids . ^^^ Thus , IL 5 increases FLAP expression and translocates 5 LO to the nucleus in normal blood eosinophils in vitro . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In contrast , the complete inhibition of leukotriene B 4 production by 5 lipoxygenase and 5 lipoxygenase activating protein ( FLAP ) inhibitors had no effect on cyclic AMP levels . ^^^ These data demonstrate that selective phosphodiesterase 4 inhibitors can inhibit the fMLP induced leukotriene B 4 biosynthesis in human polymorphonuclear leukocytes with a potency similar or greater than that of potent 5 lipoxygenase or FLAP inhibitors . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Here we report that 4 bromophenacyl bromide ( 4 BPB ; an inhibitor of PLA 2 ) , nordihydroguaretic acid ( NDGA ; a 5 lipoxygenase inhibitor ) , as well as MK 886 [ an inhibitor of 5 lipoxygenase activating protein ( FLAP ) ] interfere with TNF induced NF kappaB mediated transactivation . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
They can block the 5 lipoxygenase enzyme and / or 5 lipoxygenase activating proteine ( FLAP ) , or can block the cysteinyl leukotriene receptors on the cell surface . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Four synthesizing enzymes , cytosolic phospholipase A 2 ( cPLA 2 ) , 5 lipoxygenase ( 5 LO ) , LTA 4 hydrolase and LTC 4 synthase , and an enzyme associated protein , 5 lipoxygenase activating protein ( FLAP ) are involved in the generation of LTC 4 and LTB 4 . ^^^ Messenger RNA abundance for 5 LO , LTC 4 synthase and LTA 4 hydrolase was increased , that for FLAP was stable , but that for cPLA 2 was decreased . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We analyzed the expression of five AA metabolizing enzymes as well as 5 lipoxygenase activating protein ( FLAP ) in a panel of human epithelial cancer cell lines ( n = 20 ) using reverse transcription PCR . ^^^ 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 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Prior treatment with the 5 lipoxygenase activating protein ( FLAP ) inhibitor , 3 [ 1 ( p chlorobenzyl ) 5 ( isopropyl ) 3 t butylthioindol 2 yl ] 2 , 2 d imethyl propanoic acid sodium ( MK 886 ) ( 10 microg kg ( 1 ) , i . v . ) , the leukotriene receptor antagonist , benzenemethanol a pentyl 3 ( 2 quinolinylmethoxy ) ( REV 5901 ) ( 1 mg kg ( 1 ) , i . v . ) , or the glutathione S transferase inhibitor , ethacrynic acid ( 1 mg kg ( 1 ) , i . v . ) , delayed by 60 min the onset of general extravasation caused by 1 mg kg ( 1 ) histamine . 4 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
METHODS : We conducted an open label , pilot study of the short term effects of leukotriene biosynthesis inhibition using an orally active 5 LO activating protein ( FLAP ) antagonist ( MK 591 ) on glomerular function in patients with glomerulonephritis . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We found increased levels of 5 LO mRNA and protein in hippocampus and cerebellum of glucocorticoid treated rats ; 5 LO activating protein ( FLAP ) mRNA content was not affected . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Substituted indoles as potent and orally active 5 lipoxygenase activating protein ( FLAP ) inhibitors . ^^^ This paper reports on the SAR investigation of inhibitors of 5 lipoxygenase activating protein ( FLAP ) based on MK 0591 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Pharmacologically , there are two different ways of blocking the action of leukotrienes : inhibiting their production by blocking 5 lipoxygenase or its activating protein , 5 lipoxygenase activating protein ( FLAP ) , ( inhibitors ) or by blocking their receptors ( antagonists ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Novel polymorphism of the 5 lipoxygenase activating protein ( FLAP ) promoter gene associated with asthma . ^^^ The human 5 lipoxygenase activating protein ( FLAP ) gene is one of the key genes involved in the production of the cysteinyl leukotrienes . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Expression of 5 LO ( 51 . 2 % + / 8 . 8 % of control ) , and 5 LO activating protein ( FLAP ) ( 48 . 5 % + / 8 . 0 % of control ) was reduced in parallel . ^^^ PBM 5 LO metabolism ex vivo was selectively increased after GM CSF therapy and was associated with increased 5 LO and FLAP expression . ^^^ PMN leukotriene B ( 4 ) ( LTB ( 4 ) ) synthesis was also augmented and associated with increased 5 LO , FLAP , and cytosolic phospholipase A ( 2 ) expression . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Inhibition of 5 lipoxygenase ( 5 LO ) with BWA4C and of 5 LO activating protein ( FLAP ) with MK 886 abolished GM CSF and DEX induced neutrophil survival . ^^^ These findings demonstrate reversal of LPS , GM CSF , and DEX induced neutrophil survival by LTB ( 4 ) receptor antagonism and inhibitors of 5 LO and FLAP . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The aim of this report is to describe the differential gene expression of both the known pro inflammatory genes 5 lipoxygenase and 5 lipoxygenase activating protein ( FLAP ) and novel cDNA sequences in eosinophils derived from clinical samples . ^^^ Expression of 5 lipoxygenase was not found to vary between the different eosinophil populations , whereas FLAP was induced by treatment with the cytokine cocktail in both primary eosinophils and the eosinophilic cell line AML 14 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Primary cultures of rat cerebellar granule cells as a model to study neuronal 5 lipoxygenase and FLAP gene expression . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
For the first time we show that , in mouse peritoneal macrophages , ovalbumin immunization induces an increase in cyclooxygenase 2 ( COX 2 ) and 5 lipoxygenase activating protein ( FLAP ) expression whereas it inhibits cytosolic phospholipase A ( 2 ) ( cPLA 2 ) expression . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The fact that LPS inhibited LT synthesis from endogenous AA more than from exogenous AA suggested an effect on 5 LO activating protein ( FLAP ) . ^^^ No effect on the expression of either 5 LO or FLAP proteins was observed . ^^^ We conclude that prolonged exposure to LPS impairs AM 5 LO metabolism by NO mediated suppression of both 5 LO and FLAP function . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We used in situ PCR in this model of human asthma to detect lung mRNA for 5 lipoxygenase ( 5 LO ) and 5 LO activating protein ( FLAP ) , key proteins necessary for leukotriene synthesis . ^^^ After fixation , the tissue sections underwent protease and RNase free DNase digestion , before in situ RT PCR using target specific cDNA amplification . 5 LO and FLAP specific mRNA was visualized by a digoxigenin detection system , and positive cells were analyzed by morphometry . 5 LO and FLAP specific mRNA and protein were associated primarily with eosinophils and alveolar macrophages in the airways and pulmonary blood vessels in OVA sensitized / challenged mice . 5 LO and FLAP protein expression increased on a per cell basis in alveolar macrophages of OVA treated mice compared with saline controls . ^^^ Pulmonary blood vessel endothelial cells were also positive for 5 LO , FLAP mRNA , and protein . 5 LO inhibition significantly decreased 5 LO and FLAP specific mRNA and protein expression in the lung inflammatory cells and endothelial cells . ^^^ These studies demonstrate a marked increase in key 5 LO pathway proteins in the allergic lung inflammatory response and an important immunomodulatory effect of leukotriene blockade to decrease 5 LO and FLAP gene expression . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Granulocyte macrophage colony stimulating factor ( GM CSF ) plus tumor necrosis factor alpha ( TNF alpha ) promoted DC differentiation and induced a strong rise in 5 LO and FLAP expression . ^^^ TGF beta 1 further increased 5 LO and FLAP expression , recruited additional cells into the 5 LO ( + ) DC population , and promoted production of 5 hydroxyeicosatetraenoic acid and leukotriene B ( 4 ) in response to calcium ( Ca ( ++ ) ) ionophore A 23187 . ^^^ Scattered 5 LO and FLAP in situ hybridization signals were recorded in cells of paracortical T lymphocyte rich areas and germinal centers ( GCs ) of lymph nodes ( LNs ) and tonsil and in cells of mucosae overlying the Waldeyer tonsillar ring . 5 LO protein localized to both CD1a ( + ) immature DCs and to CD 83 ( + ) mature interdigitating DCs of T lymphocyte rich areas of LNs and tonsil . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
None of these cytokines , either alone or in combination , substantially altered the levels of cytosolic phospholipase A ( 2 ) ( cPLA ( 2 ) ) , 5 lipoxygenase ( 5 LO ) , or 5 LO activating protein ( FLAP ) protein expression by hMCs . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : We used ovalbumin sensitized rats to study the expression of cytosolic phospholipase A 2 ( cPLA 2 ) , 5 lipoxygenase ( 5 LO ) and 5 lipoxygenase activating protein ( FLAP ) in peritoneal macrophages during active sensitization . ^^^ METHODS : cPLA 2 , 5 LO and FLAP expression was assessed by Western blotting . ^^^ RESULTS : Ovalbumin sensitization of rats increased cPLA 2 , 5 LO and FLAP expression in peritoneal macrophages . ^^^ IL 4 induced FLAP expression in cPM but had no effect on cPLA 2 and 5 LO expression . ^^^ The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA 2 , 5 LO and FLAP that , however , is not able to lead to modifications of macrophage AA metabolism in any circumstance . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In season biopsies had 2 fold more cells immunostaining for 5 LO ( p = 0 . 02 ) , 5 LO activating protein ( FLAP ; p = 0 . 04 ) , and leukotriene ( LT ) A 4 hydrolase ( p = 0 . 05 ) , and 4 fold more for the terminal enzyme for cysteinyl leukotriene synthesis , LTC 4 synthase ( p = 0 . 02 ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Human monocytes incubated for 24 , 48 , and 72 h with IL 4 ( 10 ng / ml ) were stimulated with Ca2+ ionophore A 23187 ( calcimycin ; 5 microM ) or opsonized zymosan . 15 ( S ) hydroxyeicosatetraenoic acid [ 15 ( S ) HETE ] , LTB 4 , and arachidonic acid ( AA ) release were measured by high performance liquid chromatography / radioimmunoassay , liquid chromatography / tandem mass spectrometry ( LC / MS / MS ) , or gas chromatography / mass spectrometry . 15 LO activity was evaluated in AA treated monocytes . 15 LO , 5 lipoxygenase ( 5 LO ) and 5 LO activating protein ( FLAP ) expression were analyzed by reverse transcription polymerase chain reaction . ^^^ IL 4 treatment induced 15 LO enzymatic activity as well as 15 LO mRNA , but did not affect either 5 LO or FLAP mRNA expression in monocytes . ^^^ Whereas this effect did not reflect changes in 5 LO and FLAP mRNA expression , synthetic 15 ( S ) HETE was able to significantly inhibit the synthesis of LTB 4 , without affecting AA release . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Transformation of arachidonic acid to LTA 4 is catalyzed by the enzyme 5 lipoxygenase and facilitated by FLAP . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Skin biopsies were taken at 6 h to determine numbers of mast cells , eosinophils , basophils , Langerhans ' cells , and monocytes / macrophages , and the expression of COX 1 , COX 2 , 5 LO and FLAP . ^^^ Immunocytochemical examination of biopsies taken at 8 h showed increased numbers of eosinophils and basophils and in COX 2 , 5 LO and FLAP , but not COX 1 . ^^^ Expression of 5 LO and FLAP was associated primarily with eosinophils . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In stimulated human PMN , activation of 5 LO involves calcium , p 38 MAP kinase ( p 38 ) phosphorylation , and translocation of 5 LO from the cytosol to nuclear membranes containing the 5 LO activating protein ( FLAP ) . ^^^ The 5 LO translocation was also inhibitable by the FLAP antagonist MK 0591 and correlated with LT biosynthesis in all experimental conditions tested . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
To investigate the involvement of cysteinyl leukotrienes and prostanoids in these symptoms , bronchial biopsy specimens from 9 normal subjects ( nonatopic and with no history of chronic lung disease ) were immunostained for 5 lipoxygenase ( 5 LO ) and cyclooxygenase ( COX ) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16 . 5 LO positive cell counts increased 9 fold ( from 0 . 48 to 4 . 4 cells / mm ( 2 ) ; P < . 05 ) , and 5 LO activating protein ( FLAP ) positive cell counts increased 3 . 6 fold ( from 1 . 8 to 6 . 5 cells / mm ( 2 ) ; P = . 09 ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The enzyme activity of LTC4S is augmented by Mg2+ and inhibited by Co2+ and the function of 5 lipoxygenase ( LO ) activating protein ( FLAP ) inhibitor MK 886 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Hyperoxia increases protein mass of 5 lipoxygenase and its activating protein , flap , and leukotriene B ( 4 ) output in newborn rat lungs . ^^^ In this study , the authors examined in newborn rat lung tissues the release of leukotriene B ( 4 ) ( LTB ( 4 ) ) from tissue explants in vitro , the protein expression of the LT synthesizing enzyme , 5 lipoxygenase ( 5 LO ) , and its activating protein ( FLAP ) , and the effects of in vivo hyperoxic exposure ( > 95 % O ( 2 ) ) on these parameters . ^^^ Western immunoblotting of lung tissue showed that 5 LO and FLAP protein mass increased ( P < . 05 ) from days 4 to 14 . ^^^ Immunohistochemistry localized 5 LO and FLAP mainly to alveolar macrophages on day 14 , but some staining was evident in parenchymal tissue . ^^^ These data show that hyperoxia increases LTB ( 4 ) output , as well as protein levels of 5 LO and FLAP , in newborn rat lungs during early postnatal life . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The same effect was observed with MK 886 , a 5 LO activating protein ( FLAP ) specific inhibitor . ^^^ We demonstrate that IL 10 suppresses the production of LTB 4 from DC by inhibiting FLAP protein expression without any effect on 5 LO and cytosolic phospholipase A 2 . ^^^ Taken together , our results suggest links between DC cyclooxygenase and 5 LO pathways during the inflammatory response , and FLAP is a key target for the PG induced IL 10 suppressive effects . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
MK 886 , an inhibitor of 5 lipoxygenase activating protein ( FLAP ) , and the lipoxygenase ( LOX ) inhibitors baicalein and nordihydroguaiaretic acid ( NDGA ) , induce apoptosis by mechanisms independent of both LOX and FLAP . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We examined expression of the 5 lipoxygenase activating protein ( FLAP ) , which is critical for inflammatory cell leukotriene synthesis . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
MK 886 , a strong proapoptotic agent , is an inhibitor of 5 lipoxygenase ( LOX ) through binding to the 5 LOX activating protein ( FLAP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Toxicity of human monocytic THP 1 cells and microglia toward SH SY5Y neuroblastoma cells is reduced by inhibitors of 5 lipoxygenase and its activating protein FLAP . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
In intact cells , the helper protein 5 LO activating protein ( FLAP ) is necessary for efficient enzyme utilization of endogenous substrate . ^^^ Here we review the molecular and cellular aspects of the expression , function , and regulation of 5 LO and FLAP . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : 5 Lipoxygenase ( 5 LO ) and 5 lipoxygenase activating protein ( FLAP ) are essential for cysteinyl leukotriene ( cys LT ) production , critical mediators in asthma . ^^^ OBJECTIVE : We sought to identify novel promoter polymorphisms within the FLAP ( ALOX5AP ) gene promoter and test the role of these and the previously identified 5 LO ( ALOX 5 ) Sp 1 promoter polymorphism in asthma susceptibility . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Roles of 5 lipoxygenase activating protein in cell proliferation and apoptosis . 5 Lipoxygenase activating protein ( FLAP ) functions as a facilitator of 5 lipoxygenase ( 5 LOX ) activity . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Kupffer cells were the only liver cell type endowed with a metabolically active 5 LO pathway ( i . e . , expressed mRNAs for 5 LO , 5 LO activating protein [ FLAP ] , and leukotriene [ LT ] C 4 synthase and generated LTB 4 and cysteinyl LTs ) . ^^^ Both the selective 5 LO inhibitor AA 861 and the FLAP inhibitor BAY 10 1005 markedly reduced the number of Kupffer cells in culture . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : The binding of 5 lipoxygenase ( 5 LO ) to the 5 LO activating protein ( FLAP ) is a prerequisite for subsequent formation of leukotrienes ( LT ) from arachidonic acid . ^^^ METHODS : Diabetic rats were treated for 4 weeks with FLAP ( BAY 10 1005 , 200 mg / kg ) or 5 LO ( Zileuton , 80 mg / Kg ) antagonists . ^^^ We also determined protein permeability of cultured glomerular endothelial cells ( which possess no 5 LO ) by measuring their permeability to radiolabeled albumin with and without FLAP antagonists . ^^^ Inhibition of FLAP ( but not inhibition of 5 LO ) reduced proteinuria , with no effect on estimated glomerular filtration rate . ^^^ CONCLUSIONS : These results suggest a role for FLAP other than the activation of 5 LO , possibly in protein handling , and point to FLAP antagonists as anti proteinuric agents . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Inhibition of 5 LO activating protein ( FLAP ) activity decreases proteinuria in streptozotocin ( STZ ) induced diabetic rats . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
These genes include annexin 1 , annexin 2 , COX 2 , cyclooxygenase 1 ( COX 1 ) and cytosolic phospholipase A ( 2 ) ( cPLA ( 2 ) ) , 5 lipoxygenase ( 5 LOX ) , 5 lipoxygenase activating protein ( FLAP ) and 12 lipoxygenase ( 12 LOX ) ( not included in the array data ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Specific cellular immunocytochemical techniques were used to detect the cysteinyl leukotriene synthetic proteins , namely 5 lipoxygenase ( 5 LO ) , 5 lipoxygenase activating protein ( FLAP ) and leukotriene C 4 synthase ( LTC4S ) . ^^^ RESULTS : 5 LO , FLAP and LTC4S , and the CysLT 1 and CysLT 2 receptors were expressed in the majority of eosinophils and in subsets of mast cells and mononuclear cells . 5 LO , FLAP and the CysLT 1 receptor , but not LTC4S or the CysLT 2 receptor , were expressed in a subset of nasal neutrophils . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : The binding of 5 lipoxygenase ( 5 LO ) to 5 LO activating protein ( FLAP ) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid . ^^^ In these cells , FLAP immunoreactivity co localized with that of 5 LO , and was restricted to nuclear envelope . ^^^ Although 5 LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT PCR , Western blot revealed only FLAP and no 5 LO protein . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Here we review a possible role for the 5 lipoxygenase ( 5 LOX ) pathway . 5 LOX is an enzyme that , in association with 5 LOX activating protein ( FLAP ) , leads to the synthesis of leukotrienes from omega 6 arachidonic acid . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : To explore the modulation of 5 lipoxygenase activating protein ( FLAP ) and 5 lipoxygenase ( 5 LOX ) expression in human osteoarthritic ( OA ) chondrocytes , their relative implications in leukotriene B ( 4 ) ( LTB ( 4 ) ) production , the effect of different factors on this system , and the influence of increased LTB ( 4 ) production on the synthesis of catabolic factors of cartilage . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Few studies have investigated the role of polymorphisms in the ALOX5AP gene , encoding 5 lipoxygenase activating protein ( FLAP ) , and asthma . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members , corresponding to the six families of microsomal glutathione transferases ( MGST ) 1 , 2 and 3 , leukotriene C 4 synthase ( LTC 4 ) , 5 lipoxygenase activating protein ( FLAP ) , and prostaglandin E synthase . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We have recently demonstrated that 5 lipoxygenase ( 5 LO ) and its accessory protein , 5 LO activating protein ( FLAP ) , are essential for the survival of Kupffer cells in culture , as their inhibition drives these liver resident macrophages to programmed cell death . ^^^ The FLAP inhibitor reduced leukotriene ( LT ) B ( 4 ) and cysteinyl LT levels and down regulated 5 LO and FLAP protein expression in the liver . ^^^ These findings support the concept that modulation of the 5 LO pathway by FLAP inhibition may be useful in the prevention of hepatotoxin induced necro inflammatory injury . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
FLAP ( 5 lipoxygenase activating protein ) is a nuclear transmembrane protein involved in the biosynthesis of LTs ( leukotrienes ) and other 5 LO ( 5 lipoxygenase ) products . ^^^ First , the 5 LO substrate AA ( arachidonic acid ) concomitantly disrupted the FLAP dimer ( at > or =10 microM ) and inhibited LT biosynthesis . ^^^ Secondly , using Sf 9 cells expressing active and inactive FLAP mutants and 5 LO , we observed that the FLAP mutants capable of supporting 5 LO product biosynthesis also form the FLAP dimer , whereas inactive FLAP mutants do not . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The astrocyte P2X7 evoked rise of CysLT efflux was abolished in the presence of MK 886 , an inhibitor of 5 lipoxygenase activating protein ( FLAP ) whose expression , along with that of 5 lipoxygenase ( 5 LO ) was reported by Northern Blot analysis . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Interestingly , t 10 , c 12 CLA reduced the expression of five lipoxygenase activating protein ( FLAP ) but not the 5 lipoxygenase enzyme . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Importantly , experiments with the 5 LO activating protein inhibitor MK 0591 and the intracellular Ca2+ chelator BAPTA AM demonstrated that the AA regulated 5 LO translocation is FLAP and Ca2+ dependent . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Lipoxygenase ( ALOX 5 ) and FLAP ( ALOX5AP ) gene polymorphisms as factors in vascular pathology and Alzheimer ' s disease . ^^^ However , additional important new data lead us to hypothesize that genetic variability not only in the 5 LOX gene , i . e . , ALOX 5 , but also in polymorphism of the five lipoxygenase activating protein ( FLAP ) gene , i . e . , ALOX5AP , may be associated with Alzheimer ' s pathology . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Aberrant expression of 5 lipoxygenase activating protein ( 5 LOXAP ) has prognostic and survival significance in patients with breast cancer . 5 lipoxygenase ( 5 LOX ) activating protein , 5 LOXAP also known as LOX5AP or FLAP , is a protein that works closely with 5 LOX in regulating the metabolism of arachidonate . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Leukotrienes are produced by 5 lipoxygenase co operating with five lipoxygenase activating protein ( FLAP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
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 . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Antibodies against the following enzymes were also used : cyclo oxygenase ( COX 1 , COX 2 ) , 5 lipoxygenase ( 5 LO ) , 5 lipoxygenase activating factor ( FLAP ) , LTA 4 hydrolase ( LTA4h ) and LTC 4 synthase ( LTC4s ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Here we report that mRNA levels for the three key proteins in LTB 4 biosynthesis , namely 5 lipoxygenase ( 5 LO ) , 5 LO activating protein ( FLAP ) , and LTA 4 hydrolase ( LTA4H ) , are significantly increased in human atherosclerotic plaque ( n = 72 ) as compared with healthy controls ( n = 6 ) . ^^^ Immunohistochemical staining revealed abundant expression of 5 LO , FLAP , and LTA4H protein , colocalizing in macrophages of intimal lesions . ^^^ Furthermore , expression of 5 LO and LTA4H , but not FLAP , is increased in patients with recent or ongoing symptoms of plaque instability , and medication with warfarin correlates with increased levels of FLAP mRNA . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Therefore , the leukotriene biosynthesis inhibitory effect of knipholone was evident by its ability either to inhibit the 5 lipoxygenase activating protein ( FLAP ) or as a competitive ( non redox ) inhibitor of the enzyme . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
RESULTS : These techniques revealed that human bronchial fibroblasts from both subject groups constitutively express 5 lipoxygenase , its activating protein FLAP , the terminal enzymes leukotriene A 4 hydrolase and leukotriene C 4 synthase , and receptors for leukotriene B 4 ( BLT 1 ) and cysteinyl leukotrienes ( CysLT 1 ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
We also demonstrate that the expression of both the MK 886 binding protein and 5 lipoxygenase is necessary for leukotriene synthesis in intact cells . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
The single base extension method was used to genotype SNPs in 5 lipoxygenase ( ALOX 5 , 1708G > A , 21C > T , 270G > A , 1728G > A ) , ALOX 5 activating protein ( ALOX5AP , 218A > G ) , prostaglandin endoperoxide synthase 2 ( PTGS 2 , COX 2 , 162C > G , 10T > G , R228H , V511A ) , LTC4S ( 444A > C ) , and CYSLTR 1 ( 927T > C ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND AND PURPOSE : Recent evidence has implicated the genes for 5 lipoxygenase activating protein ( ALOX5AP ) and phosphodiesterase 4D ( PDE4D ) as susceptibility genes for stroke in the Icelandic population . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Four new susceptibility genes have been identified using genome wide association studies or genome wide linkage studies : LTA ( encoding cytokine lymphotoxin alpha ) on 6p21 . 3 for MI ; LGALS 2 ( encoding galectin 2 , an LTA interacting protein ) on 22q12 q 13 for MI ; ALOX5AP ( encoding 5 lipoxygenase activating protein involved in synthesizing potent pro inflammatory leukotrienes ) on 13q12 13 for MI and stroke ; and PDE4D ( encoding phosphodiesterase 4D ) on 5q12 for ischemic stroke . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : Recently , the 5 lipoxygenase activating protein gene ( ALOX5AP ) was reported to confer a risk of myocardial infarction ( MI ) and stroke , independent of conventional risk factors . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke : phosphodiesterase 4D ( PDE4D ) and 5 lipoxygenase activating protein ( ALOX5AP ) . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
A polymorphism study that examined nine single nucleotide polymorphisms of five leukotriene related genes [ ALOX 5 ( encoding 5 lipoxygenase ) , ALOX5AP ( 5 lipoxygenase activating protein ) , PTGS 2 ( cyclooxygenase 2 ) , LTC4S ( leukotriene C 4 synthase ) , and CYSLTR 1 ( cysteinyl leukotriene receptor 1 ) ] found that promoter polymorphisms of ALOX 5 ( 1708A > G ) and CYSLTR 1 ( 634C > T ) were significantly different between aspirin intolerant asthma and aspirin induced urticaria / angioedema , suggesting different contributions to the lipoxygenase pathway . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
BACKGROUND : 5 Lipooxygenase ( ALOX 5 ) and 5 lipoxygenase activating protein ( ALOX5AP ) are known as key enzymes in cysteinyl leukotriene ( cys LT ) production , critical mediators in aspirin acetylsalicyclic acid ( ASA ) intolerant asthma ( AIA ) . ^^^ METHODS : To understand the pathological process that arises from cys LT overproduction in AIA , we genotyped ALOX 5 Sp1 and ALOX5AP poly ( A ) repeat promoter polymorphism by fluorescent based capillary electrophoresis in the Korean population . ^^^ RESULTS : No significant differences in allele and genotype frequencies of the ALOX 5 and ALOX5AP promoter polymorphisms were observed between the three groups . ^^^ CONCLUSION : Although the alleles of the ALOX 5 and ALOX5AP promoter can not be considered as a prominent risk factor in the development of AIA , the genetic variant of tandem repeat ( GGGCGG ; Sp 1 binding motif ) in ALOX 5 promoter is associated with the severity of airway hyperresponsiveness in AIA patients . . ^^^ |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: P20292 and P09917 |
Pubmed |
SVM Score :0.0 |
NA |
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