Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat renal mesangial cells possess morphological and functional features of smooth muscle cells in culture, such as intracellular myosin filaments, A II receptors and a contractile response to A II. Furthermore, they represent the main glomerular site of PGE2 synthesis. In the presence of A II (50 nM), their PGE2 production rate was significantly increased, this effect being potentiated by arachidonic acid (3 micrograms/ml). After a prior inhibition of arachidonic acid metabolism by cyclooxygenase inhibitors (indomethacin 1 microM or naproxen 0.02 microM) or by a cyclo- and lipoxygenase inhibitor (phenidone 670 microM), the percentage of cells contracting in response to various A II concentrations (10 pM to 10 nM) was significantly enhanced as compared to the basal conditions. On the contrary, the percentage of cells presenting a contractile response to A II in the presence of exogenous PGE2 (50 ng/ml) or of arachidonic acid (3 micrograms/ml) was significantly decreased. These modifications were not related to some changes in the A II receptor properties of the cells, i.e. the number of receptor sites and their affinity constant. The data demonstrate that the contractile response of glomerular mesangial cells is modulated by the PGE2 content of their incubation medium. Since their own PGE2 production rate is enhanced in the presence of A II, this cellular response may represent a local regulatory mechanism of their contractile properties.
Mol Cell Endocrinol 1986 Sep
PMID:Glomerular mesangial cell contractility in vitro is controlled by an angiotensin-prostaglandin balance. 309 26

Circulatory blood corpuscles have enzymes catalyzing arachidonic acid. Platelets have cyclo-oxygenase system which produce highly vasoconstrictive and thrombogenic thromboxane A2 (TXA2). Neutrophils have another type of arachidonate metabolism system, lipoxygenase enzymes, which produce hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT), mediating inflammatory reactions. These arachidonate metabolites were found to play important roles in the evolution of myocardial ischemia. Thromboxane B2 (TXB2) a stable metabolite of TXA2, was elevated in peripheral blood of patients with angina pectoris. This elevation of TXB2 was supposed to be derived from platelet activation in coronary circulation due to altered production of TXA2 and prostacyclin (PGI2). Augmentation of TXA2 was also observed in patients with acute myocardial infarction. TXA2 synthetase inhibitors decreased plasma levels of TXB2 in these patients accompanied by attenuation of infarct size. Neutrophils were found to accumulate in ischemic myocardium and were augmented at reperfusion phase especially at interface between infarcted and risk zone. These infiltrated neutrophils may also provide deleterious effects on myocardial cells by producing lipoxygenase metabolites. In fact, a chemotactic and vasoconstrictive lipoxygenase product, 12-HETE, was produced selectively in ischemic myocardial tissue of an occlusion-reperfusion model. During evolution of myocardial cell damage, platelets and neutrophils, accumulated in ischemic tissue, may contribute to the exacerbation of microcirculatory disorders by producing vasoactive prostanoids, leading to expansion of myocardial necrosis. We should gain insights into these cellular interactions through arachidonate metabolism under normal and catastrophic conditions of coronary circulation.
J Mol Cell Cardiol 1988 Mar
PMID:Arachidonate metabolism in myocardial ischemia and reperfusion. 313 47

A near full-length cDNA for a pea (Pisum sativum) seed lipoxygenase was isolated and sequenced. It has a protein coding sequence (2583 bp), 5' (59 bp) and 3' (191 bp) non-coding regions, and a poly(A) tail (20 bp). The predicted amino acid sequence indicates a polypeptide of Mr 97,628 that shows about 86% amino acid identity with a soya-bean lipoxygenase 3 protein sequence [Yenofsky, Fine & Liu (1988) Mol. Gen. Genet. 211, 215-222]. The cDNA directs the transcription of mRNA that can be translated to give an anti-lipoxygenase-precipitable polypeptide in vitro.
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PMID:The complete amino acid sequence of a pea (Pisum sativum) seed lipoxygenase predicted from a near full-length cDNA. 314 Jul 91

Prostaglandin-H-synthase (PHS) peroxidase has been suggested to mediate drug metabolism particularly in extrahepatic tissues low in monooxygenase (MFO) activity. PHS can oxidize various xenobiotics in vitro; its contribution in vivo is still uncertain and is currently assessed by differences in the MFO- and PHS-catalyzed product/adduct formation of a few suitable substrates. Cells in culture that are PHS competent but MFO deficient can provide an additional approach for further investigating the role of PHS in the metabolic activation of foreign compounds. To this end, a cell line has been derived from ram seminal vesicles (SEMV), a tissue known as a good source of PHS but shown to be devoid of MFO activity. SEMV cells can be cultured in IBR or in RPMI medium supplemented with fetal calf serum, and have been subcultured until passage 30. The arachidonic acid (AA) metabolism in these cells has been characterized: besides incorporation in the lipid pool, AA was mainly metabolized to prostaglandin (PG) E2; minor products were PGF2 alpha and the lipoxygenase products 12- and 15-HETE. The PGE2 production (17 nmol/10(6) cells.24 h) of SEMV cells (passage 10) exceeded at least 10-fold that of other cells cultured under similar conditions. These data, indicative of high PHS activity, suggest that the cells can be a useful tool for future studies on the objectives outlined above.
Mol Toxicol
PMID:Prostaglandin-H-synthase competent cells derived from ram seminal vesicles: a tool for studying cooxidation of xenobiotics. 315 3

In this paper it was examined whether it could reproduce "in vitro", some of the myocardial dysfunction see "in vivo" in autoimmune myocarditis. The isolated atria from mice hyperimmunized with heart exhibited a lymphomononuclear cell infiltration and alteration in contractility: dysrhythmia and decrease in tension. These alterations highly resembled that triggered by spleen lymphocytes from autoimmune myocarditis mice, when they reacted with normal atria. This effect appears to be specific since cells sensitized to an irrelevant antigen were inactive, and was not secondary to allogenic interaction. The free-cell supernatant of autoimmune cells was inactive, point out the requirement of lymphocyte-heart contact. The most likely effectors of lymphocytes-induced alteration of atria contractility were T-lymphocytes. Beta-lymphocyte subset had no effect. Inhibitors of lipoxygenase(s) pathway of arachidonic acid metabolism, inhibited induced alterations of contractility and the SRS-A receptor blocker, FPL-55712 improved cardiac function. In addition LTC4 release was increased either in autoimmune myocarditis hearts and in normal hearts challenged with autoimmune cells; the hearts proving to be responsible of leukotriene synthesis. Normal or immune cells alone failed to release LTC4. Lipoxygenase(s) inhibitors diminished LTC4 release while indomethacin could not reverse the effect. It is concluded that mononuclear cells infiltrates occurring in hearts with autoimmune myocarditis mice are related to cardiac impairment, being critical in the myocardial dysfunction etiology. The way suggested for these phenomena to take place is, at least in part, the harmful effect of SRS-A released by hearts when specific antigens of myocardial tissue are recognized by autoimmune cells.
J Mol Cell Cardiol 1988 Feb
PMID:Lymphocytes infiltration induces dysfunction in autoimmune myocarditis: role of SRS-A. 326 Sep 62

Cardiac muscle cell injury may be related to metabolic changes associated with a rise in intracellular calcium. The mechanisms by which an elevated Ca2+ can cause injury are uncertain, but injury could occur by activation of any one or several calcium-dependent processes. To examine whether the process is mediated by prostaglandins (PG) or leukotriens (LT), we measured the successive release of creatine kinase (CK), PGE2 and LTC4 that have been reported to induce the cell injury via the arachidonic acid cascade, to the culture medium from myocardial cells under hypoxic or aerobic conditions. CK release, a biochemical marker of muscle cell necrosis, was first detected in the medium of hypoxic cultures at 9 h. Both PGE2 and LTC4 production and release were delayed, being first detected at 12 h after initiating hypoxia treatment. Addition of exogenous PGE2 or LTC4 to the culture medium (1.0 or 10 ng/ml) did not cause any effect on the CK release under aerobic condition. Cyclooxygenase inhibitor, indomethacin (1 X 10(-5) M) or lipoxygenase inhibitor, AA861 (1 X 10(-5) M), reduced the synthesis of PGE2 by 80% or LTC4 by 68% under hypoxia, respectively, but caused no beneficial effect on the CK release. These findings suggest that cardiac muscle cells themselves produce PGE2 and LTC4 after hypoxia and that the production of these compounds merely occurs as a result, but not as a cause of cell injury.
J Mol Cell Cardiol 1987 Jun
PMID:Stimulated synthesis of prostaglandin E2 or leukotrien C4 from myocardial cells is not a cause but a result of their injury under hypoxia. 347 55

Arachidonate 5-lipoxygenase of rat basophilic leukemia (RBL-1) cells was purified more than 1000-fold by gel filtration and anion exchange protein-high performance liquid chromatography (HPLC). Physical properties of the purified 5-lipoxygenase such as molecular weight (74,000-76,000), N-terminal sequence (30 amino acids), and amino acid composition were determined. The purified enzyme converted [14C]arachidonic acid at 20 degrees to [14C] 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and to [14C]dihydroxyeicosatetraenoic acids (diHETEs). Utilizing [14C] 5(S)HPETE as substrate, the purified enzyme also converted the hydroperoxy acid to [14C]diHETES. The [14C]diHETE reaction products were identified primarily (greater than 80% of recovered radioactivity) as the nonenzymatic hydrolysis products of leukotriene A4 (i.e., 6-trans-leukotriene B4 and 12-epi-6-trans-leukotriene B4) by reverse phase HPLC, scanning spectrophotometry, and gas chromatography-mass spectrometry. The bioconversion of [14C] arachidonate and [14C]5(S)HPETE to reaction products by the purified enzyme was dependent on the presence of both Ca2+ and ATP. The enzymatic activities were inhibited in a similar manner by the lipoxygenase inhibitors nordihydroguaiaretic acid, diphenyldisulfide, and SK&F 86002. The data provide evidence that RBL-1 cell 5-lipoxygenase and leukotriene A4 synthetase activities reside on a single monomeric protein with a free N-terminus and that they possess similar biochemical characteristics.
Mol Pharmacol 1986 Dec
PMID:Purification, characterization, and structural properties of a single protein from rat basophilic leukemia (RBL-1) cells possessing 5-lipoxygenase and leukotriene A4 synthetase activities. 378 38

The effects of melittin on the synthesis of lipoxygenase metabolites of arachidonic acid in human leukocytes and platelets were studied using high performance liquid chromatography. Melittin was found to stimulate strongly the formation of leukotrienes and hydroxy-eicosatetraenoic acids (HETEs) in a concentration-dependent fashion. The metabolites detected were LTB4, omega-OH-LTB4, omega-COOH-LTB4, LTC4, 5-HETE, 12-HETE, 15-HETE, 5S,12S-DiHETE, and 5S,15S-DiHETE. These results suggest that the action of melittin on the formation of arachidonic acid metabolites might be involved in its ability to release endogenous substrates required for the synthesis of 5-, 15-, and 12-lipoxygenase products in leukocytes and platelets, respectively.
Mol Pharmacol 1985 Dec
PMID:Stimulation of lipoxygenase product synthesis in human leukocytes and platelets by melittin. 393 9

We investigated whether the mitogenic response induced by local mast-cell secretion in the rat mesentery was affected by suppression of phospholipase A2, lipoxygenase, or cyclooxygenase in arachidonic acid metabolism. Enzyme inhibitor was given in a single intravenous dose 5 min before intraperitoneal injection of the mast-cell secretagogue 48/80. Mepacrine, a phospholipase A2 inhibitor, suppressed the generation of both leukotrienes (SRS) and prostaglandins (PG), whereas the lipoxygenase inhibitor BW 755C reduced the generation of SRS, and the cyclooxygenase inhibitor indomethacin significantly suppressed the generation of PG. None of the enzyme inhibitors affected the basal mesenteric histamine content or histamine release in the mesentery after exposure to 48/80, and none of them affected mast-cell-mediated mitogenesis in the mesentery as judged by specific DNA activity and mitosis counting. The stimulation of DNA synthesis and mitosis initiated by secreting mast cells is apparently not mediated or modulated by synthesis of leukotrienes, prostaglandins, or other known arachidonic acid metabolites.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:On the role of arachidonic acid metabolites in mast-cell mediated mitogenesis in the rat. 614 31

Administration of leukotrienes to cardiac tissue produces contractile depression and coronary artery constriction [5,8], thus making it possible that these substances mediate cardiac dysfunction under pathologic conditions. Up to now no studies have been performed to determine whether cardiac tissue has the inherent ability to produce leukotrienes. The present study was therefore carried out to ascertain whether isolated hearts perfused with saline buffer devoid of any blood constituents can produce leukotrienes under a variety of pharmacologic and pathologic situations. No leukotriene (LT) C4 was detected under control conditions or from hearts subjected to global ischemia and reperfusion or hypoxia and reoxygenation. A23187, a Ca2+ ionophore markedly stimulated LTC4 release. This effect was prevented by nordihydroguaiaretic acid, a selective lipoxygenase inhibitor. The addition of arachidonate as substrate had no effect on LTC4 release. In an attempt to divert arachidonate to LTC4 production, indomethacin, a cyclo-oxygenase inhibitor was added before arachidonate. No LTC4-like immunoreactivity was found in these experiments. These studies suggest that a lipoxygenase pathway for leukotriene production is present either in the coronary vasculature or myocardium. It was stimulated only by Ca2+ ionophore, probably indicating a requirement for high amounts of intracellular Ca2+.
J Mol Cell Cardiol 1984 Nov
PMID:Calcium-ionophore stimulated release of leukotriene C4-like immunoreactive material from cardiac tissue. 644 Sep 98


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