Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cultured dorsal root ganglion (DRG) neurons prelabeled with [3H]arachidonic acid [( 3H]AA), bradykinin (BK) stimulation resulted in increased levels of radioactive diacylglycerol, monoacylglycerol, and free AA. The transient increases in content of radioactive diacylglycerol and monoacylglycerol preceded the increase in level of free AA, suggesting the contribution of a diacylglycerol lipase pathway to AA release. An analysis of the molecular species of diacylglycerols in unstimulated cultures revealed the presence of two primary [3H]AA-containing species, 1-palmitoyl-2-arachidonoyl and 1-stearoyl-2-arachidonoyl diacylglycerol. BK stimulation resulted in a preferential increase in content of 1-stearoyl-2-arachidonoyl diacylglycerol. When DRG cultures were labeled with [3H]stearic acid, treatment with BK increased the amount of label in diacylglycerol and free stearic acid, but not in monoacylglycerol. This result suggested that AA release occurred through the successive actions of an sn-1 diacylglycerol lipase and monoacylglycerol lipase. Other data supporting a diacylglycerol lipase pathway was the significant inhibition of [3H]AA release and consequent accumulation of diacylglycerol by RG 80267, which preferentially inhibits diacylglycerol lipase. Analysis of the molecular species profiles of individual phospholipids in DRG neurons indicated that phosphoinositide hydrolysis may account for a significant portion of the rapid increase in content of 1-stearoyl-2-arachidonoyl diacylglycerol. We were unable to obtain evidence that the phospholipase A2 pathway makes a significant contribution to BK-stimulated AA release in DRG cultures. Under our assay conditions there were no BK-stimulated increases in levels of radioactive lysophosphatidylinositol, lysophosphatidylcholine, or lysophosphatidylethanolamine in cultures prelabeled with [3H]inositol, [3H]choline, or [3H]-ethanolamine, respectively.
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PMID:Bradykinin stimulates arachidonic acid release through the sequential actions of an sn-1 diacylglycerol lipase and a monoacylglycerol lipase. 173 88

In order to clarify the relationship between composition and lipolytic responses to lipoprotein lipase (LPL), very low density lipoproteins (VLDL) from rats or humans were incubated with a commercially available LPL or with a partially purified LPL from postheparin human plasma and fatty acids released from VLDL were determined in vitro. VLDL from rats fed a diet containing 0.25% cholesterol for 6 months were rich in cholesterol and poor in triglycerides, and released less fatty acids from incubation with LPL than those from control rats. VLDL from normo-and hypertriglyceridemic human subjects were incubated with LPL. The fatty acid release poorly correlated with the apoprotein ratios of VLDL, apo C-III/C-II, B/E, and C/E with the exception of apo B/C, but it correlated well with the ratio of triglyceride/either one of the surface components including total apoproteins, free cholesterol and phospholipids in VLDL or the ratio of the triglyceride/total sum of the surface components. The correlation coefficients between fatty acid release and a ratio of triglyceride/total surface components were 0.774 (using the commercially available LPL) and 0.786 (using the partially purified human LPL). The fatty acid release increased after pretreatment of VLDL with phospholipase A2. The phospholipid content of VLDL was reduced without significant changes in other VLDL components. Thus, the responses of VLDL to LPL treatment may depend mainly upon the surface: core relationship of VLDL rather than its apoprotein composition except in rare clinical cases such as apo C-II deficiency.
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PMID:Composition of very low density lipoproteins and in vitro effect of lipoprotein lipase. 181 58

Alpha 1-Adrenergic receptors and bradykinin receptors are two distinct membrane receptors that stimulate phospholipid breakdown and arachidonic acid and arachidonic acid metabolite release. In the current studies, we have examined several mechanisms to assess their possible contribution to arachidonic acid release in the Madin-Darby canine kidney cell line by agonist stimulation of these receptors: 1) activation of phospholipase A2 (PLA2); 2) sequential activation of phospholipase C, diacylglycerol lipase, and monoacylglycerol lipase; and 3) inhibition of the sequential action of fatty acyl-CoA synthetase and lysophosphatide acyltransferase. Experiments were conducted to measure the stimulation of lysophospholipid production by epinephrine and bradykinin, the rate of incorporation of [3H]arachidonic acid into stimulated and unstimulated cells, and the effect on [3H]arachidonic acid release of treating cells with exogenous phospholipase C. The data indicate that stimulation of PLA2 activity is regulated by alpha 1-adrenergic and bradykinin receptors and that this stimulation is mediated, at least in part, by the activation of protein kinase C. We find that the role of diacylglycerol in arachidonic acid release is as an activator of protein kinase C and not as a substrate for a lipase. Moreover, the hormonal agonists do not appear to inhibit fatty acid reacylation. Experiments using the Ca2(+)-sensitive dye fura-2 and the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid suggest that bradykinin activates PLA2 by a transient elevation of intracellular Ca2+. This action appears to be less important for activation of PLA2 by epinephrine. Taken together, these data are consistent with the following conclusions. 1) Hormone-stimulated arachidonic acid release in Madin-Darby canine kidney-D1 cells occurs as a consequence of PLA2 activation. 2) The ability of an agonist both to mobilize Ca2+ and to activate protein kinase C contributes to its efficacy as a stimulator of PLA2-mediated arachidonic acid release.
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PMID:Intracellular Ca2+ and protein kinase C interact to regulate alpha 1-adrenergic- and bradykinin receptor-stimulated phospholipase A2 activation in Madin-Darby canine kidney cells. 184 14

We describe the enzymological regulation of the formation of prostaglandin (PG) D2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2 (prostacyclin), and thromboxane (Tx) A2 from arachidonic acid. We discuss the three major steps in prostanoid formation: (a) arachidonate mobilization from monophosphatidylinositol involving phospholipase C, diglyceride lipase, and monoglyceride lipase and from phosphatidylcholine involving phospholipase A2; (b) formation of prostaglandin endoperoxides (PGG2 and PGH2) catalyzed by the cyclooxygenase and peroxidase activities of PGH synthase; and (c) synthesis of PGD2, PGE2, PGF2 alpha, 9 alpha, 11 beta-PGF2, PGI2, and TxA2 from PGH2. We also include information on the roles of aspirin and other nonsteroidal anti-inflammatory drugs, dexamethasone and other anti-inflammatory steroids, platelet-derived growth factor (PDGF), and interleukin-1 in prostaglandin metabolism.
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PMID:Prostaglandin and thromboxane biosynthesis. 190 23

In guinea pig gastric longitudinal muscle preparations, wherein epidermal growth factor-urogastrone (EGF-URO) causes contraction via the generation of arachidonate-derived prostaglandins, the specific diacylglycerol lipase (DG lipase) inhibitor, U57,908 (formerly designated RHC 80267) completely blocked EGF-URO and transforming growth factor-alpha (TGF-alpha)-mediated contraction, without affecting contractions caused by other agonists such as bradykinin, prostaglandin F2 alpha or arachidonic acid (AA). In contrast, the contractile actions of EGF-URO and TGF-alpha on the gastric circular muscle component, present in the same tissue strip as the longitudinal muscle preparation, were unaffected by concentrations of U57,908 that maximally inhibited contraction in the longitudinal muscle preparation. We conclude that in the longitudinal muscle preparation, EGF-URO acts not by the activation of phospholipase A2, but rather via the metabolism of diacylglycerol by DG lipase, thereby liberating arachidonic acid for the synthesis of contractile prostanoids. We also conclude that, even in the same tissue, the effects of EGF-URO on anatomically different components (longitudinal muscle versus circular muscle) can be mediated via two quite distinct signal transduction pathways.
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PMID:Diacylglycerol lipase and the contractile action of epidermal growth factor-urogastrone: evidence for distinct signal pathways in a single strip of gastric smooth muscle. 190 65

Subcellular liver fractions from rats receiving a subcutaneous injection of turpentine, which causes a local inflammation, show an increased synthesis of Prostaglandin E2 and Prostaglandin F2 alpha which reaches a peak 90 minutes and 3 hours after treatment, respectively. Stimulation of phospholipase A2 activity of liver cell preparations seems to be responsible for the supply of arachidonic acid necessary to feed PG synthesis: this stimulation is accompanied by unchanged levels of diacylglycerol lipase, diacylglycerol kinase and protein kinase C activities and by an unchanged content of diacylglycerol in the liver tissue. This picture does not favour the hypothesis of an involvement of phospholipase C in the early stages after turpentine treatment. Determinations of GTP-ase activity in plasma membrane-rich liver preparations give ambiguous results, which do not allow any conclusion on the possible role of G-proteins in phospholipase A2 activation.
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PMID:Rat liver eicosanoid synthesis during turpentine-induced inflammation. 195 99

Nitrogen dioxide (NO2), an environmental oxidant, alters the plasma membrane structure and function of pulmonary artery endothelial cells through peroxidative injury. Because perioxidative injury can activate membrane phospholipases and alter phospholipid composition of membranes, we evaluated the effects of NO2 exposure on phospholipase A1 (PLA1), phospholipase A2 (PLA2), and diacylglycerol lipase (DG lipase) activities in pulmonary artery endothelial cell plasma, mitochondrial, and microsomal membranes. We also evaluated the effect of NO2 exposure on the phospholipid composition of plasma membranes of these cells. Exposure to 5 ppm NO2 for 48 hr resulted in a significant (p less than 0.01) increase in PLA1 activity in plasma membranes but not in mitochondrial or microsomal membranes of pulmonary artery endothelial cells, whereas PLA2 and DG lipase activities were comparable to controls in all membranes. As a result of PLA1 activation, the total phospholipid content of the plasma membranes of NO2-exposed cells was significantly (p less than 0.01) reduced compared to controls. Phosphatidylethanolamine (PE) content was reduced (p less than 0.05), whereas lyso-PE (LPE), a product of PLA1 hydrolysis of PE, as well as phosphatidylserine (PS) contents were increased (p less than 0.01 for both LPE and PS) in the plasma membranes of NO2-exposed cells. Incorporation of exogenous PS into pulmonary artery endothelial cells mimicked the stimulatory effect of NO2 on PLA1 activity. These results demonstrate that NO2 specifically reacts with the plasma membrane component of pulmonary artery endothelial cells, causing specific activation of PLA1. The NO2-induced increase of PS in the plasma membranes appears to be responsible for the specific activation of PLA1 in pulmonary artery endothelial cells.
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PMID:Plasma membrane-specific phospholipase A1 activation by nitrogen dioxide in pulmonary artery endothelial cells. 200 Jun 40

Chromaffin cells from bovine adrenal medulla secrete catecholamines on stimulation with acetylcholine. In addition to the activation of the phosphatidylinositol cycle, arachidonic acid is generated, which was thought to be the result of phospholipase A2 activation. We have demonstrated in isolated plasma membranes of these cells that arachidonic acid is generated by a two-step reaction of diacylglycerol and monoacylglycerol lipase splitting diacylglycerol, which originates from the action of phospholipase C on phosphatidylinositols. No phospholipase A2 activity could be detected in plasma membranes so far. External addition of arachidonic acid increases the release in the absence and in the presence of agonist. Inhibition of the diacylglycerol lipase by RHC 80267 suppresses the catecholamine release, which is restored on addition of arachidonic acid. This effect, however, is reversed by lipoxygenase inhibitors, indicating that it is not arachidonic acid itself, but one of its lipoxygenase products, that is essential for inducing exocytosis.
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PMID:Arachidonic acid liberated by diacylglycerol lipase is essential for the release mechanism in chromaffin cells from bovine adrenal medulla. 210 75

The major functional pool of lipoprotein lipase (LPL) that hydrolyzes triglycerides in circulating lipoproteins is located on the vascular endothelium. The macrophage-secreted cytokine tumor necrosis factor (TNF), a molecule known to affect endothelial cell functions, was used to test the hypothesis that alterations of endothelial cell metabolism regulate the binding of LPL to these cells. TNF addition induced rapid (maximum release at 45 minutes) dissociation of LPL protein and activity from its binding sites on cultured porcine aortic endothelial cells. LPL release by TNF required endothelial cell metabolic event(s) which involved cell secretion. In addition, LPL release was inhibited by pertussis toxin, suggesting the involvement of guanine nucleotide regulatory protein(s). Addition of arachidonic acid, a molecule known to be released by endothelial cells due to phospholipase A2 activation by TNF treatment, released LPL from the cell surface. Furthermore, direct modulation of cellular phospholipase A2 activity also led to changes in the release of LPL. Our studies demonstrate that alterations in the cellular metabolism of endothelial cells, for example, by TNF, may release functional pools of LPL from the vascular endothelium. This decrease in LPL on endothelial cell surfaces might be involved in the development of hypertriglyceridemia and redirection of energy flow during infections and inflammation.
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PMID:Tumor necrosis factor induced release of endothelial cell lipoprotein lipase. 211 95

The relationship between Ca2(+)-dependent arachidonic acid release and exocytosis from digitonin-permeabilized bovine adrenal chromaffin cells was investigated. The phospholipase A2 inhibitors mepacrine, nordihydroguaiaretic acid and indomethacin had no effect on either arachidonic acid release or secretion. The phospholipase A2 activator melittin had no effect on secretion. The specific diacylglycerol lipase inhibitor RG80267 had no effect on secretion, but decreased basal arachidonic acid release to such an extent that the level of arachidonic acid in treated cells in response to 10 microM-Ca2+ was equivalent to that of control cells in the absence of Ca2+. Staurosporine, a protein kinase C inhibitor, was found to abolish Ca2(+)-dependent arachidonic acid release completely, but had only a slight inhibitory effect on Ca2(+)-dependent secretion. It is concluded that arachidonic acid is not essential for Ca2(+)-dependent exocytosis in adrenal chromaffin cells.
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PMID:Relationship between arachidonic acid release and Ca2(+)-dependent exocytosis in digitonin-permeabilized bovine adrenal chromaffin cells. 212 93


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