Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that glutamate exerts a stimulatory action on somatostatin secretion in cortical neurons essentially through NMDA receptor sites. Here, we investigated whether arachidonic acid release could be modified after NMDA receptor activation in cortical neurons in primary culture. We also studied whether pharmacological manipulation of phospholipase A2 could modify somatostatin release. We found that both glutamate and NMDA (N-methyl-D-aspartate) stimulated [3H]arachidonic acid release. NMDA-evoked arachidonic acid release was inhibited by MK-801 and TCP (two NMDA receptor-type antagonists), or by mepacrine, an inhibitor of phospholipase A2. NMDA-induced somatostatin release was inhibited by MK-801, mepacrine and by another phospholipase A2 inhibitor, p-bromophenacylbromide (pBPB). However, responses to NMDA were unaffected by H7, NDGA (nordihydroguaiaretic acid), indomethacin or by RHC 80267 (inhibitors of protein kinase C, lipooxygenase, cyclooxygenase and diacylglycerol lipase, respectively). Mepacrine (greater than or equal to 100 microM) decreased NMDA-stimulated phosphatidylinositol (PI) hydrolysis and at higher concentrations (250 microM) was also able to inhibit basal release whereas pBPB had no effect in the range of concentrations tested. Neomycin (which inhibits phosphatidylinositol metabolism by binding strongly and selectively to inositol phospholipids) reduced by 30% the NMDA-stimulated somatostatin release, although chronic treatment of neurons with the phorbol ester 12-myristate, 13-acetate (PMA) had no effect on this response. Melittin, an activator of phospholipase A2, was able to stimulate both arachidonic acid release and somatostatin secretion. High-performance liquid chromatography (HPLC) analysis of tritiated metabolites released from cortical neurons under basal or NMDA-stimulated conditions revealed that [3H]arachidonic acid was the only metabolite detectable. Furthermore, external addition of arachidonic acid increased somatostatin secretion. Our results show a correlation between the two parameters studied.
...
PMID:NMDA receptor activation stimulates phospholipase A2 and somatostatin release from rat cortical neurons in primary cultures. 135 46

In cultured rat aorta-derived A-10 cells, epidermal growth factor-urogastrone (EGF-URO) acts synergistically with arginine vasopressin (AVP) to augment the AVP-mediated release of 3H-arachidonate (3H-AA) from 3H-AA prelabeled cells. On its own, EGF-URO had no effect on AA release and had no effect on calcium influx or efflux either in the absence or presence of AVP. The synergistic action of EGF-URO was not affected by actinomycin D, cycloheximide, indomethacin, by the diacylglycerol lipase inhibitor U-57,908, or by the tyrosine kinase inhibitors genistein (GS) and tyrphostin (TP). TP did, nonetheless, completely abrogate 3H-thymidine incorporation triggered in the presence of EGF-URO. Although EGF-URO stimulated an increase in calpactin-II (lipocortin-I) phosphorylation in permeabilized cells, no such increase was detected in intact cells exposed to EGF-URO either alone or in combination with AVP, under conditions where EGF-URO augmented the action of AVP. The phospholipase A2 inhibitor, mepacrine, had no effect on AVP-mediated AA release, but abolished the synergistic action of EGF-URO. We conclude that in contrast with our previous results with gastric smooth muscle strips, wherein EGF-URO acts via the diacylglycerol lipase-mediated metabolism of diacylglycerol, and in keeping with observations with cultured mesangial cells, EGF-URO acts synergistically with AVP in A-10 cells via the activation of phospholipase A2. This synergistic action of EGF-URO does not appear to be due to increased levels of cyclooxygenase and would appear not to require increased tyrosine kinase activity.
...
PMID:Synergistic actions of epidermal growth factor-urogastrone and vasopressin in cultured aortic A-10 smooth muscle cells. 138 68

Influence of arachidonate metabolite pathway on adipose differentiation was investigated using primary culture of adipocyte precursors in defined medium. Treatment of the cells with cyclooxygenase inhibitors stimulates adipose differentiation by at least 2-fold. Among the various arachidonate metabolites tested, only prostaglandin F2 alpha (PGF2 alpha) was found to inhibit the differentiation of adipocyte precursors in a dose dependent fashion. Other eicosanoids tested did not have any effect. A 50% inhibition of adipose differentiation was observed with a dose of PGF2 alpha of 3 x 10(-9)M to 7 x 10(-9)M according to the strain of rats used. Maximal inhibition occurred at PGF2 alpha concentrations equal or higher than 10(-8)M. PGF2 alpha inhibited not only the expression of late markers of adipose differentiation such as G3PDH and triglycerides accumulation but also the mRNA expression of early markers of adipose differentiation such as clone 154, lipoprotein lipase and ap2 gene. These results indicate that PGF2 alpha represents a physiological negative modulator of adipose differentiation.
...
PMID:Prostaglandin F2 alpha inhibits the differentiation of adipocyte precursors in primary culture. 155 May 52

In pancreatic islets the bulk of phosphoinositide-specific phospholipase C (PI-PLC) activity was cytosolic. The soluble enzyme was activated by submicromolar concentrations of Ca2+, independent of calmodulin. It was unaffected by glucose and a series of glycolytic intermediates, including glyceraldehyde 3-phosphate. These observations lend support to the hypothesis that glucose-stimulated inositol triphosphate production in islets may be secondary to and provoked by glucose-mediated Ca2+ influx. All four pyridine nucleotides stimulated PI-PLC. Phosphatidylinositol hydrolysis was also stimulated by dioleine and arachidonic acid, and by the polyamines, putrescine and spermine. Phosphatidylinositol hydrolysis was inhibited by chlorpromazine, tetracaine, ATP, 5'-AMP, inorganic pyrophosphate and by phosphatidylinositol 4,5-bisphosphate, phosphatidylcholine and phosphatidylserine--but not affected by phosphatidylethanolamine. The cyclic nucleotides, cAMP and cGMP had no effect on the enzyme, and GTP-gamma-S did not activate the enzyme event at very low Ca2+ concentrations. The diglyceride lipase inhibitor, RHC 80267, and the cyclooxygenase inhibitor, indomethacin, had no effect on PI-PLC activity.
...
PMID:Characteristics of phosphoinositide-specific phospholipase C activity from mouse pancreatic islets. 166 77

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.
...
PMID:Prostaglandin and thromboxane biosynthesis. 190 23

Human fibroblasts and mouse C3H 10T1/2 cells in culture were prelabeled with [3H]arachidonic acid and exposed to UVA radiation. Cells released labeled arachidonate metabolites into medium in a dose-dependent fashion (5-20 J cm-2). The time course of release appeared biphasic with peak responses occurring immediately and at 2 h post irradiation. Release of radiolabel was oxygen and calcium ion dependent and was inhibited by the addition of phenylglyoxal, indomethacin, and dibucaine to the medium. High performance liquid chromatographic examination of medium extracts revealed UVA stimulation of cyclooxygenase metabolism of [3H]arachidonic acid and specifically, prostaglandin E2 production by cells in culture. Furthermore, UVA stimulated a dose-dependent release of membrane incorporated [3H]choline from cells in culture. Paper chromatographic analysis of the medium provided evidence that choline release from the membrane was predominantly accompanied by release of phosphorylcholine with some glycerophosphorylcholine suggesting indirectly that the major pathway for UVA-stimulated arachidonic acid release was via phospholipase C and diacylglycerol lipase enzyme systems.
...
PMID:Long wave ultraviolet radiation stimulates arachidonic acid release and cyclooxygenase activity in mammalian cells in culture. 249 14

Tritiated arachidonic acid (3H-AA)-labeled rat synovial fibroblasts stimulated with human recombinant interleukin-1 beta (rIL-1 beta) released incorporated radiolabel in a time-dependent and dose-dependent manner, with labeled prostaglandins representing 29% of the released radiolabel. Treatment of the cells with dibutyryl cAMP or prostaglandin E2 enhanced both spontaneous and rIL-1 beta-induced 3H-AA release; treatment with indomethacin or naproxen inhibited the response. The effects of these cyclooxygenase inhibitors on 3H-AA release were not reversed by the addition of prostaglandin E2. The activities of phospholipase A, phospholipase C, and diglyceride lipase were detected in the homogenates of rat synovial fibroblasts. Pretreatment of synovial cells with rIL-1 beta resulted in a threefold stimulation of phospholipase A activity and a slight increase in phospholipase C activity in cell homogenates. These data show that rIL-1 beta stimulates phospholipase activities in rat synovial fibroblasts and that at least one of these activities may be regulated by either prostaglandins or cAMP.
...
PMID:Interleukin-1 stimulation of phospholipase activity in rat synovial fibroblasts. Possible regulation by cyclooxygenase products. 284 61

The relative importance of several phospholipid pathways in cyclic AMP (cAMP) metabolism and growth hormone (GH) release was determined by an indirect, pharmacological approach in cultured anterior pituitary cells. The diglyceride lipase inhibitor RHC-80267 (30-100 microM) had no significant effect on cAMP levels but markedly inhibited basal and growth hormone-releasing factor-(GRF) stimulated GH secretion. A phospholipase A2 inhibitor quinacrine (30 microM) increased cellular cAMP content while decreasing GH release. Indomethacin, which reduces cyclooxygenase activity, affected neither cAMP levels nor GRF-enhanced GH release; this drug (30-100 microM) did reduce basal GH release. The lipoxygenase inhibitors nordihydroguaiaretic acid and BW-755c both reduced basal and GRF-stimulated GH release in a concentration-dependent manner. Both agents had various effects on cAMP levels. These results suggest that phospholipid metabolism, through both the cyclooxygenase and lipoxygenase pathways, contributes to basal GH release, while the lipoxygenase route predominates in GRF-stimulated GH release in vitro. Interestingly, cAMP metabolism can be dissociated from GH release with some of these probes, indicating an action of phospholipid metabolites distal or lateral to the cAMP-generating system.
...
PMID:Modification of basal and GRF-stimulated cyclic AMP levels and growth hormone release by phospholipid metabolic enzyme inhibitors. 298 27

It has been postulated that the diacylglycerol lipase pathway is a predominant source of the free arachidonic acid which is released from phospholipids upon the exposure of human platelets to thrombin. The amount of released arachidonic acid and other fatty acids in thrombin-stimulated platelets was determined in the presence of BW755C, the cyclooxygenase/lipoxygenase inhibitor, and in relation to phosphatidylinositol degradation and phosphatidic acid formation. A stearic acid:arachidonic acid molar ratio approaching unity would be expected in the free fatty acid fraction if the latter pathway were a major source of released arachidonic acid. Our results indicate that the diacylglycerol lipase pathway contributes a maximum of 3-4 nmol of arachidonic acid/2 X 10(9) platelets or 12-15% of the total arachidonic acid released (25.8 nmol/2 X 10(9) platelets) upon exposure to thrombin (2 units/ml) for 4 min. Trifluoperazine inhibited most of the thrombin-dependent free arachidonic acid release but only 15% of the absolute loss of arachidonic acid from phosphatidylinositol. Therefore, we conclude that the diacylglycerol lipase pathway represents only a minor source of the free arachidonic acid that is released upon thrombin stimulation of human platelets.
...
PMID:Diacylglycerol lipase pathway is a minor source of released arachidonic acid in thrombin-stimulated human platelets. 308 Oct 1

Various stimuli act on polymorphonuclear leukocytes (PMN), activating membrane-bound phospholipase A2 and C, and diglyceride lipase and then liberating unsaturated fatty acids (USFAs). These liberated USFAs are immediately metabolized through various metabolic pathways such as cyclooxygenase, lipoxygenase, phosphatidylinositol metabolism etc. It is possible that the metabolic intermediates of these pathways reveal various physiological actions. This work was undertaken to clarify whether stimuli on PMN depend on these USFAs themselves or on their oxidation products. The following results were obtained: 1. USFAs such as arachidonate and linoleate stimulate PMN, accelerating superoxide (O2) generation, depolarization of membrane potential and increase in [Ca2+]i. 2. Oxidation products of USFAs have no stimulative effect on PMN. The decrease in the stimulative effect of these USFAs following their oxidation is proportional to the quantitative decrease in non-oxidized linoleate. 3. USFAs accelerate membrane permeability of Ca2+, and their oxidation products enhance non-specific membrane permeability in proportion to the formation of monohydroxy compound. These results suggest that stimulative effects of USFAs on PMN do not depend on their oxidation products but on unoxidized fatty acids. Furthermore, among the oxidation products of the USFAs, monohydroxy compound acts as a strong perturber of membrane and accelerates membrane permeability.
...
PMID:Metabolic response of polymorphonuclear leukocyte to arachidonic and linoleic acids. 310 Oct 75


1 2 3 4 5 Next >>

---