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

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calphobindins (CPBs) I, II and III which we isolated and characterized from placenta belong to a family of calcium and phospholipid binding proteins represented by lipocortins known to inhibit phospholipase A2(PLA2). The amino acid sequence of three CPBs shares much homology with lipocortins I and II, so we investigated the functions of CPBs in affecting the enzymatic activities of PLA2 and also phospholipase C(PLC). In our experiments CPBs I, II and III showed an apparent dose-dependent inhibition of PLA2 and PLC activities, and all three proteins had a more potent inhibitory effect than lipocortins. The inhibition was overcome by high phospholipid substrate concentrations, for example, in the presence of 2.9 x 10(-9)M PLA2 and 2.6 x 10(-7)M CPB I, the inhibition decreased from 85 to 9% as phosphatidylethanolamine was increased from 10 to 100 microM. A similar result was observed in the case of PLC also. The evidence strongly suggests that the inhibitory effect of CPBI results from binding of the proteins to the phospholipid substrate rather than from a direct action on the phospholipase itself.
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PMID:[Inhibitory effects of calphobindins on phospholipase A2 and phospholipase C]. 138 68

The Ca2+ ion exerts a profound influence on cellular processes and an understanding of control mechanisms of intracellular Ca2 homeostasis while complex is mandatory in this discussion. The identification and recognition of prolonged sustained increase in [Ca2+]i as a manifestation of neurotoxin-induced destabilization of [Ca2+]i homeostasis will be related to a variety of neurotoxicant-induced cell injuries. The sites of toxicant interaction with ATP-regulated Ca2+ pumps located in the neuronal/glial membrane and/or calciosomes; availability of Ca2+ proteins; disruption in mitochondrial mechanisms for Ca2+ storage; triggers of voltage-dependent Ca2+ channels and modulation of the Na+/Ca2+ exchanger will be identified and related to presumptive toxin action. Failure of one or more of these systems will result in continuous elevation of ionized [Ca2+]i--a reflection of Ca2+ destabilization. The targets resulting from Ca2+ destabilization will be identified, to include phospholipase C activation, PLA2 activation, protein kinase C (PKC) translocation, and activation of Ca(2+)-dependent calpain 1. The use of specific inhibitors of neurotoxicity, e.g., natural sphingolipids, sphingosine, down regulation of PKC, inhibitors and activators of adenylate cyclase, and antiprotease agents will allow for investigation of the role of these final common pathways in the evolution of neurotoxicity.
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PMID:Ca(2+)-dependent processes as mediators of neurotoxicity. 150 13

The immediate reaction products of PLA2-mediated hydrolysis of phospholipids were tested for their ability to induce Ca2+ mobilization from internal stores in permeabilized ob/ob mouse pancreatic islets. Lysophospholipids and unsaturated fatty acids increased the free Ca2+ concentration in the incubation medium of permeabilized ob/ob mouse pancreatic islets. The potency of the lysophospholipids decreased in the following order: lysophosphatidylcholine = lysophosphatidylglycerol much greater than lysophosphatidylinositol greater than lysophosphatidylserine much greater than lysophosphatidylethanolamine. Arachidonic acid and palmitoleic acid had a potency comparable to lysophosphatidylinositol, while palmitic acid was ineffective. The Ca(2+)-mobilizing effect of inositol-1,4,5-trisphosphate (IP3) in permeabilized islet cells was additive to the lysophospholipid effect, indicating different sites of action. Both Ca(2+)-mobilizing effects were counteracted by the polyamine spermine, while the presence of Mg2+ shifted the Ca2+ concentrations to higher levels. Since not only an activation of a phospholipase C but also an activation of a phospholipase A2 with subsequent generation of lysophospholipids and free fatty acids is reported to occur in glucose-induced insulin secretion, the interaction of the phospholipase C reaction product IP3 with a lysophospholipid or an unsaturated fatty acid may affect the extent and duration of the rise in the free cytoplasmic Ca2+ concentration responsible for initiation of insulin secretion.
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PMID:Effect of lysophospholipids, arachidonic acid and other fatty acids on regulation of Ca2+ transport in permeabilized pancreatic islets. 158 37

Phospholipid metabolism is altered during ischemia and post-ischemic reperfusion. Past studies demonstrating elevated myocardial free fatty acid and lysophospholipid content infer accelerated phospholipid degradation involving phospholipase A activity. Recently, ischemic and post-ischemic reperfusion (reperfusion) have been shown to affect levels of phosphoinositide (PPI) degradation products. Considering the role of PPI turnover in regulation of cellular calcium homeostasis, our laboratory and others have suggested that alteration in the metabolism of the inositol phospholipids could play a role in the development of ischemia-induced calcium overload injury. Using an isolated rat heart model (Langendorff perfusion), this study examines the effect of global ischemia and reperfusion on ventricular phosphoinositide-specific phospholipase C (PLC) activity and PLA2 activity. The primary purpose was to determine if ischemia and reperfusion-induced changes in PLC activity could explain previously observed changes in PPI degradation products, and whether PLC and PLA2 activities were similarly or differentially altered by ischemia and reperfusion. PLC and PLA2 activities were measured in cytosolic and total membrane fractions from control (perfused), ischemic (5, 10, 30, and 60 min), and post-ischemic reperfused ventricular tissue. Phospholipase activity was determined under optimal in vitro conditions using exogenous radiolabeled substrates. Alterations in membrane-associated PPI-PLC activity correlated with reported ischemia and reperfusion-induced changes in ventricular content of PPI metabolites. Membrane PLC activity increased slightly at 5 min of ischemia, decreased significantly at 10 min of ischemia, and continued to decrease with longer duration of ischemia (73% of control after 60 min). Cytosolic PPI-PLC activity was decreased at 5 min, and then significantly increased by longer durations of ischemia, while cytosolic PLA2 activity was reduced at all time points. Pretreatment with muscarinic, alpha 1-adrenergic, beta-adrenergic, and adenosine receptor blockers did not alter ischemia-elicited changes in PLC activity. Reperfusion caused a 140% to 200% rise in the activities of all phospholipases in all fractions after 40 min of ischemia, but not after 10 min of ischemia. Results suggest 1) ischemia and reperfusion-elicited alterations in membrane-associated PPI-PLC activity can explain previously observed changes in phosphoinositide turnover metabolites, 2) cytosolic and membrane-associated PPI-PLC and PLA2 activities are not uniformly affected by ischemia, 3) reperfusion following ischemia of sufficient duration initiates uniform activation of PIP2-PLC and PLA2, and 4) because ischemia and reperfusion-induced changes in phospholipase activity can be detected under optimal in vitro assay conditions (removed from the in vivo ischemic microenvironment), it is likely that the enzymes themselves have been altered.
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PMID:Changes in phosphoinositide-specific phospholipase C and phospholipase A2 activity in ischemic and reperfused rat heart. 159 Jul 34

Isolated glomeruli from rats with bilateral ureteral obstruction (BUO) of 24-h duration produced significantly greater amounts of prostaglandin (PG) E2 and 6-keto-PGF1 alpha in vitro than glomeruli from sham-operated control (SOC) rats. This increase was abolished by the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat, given in vivo. To elucidate the mechanisms responsible for enhanced eicosanoid production by glomeruli from rats with BUO, we measured the activities of phospholipase (PL) A2 and C and cyclooxygenase in glomeruli isolated from SOC and BUO rats. L-alpha-Phosphatidylcholine (PC)-specific and L-alpha-phosphatidylethanolamine (PE)-specific PLA2 activities were significantly greater in glomerular membranes from rats with BUO than from SOC rats. Likewise, both the activity and amount of cyclooxygenase were significantly greater in glomerular membranes of rats with BUO. Cyclooxygenase and the PE-specific PLA2 in glomerular membranes of rats with BUO remained at the levels seen in SOC rats when animals were treated in vivo before BUO with the ACE inhibitor, enalaprilat, and the thromboxane synthase inhibitor, OKY-046. Thus inhibition of vasoconstrictor formation leads to subsequent inhibition of vasodilator formation. In contrast to PE-specific PLA2, PC-specific PLA2 activities were further increased in glomerular membranes from both SOC and BUO rats pretreated with the two drugs.s The activity of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PIP2 PLC) was significantly decreased in glomeruli from rats with BUO compared with SOC rats. We conclude that the increased synthesis of vasodilatory eicosanoids by glomeruli from rats with BUO may be mediated by enhanced activities of PE-specific PLA2 and cyclooxygenase, which are apparently stimulated by the vasoconstrictors angiotensin and thromboxane.
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PMID:Mechanism of enhanced eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction. 165 4

We have previously demonstrated phospholipase C (PLC) independent activation of phospholipase A2(PLA2) by epidermal growth factor (EGF) in glomerular mesangial cells in culture. In the current study using glass beads to permeabilize [3H]- or [14C]-arachidonate labelled mesangial cells we demonstrate that guanine nucleotides modulate the EGF-mediated stimulation of arachidonic acid release (75% inhibition with 100 microM GDP beta S and 108% augmentation with 100 microM GTP gamma S). GTP gamma S alone stimulated both the release of free arachidonic acid and production of diacylglycerol (DAG), while EGF itself neither stimulated DAG nor augmented the DAG response to GTP gamma S. These findings suggest the intermediacy of a G-protein in PLC-independent stimulation of PLA2 by a growth factor, and provide a model system for determining the relationship between G-protein intermediacy and the intrinsic tyrosine kinase activity of the growth factor receptor.
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PMID:A role for G-proteins in the epidermal growth factor stimulation of phospholipase A2 in rat kidney mesangial cells. 212 7

The bovine seminal plasma is formed mainly by secretions of epididymis and the glandular epithelia in ampulla, seminal vesicles, prostate and Cowper's glands. The contribution of each organ to the hydrolytic enzyme activities (glycosidases, exopeptidases, phospholipases) of the bull seminal plasma has been analyzed and is reviewed in this paper with special emphasis on the role of the accessory glands. Seminal vesicles seem to have a major role in the secretion of seminal plasma acid alpha-glucosidase, acid alpha-mannosidase and beta-N-acetylhexosaminidase, aminopeptidase A, dipeptidyl peptidase II and IV and gamma-glutamyl transpeptidase as well as Ca(2+)-dependent and Ca(2+)-independent phospholipases A2 with distinct substrate specificities, a choline-specific phospholipase C and a Co2+ (Mn2+)-activated sphingomyelinase. The enzyme pattern in the ampulla closely resembled that of the seminal vesicles and obviously contributes to the seminal plasma level of these hydrolases. The bull prostate and Cowper's glands contained a strong Ca(2+)-dependent phospholipase A2 activity. However, these glands may not contribute to the seminal plasma PLA2 activity. At ejaculation the epididymal spermatozoa are exposed to these enzymes. They may have a specific affinity to sugar, peptide or phospholipid residues at distinct sites of the sperm surface. These enzymes may also participate in the digestion of various other semen components to create a suitable milieu for the emitted spermatozoa.
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PMID:Hydrolases from bovine seminal vesicle, prostate and Cowper's gland. 213 63

The aim of this study is to clarify which signaling mechanism operates in Fc gamma receptor-mediated endocytosis in human neutrophils. Endocytosis of immune complexes was inhibited by antibodies directed to cell membrane phospholipase C (PLC) and A2 (PLA2) (maximal inhibition obtained was 57% and 28%, respectively), being almost abolished by these antibodies if used in combination (up to 91% inhibition). The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate, reversed this inhibitory effect. Four different PKC inhibitors (H-7, palmitoylcarnitine, sphingosine, and tamoxifen) produced a dose-dependent inhibition of endocytosis, up to over 80% in each case. H-8 (1-10 microM) which inhibits cyclic nucleotide protein kinases but not PKC had no effect upon endocytosis. It is concluded that Fc gamma receptor-induced activation of PLC and PLA2 triggers endocytosis by activation of PKC.
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PMID:Protein kinase C controls Fc gamma receptor-mediated endocytosis in human neutrophils. 214 63

Phospholipases, a group of enzymes that catalyze the hydrolysis of membrane phospholipids, are classified according to the bond cleaved in a phospholipid into PLA1 (EC 3.1.1.3), PLA2 (EC 3.1.1.4), PLB (EC 3.1.1.5), PLC (EC 3.1.4.3), and PLD (EC 3.1.4.4). This paper reviews source and structure of PLA2 and the involvement of PLA2 and PLC in several biological phenomena, such as, signal transduction, photoreception, biosynthesis of lung surfactant, sperm motility, and fertilization. New assays for PLA2 activity and concentration in biological fluids are discussed. Phospholipases are involved in many inflammatory reactions by making arachidonate available for eicosanoid biosynthesis. The determination of PLA2 activity and mass concentration in plasma is useful in the diagnosis and prognosis of pancreatitis and of septic shock. Naturally occurring phospholipase inhibitors, such as lipocortins act as second messengers in the anti-inflammatory response to steroids. Lipocortins may be valuable therapeutic agents, because they are more specific in their anti-inflammatory action than glucocorticoids; therefore, they are less likely to produce harmful side effects.
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PMID:Phospholipases in biology and medicine. 225 31

The CPAE bovine endothelial cell line may be stimulated to produce eicosanoids. Leukotriene D4 increased the release of arachidonic acid primarily by activating phospholipase A2 while bradykinin activated the phospholipase C pathway. Cells pretreated with dexamethasone, a phospholipase A2 inhibitor, no longer responded to stimulation by LTD4 but did release arachidonic acid when treated with bradykinin. Aspirin blocked bradykinin-stimulated production of arachidonic acid but left the response to LTD4 unaffected. We conclude that these cells produce eicosanoids by activation of both PLA2 and PLC, and that the two different methods of arachidonic acid release can be distinguished by using the common anti-inflammatory drugs aspirin and dexamethasone.
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PMID:Differential effects of aspirin and dexamethasone on phospholipase A2 and C activities and arachidonic acid release from endothelial cells in response to bradykinin and leukotriene D4. 310 70


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