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)

Phosphoinositide phospholipase C activity was investigated in human melanoma grown as solid tumor xenografts in nude mice. The enzyme was dependent on calcium for activity and was stimulated by the detergent deoxycholate. The pH optimum was 5.5 in the absence of detergent, and in the presence of deoxycholate two pH maxima were present, 5.5 and 7.2. Phospholipase C activity was inhibited by the sulfhydryl reagent dithionitrobenzoate with an IC50 in the micromolar range. Phospholipase C activity was distributed widely in mouse tissues. The enzyme showed a progressive increase in activity from heart, liver, lung, colon, spleen, to brain tissue. Mouse and human melanomas grown as solid tumors had higher phospholipase C activity than mouse brain. The relatively high activity of this enzyme in melanoma may suggest a biological role for phospholipase C in solid tumor growth.
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PMID:Characterization of phosphatidylinositol phospholipase C activity in human melanoma. 230 36

The present study was designed to study the functional properties of Angiotensin II (Ang II) binding sites in vascular smooth muscle cells in the Milan hypertensive rat (MHS), a model of low renin hypertension. Smooth muscle cells from MHS rats exhibited increased growth in culture in comparison with the Milan normotensive strain (MNS) as determined by population doubling times (24.5 +/- 2 and 34.8 +/- 2 hours, n = 4, respectively). Hormone receptor number, evaluated by binding assays using [125I]Ang II, showed no difference in either receptor number or affinity for both cell types. The functional responsiveness of Ang II receptors was evaluated by measuring the activation of phospholipase C, Na(+)-H+ exchange, and cytosolic Ca2+ levels. Phospholipase C activity was determined as tritium-labeled inositol trisphosphate and bisphosphate release before and after 15-second exposure to 10(-7) M Ang II. Ang II-stimulated phospholipase C activity in MNS (p less than 0.02) but not in MHS cells. Na(+)-H+ exchange was measured as the dimethylamiloride-sensitive 22Na+ influx into acid-loaded vascular smooth muscle cells with and without 10(-7) M Ang II. In MNS cells, Ang II significantly stimulated (p less than 0.001) antiporter activity but not in MHS cells, which showed a uniformly blunted response. MHS cells exhibited higher basal cytosolic Ca2+ levels than MNS cells, but Ca2+ rapidly increased in the presence of Ang II in MNS but not in MHS cells. Direct activation of phospholipase C by GTP-gamma-S in permeabilized cells indicated that both strains exhibited similar coupling levels by guanine-nucleotide binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular smooth muscle cells from the Milan hypertensive rat exhibit decreased functional angiotensin II receptors. 234 21

Previous studies have shown that external calcium (Ca2+) is required for the effects of angiotensin II (AII) on aldosterone secretion in adrenal glomerulosa zone. Using bovine adrenal glomerulosa cells prepared by collagenase dispersion, we examined whether external Ca2+ is required for the activation of phospholipase C by AII. Adrenal glomerulosa cells were exposed to Ca-EGTA buffered media to provide accurate estimates of external free Ca2+ concentrations. Phospholipase C activation was evaluated by measurement of inositol phosphates production. At 0.1 microM Ca2+ and less, sustained AII effects on inositol monophosphate (IP), inositol bisphosphate (IP2) and inositol trisphosphate (IP3) were markedly inhibited. Increasing the Ca2+ concentration to 50 microM or greater fully restored AII-induced inositol phosphates production. AII-induced increases in cytosolic Ca2+ measured by Quin-2 fluorescence, were diminished at lower external Ca2+ concentrations. Treating adrenal glomerulosa cells with Chelex-100, a strong Ca2+ binding resin, blocked early activation of phospholipase C by AII. Inhibition of IP3 production was also observed when inhibitors of Ca2+ movement across the plasma membrane were used, viz., La2+, TMB-8 and nifedipine. The requirement for Ca2+ during AII-induced activation of phospholipase C may be explained, at least partly by a requirement for Ca2+ at a site between the AII receptor and Phospholipase C.
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PMID:External calcium is required for activation of phospholipase C by angiotensin II in adrenal glomerulosa cells. 236 56

Fluoride interacts with G proteins and, consequently, stimulates phospholipase C as measured by the formation of inositol phosphates and phosphatidic acid. In human platelets this paralleled platelet aggregation and the activation of phosphorylation of substrates of protein kinase C (47kDa protein) and myosin light chain kinase (20kDa protein). Phospholipase C activation by fluoride was inhibited by dibutyryl cyclic AMP and by agents that increase cyclic AMP levels such as iloprost and forskolin. This information suggest that cyclic AMP affects the G protein associated with the stimulation of phospholipase C.
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PMID:Activation of platelet phospholipase C by fluoride is inhibited by elevation of cyclic AMP. 246 3

The biochemical events encompassing the dephosphorylation of protein kinase C substrates by protein kinase A activators have been investigated in a neurotumor cell line, NCB-20. Treatment of [32P]orthophosphate-labeled cells with protein kinase A activators (e.g. forskolin, dibutyryl cAMP, prostaglandin E1) resulted in an inhibition of protein kinase C activity due to a failure of the protein kinase C complex to translocate into the membrane. Phospholipase C activity, as measured by the synchronous release of diacylglycerol and inositol phosphates (inositol 1,4,5-trisphosphate, inositol 1,4-bisphosphate, and inositol 1-phosphate) in response to bradykinin, was inhibited up to 50% following exposure to protein kinase A activators. At the same time, phospholipase C-specific inositol phospholipid substrates (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) were found to accumulate in NCB-20 cells following treatment with protein kinase A activators. This suggests that phospholipase C may be altered through protein kinase A-mediated protein phosphorylation. Second messenger generation (inositol phosphates, diacylglycerol, and Ca2+) is therefore inhibited through cyclic AMP-mediated shutdown of the inositol lipid cycle at the level of phospholipase C.
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PMID:Rapid dephosphorylation of protein kinase C substrates by protein kinase A activators results from inhibition of diacylglycerol release. 247 91

In order to define the molecular mechanisms involved in the hypertrophy of the arterial walls observed in essential hypertension, vascular smooth muscle cells were isolated from aortas of spontaneously hypertensive (SHR) and control (WKY) rats, and cultured (until the 4th sub-culture) in the presence of growth factors (foetal calf serum: FCS) and various vasoactive drugs. Growth rate was determined by cell counting and measurement of nuclear thymidine incorporation, and activation of phospholipase C by measurement of the inositol phosphates formed from preincorporated tritiated myo-inositol; the expression of the cellular oncogenes, c-fos and c-myc was visualized by hybridization of Northern blots performed from total RNA. In the presence of low concentrations of FCS (2 p. 100, 5 p. 100) angiotensin II (10(-7)M) and bradykinin (3 X 10(-6)M) increase the growth of both kind of cells. The inositol phosphate formation and the expression of c-fos and c-myc are also dose-dependently stimulated by these vasoactive drugs, and the cultures from SHR are more responsive than those from WKY rats. Phospholipase C hyperreactivity therefore appears to be involved in the increased proliferative ability of vascular smooth muscle cells from SHR. However other molecular processes may be involved, as suggested by the growth inhibition exerted by heparin without any action on PLC activity.
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PMID:[Molecular mechanisms controlling the proliferation of aortic smooth muscle cells in spontaneously hypertensive rats]. 251 Jun 66

The phospholipase C gene from Clostridium perfringens was isolated, and its sequence was determined. It was found that the structural gene codes for a protein of 399 amino acid residues. The NH2-terminal residues have the typical features of a signal peptide and are probably cleaved after secretion. Escherichia coli cells harboring the phospholipase C gene-containing plasmid expressed high levels of this protein in the periplasmic space. Phospholipase C purified from E. coli transformants was enzymatically active, hemolytic to erythrocytes, and toxic to animals when injected intravenously. The phospholipase C gene from a related organism, Clostridium bifermentans, was also isolated. The two phospholipase C genes were found to be 64% homologous in coding sequence. The C. bifermentans protein, however, was 50-fold less active enzymatically than the C. perfringens enzyme.
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PMID:Cloning and expression of the phospholipase C gene from Clostridium perfringens and Clostridium bifermentans. 253 56

Phospholipase C (PLC)-mediated degradation of polyphosphoinositides (phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP] was found to be present in rat heart ventricular soluble and total membrane fractions (100,000g supernatant and pellet). Distribution of polyphosphoinositide-specific phospholipase C activity between the membrane and soluble fraction was approximately 63 and 33% of total activity, respectively, whereas, phosphatidylinositol (PI) degradation could be detected only in the soluble fraction. Optimal PIP2-PLC activity occurred at a pCa2+ of 4.5. A similar peak in PIP-PLC activity could be demonstrated in soluble and membrane preparations; however, the rate of PIP degradation in the soluble fraction continued to increase at the highest calcium level tested (pCa2+ 3). With the exception of Sr2+, other noncalcium polycations did not support homogenate PIP2-PLC activity. In the presence of Ca2+, addition of Mg2+, La3+, or Sr2+ (10(-3) M) inhibited PIP2-PLC while Mn2+ and Gd3+ stimulated activity. In both the total membrane and soluble fractions, maximal polyphosphoinositide degradation occurs at pH 5.5 and 6.8. The detergents deoxycholate, cholate, and saponin exert a biphasic effect on PIP2-PLC activity (stimulating at lower concentrations and inhibiting at higher concentrations). The deoxycholate effect is observed in both the cytosolic and membrane fractions. Neutral and cationic detergents inhibit PIP2-PLC activity in a concentration-dependent manner. Similar to cytosolic PI-PLC activity, PIP2-PLC appears to depend on intact sulfhydryl groups. In the presence of a mixture of all three inositol phospholipids or the three phosphoinositides plus noninositol phospholipids, polyphosphoinositides are preferentially degraded.
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PMID:Characterization of phospholipase C-mediated polyphosphoinositide hydrolysis in rat heart ventricles. 253 55

The purpose of this investigation was to study the effects of a distinct type of phospholipase C on sarcolemmal Na+-Ca2+ exchange. With this phospholipase C (Staphylococcus aureus), treatment of cardiac sarcolemmal vesicles resulted in a specific hydrolysis of membrane phosphatidylinositol. This hydrolysis of phosphatidylinositol also released two proteins (110 and 36 kDa) from the sarcolemmal membrane. Phospholipase C pretreatment of the sarcolemma resulted in an unexpected stimulation of Na+-Ca2+ exchange. The Vmax of Na+-Ca2+ exchange was increased but the Km for Ca2+ was not altered. This stimulation was specific to the Na+-Ca2+ exchange pathway. ATP-dependent Ca2+ uptake was depressed after phospholipase C treatment, but passive membrane permeability to Ca2+ was unaffected. Sarcolemmal Na+,K+-ATPase activity was not altered, whereas passive Ca2+ binding was modestly decreased after phospholipase C pretreatment. The stimulation of Na+-Ca2+ exchange after phosphatidylinositol hydrolysis was greater in inside-out vesicles than in a total population of vesicles of mixed orientation. This finding suggests that the cardiac sarcolemmal Na+-Ca2+ exchanger is functionally asymmetrical. The results also suggest that membrane phosphatidylinositol is inhibitory to the Na+-Ca2+ exchanger or, alternatively, this phospholipid may anchor an endogenous inhibitory protein in the sarcolemmal membrane. The observation that a transsarcolemmal Ca2+ flux pathway may be stimulated solely by phosphatidylinositol hydrolysis independently of phosphoinositide metabolic products like inositol triphosphate is novel.
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PMID:Role of phosphatidylinositol in cardiac sarcolemmal membrane sodium-calcium exchange. 254 59

Phospholipase C from Clostridium perfringens, when injected into a closed loop of the rat small intestine in vivo, caused an increase in the activity of intraluminal N-acetyl-beta-glucosaminidase and mucosal permeability to sodium fluorescein, indicating damage to the mucosa. Phospholipase C also caused an influx of granulocytes (neutrophils) into the mucosa, as shown by the myeloperoxidase activity--a granulocyte neutrophil marker, and increased localized lipid peroxidation. Pretreatment of animals with quinacrine, a known inhibitor of phospholipase A2, prevented the increases in the luminal N-acetyl-beta-glucosaminidase activity, mucosal permeability, malondialdehyde and myeloperoxidase activity after deposition of phospholipase C in the gut lumen. It is concluded that phospholipase C might impair the function of the mucosal barrier and increase the permeability of the gut to undesirable molecules and pathogens. Part of its action may be mediated via phospholipase A2 activation since pretreatment with quinacrine afforded protection.
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PMID:Phospholipase C-mediated intestinal mucosal damage is ameliorated by quinacrine. 255 3


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