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)

The effect of phospholipase C on two isozymes (alpha (+) and alpha forms) of rat brain (Na+ + K+)-ATPase and the temperature-dependence of their activities were investigated. Phospholipase C from Clostridium welchii inhibited the activities of the enzymes treated with and without pyrithiamin or N-ethylmaleimide, a preferential inhibitor of the alpha (+) form, but the extent of the inhibition was higher in the control enzyme than in the treated enzymes. The treatment of the (Na+ + K+)-ATPase with phospholipase C altered a ratio between high- and low-affinity components for ouabain inhibition. It also caused the similar change in a ratio between the alpha (+) and alpha forms of Na+-stimulated phosphorylation from [gamma-32P]ATP. These findings indicate that the alpha (+) form of rat brain (Na+ + K+)-ATPase is more sensitive to phospholipase C than the alpha form. Analysis of Arrhenius plots of the activities of the control and pyrithiamin-treated enzymes showed that there was a difference between the two enzymes in a break point. We suggest that two isozymes of rat brain (Na+ + K+)-ATPase differ in the interaction with phospholipids or in the lipid-environment.
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PMID:Difference in phospholipid dependence between two isozymes of brain (Na+ + K+)-ATPase. 301 25

Ouabain-sensitive 86Rb+ uptake by isolated rat hepatocytes was studied to elucidate how Ca2+-mobilizing hormones stimulate the Na+-pump. Stimulation of this uptake was observed with concentrations of vasopressin ([8-arginine]vasopressin, AVP), angiotensin II, and norepinephrine which elicited Ca2+ mobilization and phosphorylase activation. These results suggested that changes in cytosolic Ca2+, mediated by inositol trisphosphate, might trigger sodium pump stimulation by AVP. However, in hepatocytes incubated in Ca2+-free Krebs-Henseleit buffer, Na+-pump activity was not altered over 15 min by either 1.5 mM EGTA or 1.5 mM Ca2+. Furthermore, incubation of cells in 5 mM EGTA for 15-30 min drastically impaired the ability of AVP to increase cytosolic Ca2+, but only modestly attenuated AVP-stimulated Na+-pump activity. Two tumor promoters, phorbol myristate acetate (PMA) and mezerein, stimulated Na+/K+-ATPase-mediated transport activity. Similarly, addition of synthetic diacylglycerols or of exogenous phospholipase C from Clostridium perfringens to increase endogenous diacylglycerol levels also resulted in a stimulation of the Na+-pump in the absence of changes in cytosolic or total cellular Ca2+ levels. Stimulation of the Na+-pump by the combination of maximal concentrations of PMA and AVP did not produce an additive response, and both agents displayed a transient time course, suggesting that the two agents share a common mechanism. Stimulation of the Na+-pump by AVP and PMA was not blocked by amiloride analogs which inhibit Na+/H+ exchange, but these compounds blocked the action of insulin. These data suggest that the elevated Na+/K+-ATPase-mediated transport activity observed in hepatocytes following exposure to Ca2+-mobilizing hormones is a consequence of stimulated diacylglycerol formation and may involve protein kinase C.
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PMID:The hormone-sensitive hepatic Na+-pump. Evidence for regulation by diacylglycerol and tumor promoters. 302 43

Ouabain and related cardiac glycosides stimulate phospholipase C activity 5-fold in rat pinealocytes. The combined treatment of ouabain and norepinephrine, which also stimulates phospholipase C, produces an additive effect. The effects of either ouabain or norepinephrine are blocked by EGTA. However, there are notable differences. The stimulatory effect of ouabain is lost when extracellular Na+ is reduced to 20 mM and is not blocked by prazosin. In contrast, the stimulatory effect of norepinephrine is not blocked when extracellular Na+ is reduced to 20 mM but is blocked by prazosin. Ouabain appears to increase phospholipase C activity through a mechanism involving inhibition of Na+,K+-ATPase, and an accumulation of intracellular Na+ and Ca2+, not involving alpha 1-adrenoceptors. These findings raise the possibility that activation of phospholipase C might be a more general effect of cardiac glycosides.
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PMID:Cardiac glycosides stimulate phospholipase C activity in rat pinealocytes. 303 Mar 2

Mammalian cells treated with low concentrations of phospholipase C become permeable to the protein toxin alpha-sarcin. A similar permeabilization is not induced upon treatment with other lipases such as phospholipase A2, sphingomyelinase, or cholesterol esterase. Concentrations of 10 micrograms/ml alpha-sarcin almost completely blocked translation in HeLa cells treated with 0.3 U/ml phospholipase C (PL-C) for 1 h. In contrast, 200 micrograms/ml of alpha-sarcin had no effect at all on protein synthesis in untreated cells. Other macromolecules such as horseradish peroxidase and luciferase also enter into cells if they are treated with phospholipase C. This permeabilization method is fully reversible. As soon as 5 min after PL-C removal, the cells become impermeable to alpha-sarcin. Other metabolites such as uridine nucleotides are partially released after PL-C incubation, whereas the content of 86Rb+ remains at control levels, probably because the Na+/K+ ATPase activity increases.
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PMID:Exogenous phospholipase C permeabilizes mammalian cells to proteins. 313 47

The behaviour of Ca2+ ATPase activity in relation to Ca2+ transport process was studied under different experimental conditions in canine cardiac microsomal fraction predominantly containing sarcoplasmic reticulum. The total Ca2+ concentration required for half maximal activation (Ka) of microsomal Ca2+ ATPase and Ca2+ uptake did not differ significantly, unless 0.1 mmol/l EGTA was present in the incubation media. Pretreatment of cardiac microsomes with membrane disruptive agents like phospholipase A, trypsin as well as deoxycholate strongly increased (2-3 fold) Ca2+ ATPase activity but uptake rate of Ca2+ declined. Only in phospholipase C and beta-glucuronidase pretreatment, a parallel decrease of Ca2+ ATPase and uptake was observed. In presence of excess (free)Ca2+ (greater than 10 mumol/l) both Ca2+ ATPase as well as Ca2+ uptake were inhibited, however, Ca2+ binding process remained unaltered. Likewise, low pH completely altered the relation between Ca2+ binding and ATPase activity; whereas Ca2+ ATPase was inhibited, Ca2+ binding did not change. Our present data provide evidence for some cellular factors that may be involved in producing uncoupling of microsomal Ca2+ ATPase from Ca2+ accumulation process that was previously observed in various pathological situations.
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PMID:Behaviour of cardiac microsomal Ca2+ pump under conditions that may simulate pathological situations. 316 76

Daily subcutaneous injection of gentamicin (100 mg/kg) for 2 days produced a significant decrease in the activities of alkaline phosphatase, a brush-border membrane marker, and Na+-K+ ATPase, a basolateral membrane marker, in adult rat kidney cortex. Analysis of homogenate and lysosomal fractions revealed a significant rise in the concentration of total renal cortical phospholipid, phosphatidylserine, phosphatidylcholine, and phosphatidylinositol. In the lysosomal fraction, an increase in the levels of phosphatidylglycerol and phosphatidylethanolamine was also noted. Daily, oral chlorphentermine (60 mg/kg) administration for 5 days significantly reduced renal Na+-K+ ATPase without a marked change in alkaline phosphatase. As in the case of gentamicin, chlorphentermine produced a significant elevation in phosphatidylserine, phosphatidylcholine, and phosphatidylinositol as well as total phospholipid in both the homogenate and lysosomal fractions of kidney cortex. The observed chlorphentermine- or gentamicin-induced renal phospholipidosis was associated with a significant reduction in the activity of phosphatidylinositol-specific phospholipase C. The drug-induced inhibition of phospholipase C was quantitatively equal in the renal cortical homogenate and lysosomal fractions. In addition, gentamicin significantly inhibited the activity of phosphatidylserine-phospholipase C and phosphatidylcholine-phospholipase C in renal cortical homogenate. In contrast, only the activity of phosphatidylinositol-specific phospholipase C was decreased in chlorphentermine-treated kidneys. Evidence thus indicates that the gentamicin-induced accumulation of phospholipid in renal cortical lysosomes is associated with inhibition of various forms of phospholipase C, while in the case of chlorphentermine the inhibition of different phospholipases may be involved in phospholipid accumulation.
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PMID:Cationic amphiphilic drug-induced renal cortical lysosomal phospholipidosis: an in vivo comparative study with gentamicin and chlorphentermine. 342 75

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

The role of lipids of the sarcotubular membranes in their Ca(++) uptake and Mg-ATPase activities was investigated. Treatment of the membranes with phospholipase C inhibits both processes. Treatment with phospholipase A and phospholipase D, which results in massive hydrolysis of the sarcotubular phospholipids, does not inhibit either the Ca(++) uptake or the Mg-ATPase activities, nor does treatment with the polyene antibiotics affect these processes. Essential fatty acid deficiency alters sarcotubular membrane lipids; they contain much less stearic, linoleic, and arachidonic acids and much more oleic and eicosatrienoic acids than normally, but do not lose the ability to actively sequester Ca(++). It is concluded that neither nonpolar lipids nor the nonpolar regions of polar lipids are involved in Ca(++) sequestering and Mg-ATPase activities of the sarcotubular membranes. Of the polar components, the phosphoryl moiety of the phospholipids is required for both activities. However, the phosphoryl group appears to be required for the maintenance of the membranous structure necessary for Ca(++) sequestration rather than serving specifically in the active transport process. That treatment with phospholipase D, which results in the conversion of much of the sarcotubular phospholipid from a dipolar to an anionic structure, does not affect Ca(++) uptake activity is a most remarkable finding.
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PMID:Relation of lipid structure of sarcotubular vesicles to Ca++ transport activity. 423 45

Colloidal iron staining, calcium binding and enzyme activities were studied in the isolated rat heart sarcolemma. Colloidal iron staining of the sarcolemma revealed a high density of negatively charged sites associated with the cell surface. This membrane fraction was found to have calcium binding activity at both low (0.1 mM) and high (1.25 mM) concentrations of calcium. Pretreatment of the sarcolemma with either trypsin, phospholipase C or neuraminidase, was associated with a reduction in colloidal iron staining as well as decreased calcium-binding activity at high concentrations of calcium. Calcium binding at low concentrations was decreased by both trypsin and neuraminidase. Mg2+ ATPase, Ca2+ ATPase, and Na+-K+ ATPase activities were altered by neuraminidase and trypsin treatments, whereas phospholipase C treatment altered Na+-K+ ATPase only. It is concluded that both surface negative charge and calcium-binding sites associated with the isolated rat heart sarcolemma are contributed by a mosaic of biomolecules including proteins, phospholipids and glycoproteins, and alterations in the surface charge may influence the activities of membrane-bound enzymes.
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PMID:Negatively charged sites and calcium binding in the isolated rat heart sarcolemma. 616 50

ATPase activity and Ca2+ uptake were examined in microsomal membrane fractions isolated from guinea pig stomach smooth muscle which had been exposed to phospholipase C (PLC). Basal Mg2+-ATPase, Na+, K+-ATPase and Ca2+, Mg2+-ATP activities were inhibited in a time dependent manner by PLC treatment. There was positive correlations between each of these ATPase activities and total phospholipid content of the microsomal fraction. Phosphotidylcholine restored Ca2+, Mg2+-ATPase activity of the microsomal fraction isolated from the tissue which had been treated with PLC for 30 min but not after 60 min. Ca2+ uptake in the presence of ATP by microsomal fraction from tissue treated with PLC for 60 min was significantly decreased. The results provide a cellular basis for the inhibitory effect of PLC on contractility of stomach smooth muscle.
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PMID:ATPase activity and calcium uptake of microsomes isolated from stomach smooth muscle after exposure to phospholipase C. 622 98


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