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)

1. The composition and metabolism of phospholipids were studied in various tissues from both normal and dystrophic mice of the 129 ReJ strain. Phospholipids extracted from forebrain, spinal cord, sciatic nerve and plasma were fractionated by t.l.c. and measured. 2. Very significant alterations were found in the choline phospholipids from these tissues, except forebrain. Plasma phosphatidylcholine in the dystrophic mouse was increased by 38%. There was a 2-fold increase in lysophosphatidylcholine in the spinal cord of dystrophic mice. The sciatic nerve showed a marked decrease in sphingomyelin content, which is approximately half of that in the controls. 3. Five enzymes involved in phosphatidylcholine metabolism [namely cholinephosphotransferase (EC 2.7.8.2); phospholipases A (EC 3.1.1.4, EC 3.1.1.32); lysophospholipase (EC 3.1.1.5); lysophosphatidylcholine acyltransferase (EC 2.3.1.23); phospholipase C (EC 3.1.4.3)] were studied in tissue preparations from forebrain, spinal cord, sciatic nerves, gastrocnemius muscles and liver. 4. Activities of phospholipases A and C were significantly increased, about 5-fold and 60% respectively, in gastrocnemius muscle of dystrophic mice compared with controls. Phospholipases A also showed 50% higher activity in the sciatic nerves of dystrophic than of normal mice. Lysophosphatidylcholine acyltransferase activities were significantly increased in the sciatic nerves and spinal cord, by 50-100% over that of the controls. The forebrain and spinal cord from dystrophic mice, however, had only 60% of lysophospholipase activities of that of the normal control. Cholinephosphotransferase activity was unchanged in these tissues from both normal and dystrophic mice. 5. It is suggested that are number of features of mouse muscular dystrophy related to altered membrane structure and function can be rationalized in terms of changes in lipid composition and metabolism.
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PMID:Phospholipid composition and metabolism in mouse muscular dystrophy. 72 3

The effects of lipoprotein lipase, phospholipase A2 and phospholipase C on chylomicron phosphatidylcholine and triacylglycerol were studied with rat lymph chylomicrons containing phosphatidylcholine labeled with [14C]oleic acid. Lipoprotein lipase purified from bovine milk readily hydrolyzed chylomicron phosphatidylcholine to lysophosphatidylcholine and fatty acid, and triacylglycerol to monoacylglycerol, fatty acid and glycerol. The rates of hydrolysis of phosphatidylcholine and triacylglycerol increased with enzyme concentration, and both decreased when fatty-acid binding sites on albumin in the incubation medium were limited. The proportion and amount of phosphatidylcholine hydrolyzed was always less than that of triacylglycerol. Analyses of hydrolytic products showed that lipoprotein lipase cleaved the 1-acyl ester bond of phosphatidylcholine. The findings indicate that lipoprotein lipase can account for some of the phospholipase A1 activity found in postheparin plasma. Phospholipase A2 and phospholipase C hydrolyzed chylomicron phosphatidylcholine, greater than 92% in 10 min, but not triacylglycerol. The resultant phosphatidylcholine-deficient chylomicrons, which could be concentrated by ultra-centrifugation and resuspended in incubation medium, were readily depleted of triacylglycerol when incubated with lipoprotein lipase. The findings indicate that phosphatidylcholine can be removed from the surface film of chylomicrons without disrupting the particles or blocking the action of lipoprotein lipase on the core triacylglycerol.
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PMID:Hydrolysis of chylomicron phosphatidylcholine in vitro by lipoprotein lipase, phospholipase A2 and phospholipase C. 94 90

Phospholipids accumulate within the lysosomes of various cells from individuals taking amiodarone. Studies on cultured cells suggest that inhibition of lysosomal phospholipase A1 and phospholipase A2 by amiodarone may be responsible for this derangement in phospholipid metabolism. Inhibition of lysosomal phospholipases by amiodarone has been suggested as a mechanism of its toxicity, but this relationship has not been clearly established. To examine this question, membrane phospholipids of cultured bovine pulmonary artery endothelial cells (BPAEC) were labeled with 14C-stearic acid, 3H-arachidonic acid, 14C-choline, or 14C-ethanolamine. Radiolabeled BPAEC were then exposed to various concentrations of amiodarone, and endothelial phospholipase activity was measured by isolating and quantifying various phospholipase products. These findings were compared to a standard indicator of endothelial cytotoxicity using 51Cr release. Six-hour exposures to 5 to 20 micrograms/ml amiodarone produced no BPAEC toxicity and were accompanied by some evidence of decreased phospholipid hydrolysis. At concentrations above 20 micrograms/ml, amiodarone caused significant BPAEC toxicity as indicated by 51Cr release, and this was closely associated with the liberation of substantial amounts of 3H-arachidonic acid and 14C-stearic acid from phosphatidylcholine and phosphatidylethanolamine. In BPAEC labeled with 14C-choline and 14C-ethanolamine, cytotoxic doses of amiodarone caused accumulations of 14C-phosphocholine and phosphorylethanolamine, expected products of phospholipase C, but without increases in phospholipase A products. We conclude that exposure of BPAEC to toxic concentrations of amiodarone is associated with extensive hydrolysis of phosphatidylcholine and lysophosphatidylethanolamine via a phospholipase C-specific mechanism, and suggest that this may be a mechanism in the pathogenesis of amiodarone toxicity.
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PMID:Amiodarone-induced endothelial injury is associated with phospholipase C-mediated hydrolysis of membrane phospholipids. 145 16

The effect of exposure of porcine pulmonary artery endothelial cells to hypoxic (0% O2) and normoxic (20% O2) conditions for 24 and 48 h on phospholipid metabolism was studied. Sonicates prepared from endothelial cells that were exposed to 24 h of hypoxia showed significant increases in phospholipase A1 (91%), phospholipase C (75%), and diacylglycerol lipase (57%) activities. Hypoxic exposure of cells for 48 h caused an increase in diacylglycerol lipase activity (54%) only. Hypoxia also caused significant decreases in ATP levels and ATP-dependent arachidonyl coenzyme A (CoA) synthetase activity. Phospholipase A2, lysophosphatidylcholine acyltransferase, and diacylglycerol acyltransferase activities were not influenced by 24 or 48 h of hypoxia. When endothelial cells were prelabeled with [3H]arachidonic acid and then exposed to hypoxia, increased counts were recovered from the free fatty acid fraction of medium and from the cell fatty acid esters, lysophospholipids, diacylglycerols, and triacylglycerols. There was a concomitant decreased recovery of counts from cell phospholipids. These results indicate that hypoxic exposure of endothelial cells altered phospholipid metabolism by activating deacylation pathways and inhibiting reacylation via ATP-dependent arachidonyl CoA synthetase.
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PMID:Effect of hypoxia on phospholipid metabolism in porcine pulmonary artery endothelial cells. 159 Apr 10

We have determined the concentration of free fatty acids in membranes of slices prepared from the dentate gyrus following the induction of long-term potentiation in the anaesthetized rat. Compared to unpotentiated tissue, there was a significant increase in the concentration of free arachidonic acid 2.5 min, 45 min and 3 h after induction of long-term potentiation. There was no corresponding increase in oleic, stearic or palmitic acids. To account for the increase in free arachidonate, the activities of phospholipase A2, phospholipase A1 and phospholipase C were determined at the same three time intervals in control and potentiated tissue. Two-and-a-half minutes after the induction of long-term potentiation, activity of phospholipase A2 was enhanced, while at 45 min, and at 3 h phospholipase C activity was increased. These results suggest that the liberation of free arachidonate is due initially to phospholipase A2 activity, but that at later stages of long-term potentiation, control switches to phospholipase C. Subcellular fractionation experiments revealed an increase in free arachidonate in the postsynaptic density fraction 45 min after induction of long-term potentiation, without significant changes in synaptosomal- or glial-enriched fractions. These results are consistent with the hypothesis that arachidonic acid, released from a postsynaptic site, acts as a trophic retrograde synaptic signal in long-term potentiation in the dentate gyrus.
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PMID:Increase in arachidonic acid concentration in a postsynaptic membrane fraction following the induction of long-term potentiation in the dentate gyrus. 166 36

Muscarinic receptors are involved in CNS neurotransmissions and have been shown to transduce their message by modulating cAMP, calcium, inositol phosphates, and more recently, by liberating arachidonic acid via phospholipase A1. We have previously shown that the alpha 1-adrenergic and 5-HT2 serotonergic neurotransmitter receptors cause the release of arachidonic acid from spinal cord and hippocampal neurons, respectively, in primary culture. In this study, we demonstrated a muscarinic receptor-mediated release of arachidonic acid in these two neural segments which occurred independent of phosphatidylinositol-specific phospholipase C. This release of arachidonic acid was neuronal (not glial) in origin and exhibited M1 muscarinic receptor pharmacology.
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PMID:Muscarinic receptors mediate the release of arachidonic acid from spinal cord and hippocampal neurons in primary culture. 212 13

We have examined effects of quaternary ammonium compounds on the in vitro degradation of endogenous lipids in isolated lysosomes. The degree of lipid degradation was assessed by determining hydrolysis products of labeled lipid. Lipolysis was inhibited by quaternary ammonium compounds. The degrees of inhibition were as follows: ethidium bromide greater than N-methylatropinium bromide (NMA) greater than tubocurarine. The inhibition of lipolysis by these quaternary ammonium compounds is not necessarily correlated with the differences in their polarities, molecular weight or structures. The degradation of three phospholipid classes was inhibited by NMA with phosphatidylcholine the most vulnerable. The effect of NMA on the hydrolysis of [14C]dipalmitoylphosphatidylcholine (phospholipid) by lysosomal soluble proteins was also examined. The effect of NMA on phospholipase A1 was assessed by the formation of lysophosphatidylcholine, and that on phospholipase C was assessed as the sum of mono- and diglyceride formations. The action of NMA on the phospholipid degradation was similar to that of cationic amphiphilic drugs, but it differed somewhat from that of chloroquine for each enzyme. From these results, it was concluded that one of the inhibitory mechanisms of phospholipid degradation by NMA was the direct interaction between NMA and phospholipase A1 or C.
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PMID:Effects of quaternary ammonium compounds on the degradation of lipids in lysosomes. 274 50

The effects of gentamicin on phospholipid levels and metabolism and the uptake of phosphatidylcholine (PC) adsorbed to low-density lipoprotein (LDL) were investigated in cultured human proximal tubular (PT) cells. Cells incubated with gentamicin (0.3 mM) for one to 21 days had a similar increase in the cell number and protein as compared to control cells. However, the cellular levels of phosphatidylcholine (PC) and sphingomyelin (SM), but not other phospholipids, increased in a time-dependent manner. Incubation of gentamicin (0.3 to 3.0 mM) resulted in a concentration-dependent increase in the cellular levels of PC (50% to 320%) and SM (20% to 40%). Gentamicin stimulated the incorporation of [14C]-acetate into diacylglycerol, PC, and SM in the order of 300%, 66%, and 20%, respectively, but not into lysophosphatidylcholine (LPC). Similarly, gentamicin stimulated the incorporation of [14C]-choline into PC and SM in the order of 300% and 172%, respectively, but not into LPC as compared to control cells. In addition, gentamicin also stimulated the incorporation of [14C]-choline into cytidine diphosphocholine (CDP-choline). However, the endocytosis of [14C]-PC-LDL was lower in cells incubated with gentamicin than in control cells. Thus, exogenously derived PC on LDL does not contribute to the increased cellular levels of PC in PT cells incubated with gentamicin. The activity of cytidine triphosphate (CTP):phosphocholine cytidyltransferase was moderately lower in cells incubated with gentamicin as compared to control. By contrast, the activity of phospholipase A1 and phospholipase C was twofold lower in cells incubated with gentamicin for 21 days as compared to control. Thus, increased incorporation of [14C]-acetate and [14C]-choline into PC in cells incubated with gentamicin may not only be due to increased endogenous synthesis but to decreased catabolism of newly synthesized PC. We conclude that gentamicin impairs the lysosomal catabolism of PC, leading to its accumulation in PT cells. This phenomenon may be an indication of gentamicin-induced nephrotoxicity in man.
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PMID:Gentamicin-induced alterations in phospholipid metabolism in cultured human proximal tubular cells. 285 67

Phospholipase activity in the lysosomes of the protozoan Tetrahymena pyriformis strain NT-1 was studied using phospholipids radioactively labeled in the fatty acid moieties. Lysosomal homogenates showed high phospholipase activity with an acidic pH optimum. Unlike the phospholipases in rat liver lysosomes, almost all activity was recovered from the membranous fraction of the lysosomes. The activity was partially solubilized by treatment of the membranes with a detergent or trypsin. Using specifically labeled phospholipids revealed that phospholipase. A1 and C are predominant in Tetrahymena lysosomes, no appreciable phospholipase A2 or lysophospholipase activity was detected in the fraction. There are two catabolic pathways of the hydrolysis of phospholipid: Hydrolysis is initiated by deacylation at the 1-position by phospholipase A1 and the 2-acyllysophospholipid thus formed is successively attacked by (lyso)phospholipase C; hydrolysis is initiated by cleavage of phosphodiester by phospholipase C and the diacylglycerol thus formed is attacked by lipase. Both pathways give the same end products, free fatty acid and 2-monoacylglycerol. The former pathway might be predominant in Tetrahymena lysosomes under physiological conditions since the pathway is independent of detergent. Phospholipases A1 and C activities were partially released into the medium. At least two different phospholipases C are present in the medium as judged by chromatographic behavior and their substrate specificities.
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PMID:Properties of acid phospholipases in lysosome and extracellular medium of Tetrahymena pyriformis. 308 63

The pathways for degradation of phosphatidylinositol (PI) were investigated in sonicated suspensions prepared from confluent cultures of bovine pulmonary artery endothelial cells. The time courses of formation of 3H-labeled and 14C-labeled metabolites of phosphatidyl-[3H]inositol ([3H]Ins-PI) and 1-stearoyl-2-[14C] arachidonoyl-PI were determined at 37 degrees C and pH 7.5 in the presence of 2 mM EDTA with or without a 2 mM excess of Ca2+. The rates of formation of lysophosphatidyl-[3H]inositol ([3H]Ins-lyso-PI) and 1-lyso-2-[14C] arachidonoyl-PI were similar in the presence and absence of Ca2+, and the absolute amounts of the two radiolabeled lyso-PI products formed were nearly identical. This indicated that lyso-PI was formed by phospholipase A1, and phospholipase A2 was not measurable. In the presence of EDTA, [14C]arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI paralleled release of glycerophospho-[3H]inositol ([3H]GPI) from [3H]Ins-PI. Formation of [3H]GPI was inhibited by treatment with the specific sulfhydryl reagent, 2,2'-dithiodipyridine, and this was accompanied by an increase in [3H]Ins-lyso-PI. In the presence of Ca2+, [14C] arachidonic acid release from 1-stearoyl-2-[14C]arachidonoyl-PI was increased 2-fold and was associated with Ca2+-dependent phospholipase C activity. Under these conditions, [3H]inositol monophosphate production exceeded formation of [14C]arachidonic acid-labeled phospholipase C products, diacylglycerol plus monoacylglycerol, by an amount that was equal to the amount of [14C]arachidonic acid formed in excess of [3H]GPI. Low concentrations of phenylmethanesulfonyl fluoride (15-125 microM) inhibited Ca2+-dependent [14C]arachidonic acid release, and the decrease in [14C] arachidonic acid formed was matched by an equivalent increase in 14C label in diacylglycerol plus monoacyclglycerol. These data supported the existence of two pathways for arachidonic acid release from PI in endothelial cells; a phospholipase A1-lysophospholipase pathway that was Ca2+-independent and a phospholipase C-diacylglycerol lipase pathway that was Ca2+-dependent. The mean percentage of arachidonic acid released from PI via the phospholipase C-diacylglycerol lipase pathway in the presence of Ca2+ was 65 +/- 8%. The mean percentage of nonpolar phospholipase C products of PI metabolized via the diacylglycerol lipase pathway to free arachidonic acid was 28 +/- 3%.
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PMID:Ca2+-dependent and Ca2+-independent pathways for release of arachidonic acid from phosphatidylinositol in endothelial cells. 311 76


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