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 effects of polyvalent cations (polyamines and aminoglycoside antibiotics) on Ca2+-dependent phosphatidylinositol-specific phospholipase C activity of human amnion tissue were examined. In the presence of 1 mM Ca2+, the hydrolysis of phosphatidylinositol (2 mM) by phospholipase C was increased greatly (240-560% of control) by spermine (0.4 mM), spermidine (1 mM), neomycin (0.1 mM), gentamicin (0.2 mM), kanamycin (0.4 mM) and streptomycin (0.8 mM). Putrescine and cadaverine (0.1-2.0 mM), however, stimulated phospholipase C activity only slightly. The effects of spermidine, spermine and gentamicin on phospholipase C activity were characterized and found to be dependent upon the concentrations of phosphatidylinositol, Ca2+ and the particular polyvalent cation. At low concentrations of phosphatidylinositol and Ca2+ the predominant effect of polyamines and aminoglycosides was to inhibit phospholipase C activity. When the concentrations of phosphatidylinositol and Ca2+ were increased, spermidine, spermine and gentamicin stimulated phospholipase C activity. In the presence of 16 mM Ca2+, however, phospholipase C activity was maximal and was unaffected by either polyamines or aminoglycosides. At all concentrations of Ca2+ examined, the maximal stimulation of phospholipase C activity by a given polyvalent cation occurred at a fixed molar ratio of the particular polyvalent cation to phosphatidylinositol. Polyamines and aminoglycosides appeared to modulate the Ca2+ requirement for phospholipase C activity, but could not substitute completely for Ca2+. The activities of phospholipase A2, diacylglycerol lipase, monoacylglycerol lipase and diacylglycerol kinase in amnion tissue were unaffected by any of the polyvalent cations examined. It is proposed that any in vivo influences (stimulatory or inhibitory) of polyamines and aminoglycosides on amnion phospholipase C activity would depend upon the effective concentrations of Ca2+ and phosphatidylinositol.
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PMID:The effects of polyamines and aminoglycosides on phosphatidylinositol-specific phospholipase C from human amnion. 684 63

Arachidonic acid (the precursor of prostaglandins of the 2-series and related compounds) is released from phosphatidylinositol in a reaction sequence catalyzed by three enzymes, i.e., phospholipase C, diacylglycerol lipase, and monoacylglycerol lipase. Diacylglycerol, an intermediate in this pathway, was found in human amnion tissue. The fatty acid composition of the diacylglycerol fraction of amnion tissue was very similar to that of the phosphatidylinositol fraction. The diacylglycerol content of human amnion tissue obtained during early labor was greater than that of amnion tissue obtained before the onset of labor. These findings are supportive of the proposition that arachidonic acid is released from the phosphatidylinositol of amnion tissue during human parturition.
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PMID:Initiation of human parturition. 705 44

21-day-old rat brain contains a soluble phospholipase C with the ability to hydrolyse phosphatidylcholine. This enzyme has an alkaline pH optima. The results of the DEAE-cellulose fractionation, the pH profile and the Ca2+-dependency suggest that the enzyme may be the same as that responsible for phosphatidylinositol hydrolysis. The activity of the phospholipase C is associated closely with a diacylglycerol lipase. The two enzyme activities could be separated by DEAE-cellulose fractionation, resulting in greater than 100% apparent recovery of the phospholipase C acivity. This phospholipase C activity is not the result of the back reaction of choline phosphotransferase.
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PMID:Phospholipase activities of rat brain cytosol. Occurrence of phospholipase C activity with phosphatidylcholine. 709 92

An assay procedure was developed in which phosphatidyl[2-(3)H]inositol was employed as substrate for the measurement of phosphatidylinositol-specific phospholipase C activity. Employing this assay, phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua was identified and characterized. The specific activity of this enzyme in amnion (4.4 mumol x mg(-1) protein x h(-1)) was three times that in uterine decidua and more than five times that in chorion laeve. No difference was found between the specific activity of phosphatidylinositol-specific phospholipase C in placental amnion and that in reflected amnion. The products of phosphatidylinositol hydrolysis in short-term incubations were stoichiometric amounts of diacylglycerol and inositol-1,2-cyclic-phosphate plus inositol-1-phosphate. After longer periods of incubation, monoacylglycerol also was detected. Diacylglycerol lipase activity also was demonstrated in these tissues. More than 90% of phosphatidylinositol-specific phospholipase C activity of amnion tissue was recovered in the 105,000-g supernatant fraction, and optimal enzymatic activity in vitro was observed at pH 6.5-7.5 in the presence of Ca(2+) (8 mM) and mercaptoethanol (4 mM). Phosphatidylinositol-specific phospholipase C activity was stimulated by fatty acids in low concentrations, but was inhibited by lysophosphatidylcholine and a variety of detergents. No effect of labor on the specific activity of phosphatidylinositol-specific phospholipase C in either fetal membranes or uterine decidua could be detected. The finding of an active phosphatidylinositol-specific phospholipase C activity in human fetal membranes and uterine decidua is complementary to our previous finding of a selective loss of arachidonic acid from phosphatidylinositol of human fetal membranes during labor. The action of phosphatidylinositol-specific phospholipase C, coupled to diacylglycerol lipase action, could provide a mechanism for the release of arachidonic acid for prostaglandin biosynthesis during parturition.
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PMID:Phosphatidylinositol-specific phospholipase C in fetal membranes and uterine decidua. 720 59

1-O-Hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), structurally identical with platelet activating factor, is a potent stimulus for rabbit platelet aggregation and serotonin secretion. AGEPC at concentrations between 10(-10) and 10(-8) M induced stimulation of rabbit platelet synthesis of thromboxane B2. The dose vs. response curve for platelet thromboxane B2 synthesis was displaced slightly towards higher stimulus concentrations compared to [3H]serotonin secretion, with half-maximal concentrations of 2.5 . 10(-9) and 8 . 10(-10) M, respectively. Rates of thromboxane B2 synthesis and secretion were similar with a t 1/2 max of 4.0-4.5 s for both processes. AGEPC induced a decrease in platelet [14C]arachidonic acid in both phosphatidylinositol and phosphatidylcholine, although [14C]arachidonic acid turnover in phosphatidylcholine was not observed below 1 . 10(-8) M AGEPC. Concomitantly, this decrease in phospholipid [14C]arachidonic acid was associated with a marked increase of radiolabel in platelet diacylglycerol and phosphatidic acid 15 s after AGEPC addition, suggesting the possibility of a phospholipase C-diacylglycerol lipase mechanism of fatty acid cleavage. As observed previously with secretion and aggregation, removal of the 2-acetyl group from AGEPC abrogated all capacity of this molecule to stimulate platelet phospholipase. This study indicates that AGEPC (or platelet activating factor) activation of rabbit platelet phospholipase occurs in a time-course and concentration range similar to that required for [3H]serotonin secretion.
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PMID:Activation of rabbit platelet phospholipase and thromboxane synthesis by 1-O-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor). 721 65

Endogenous phospholipid metabolism in stimulated human platelets was studied by phosphorus assay of major and minor components following separation by two-dimensional thin-layer chromatography. This procedure obviated the use of radioactive labels. Extensive changes were found in quantities of phosphatidylinositol (PI) and phosphatidic acid (PA) as a consequence of thrombin or collagen stimulation. Thrombin addition was followed by rapid alterations in the amount of endogenous PI and PA. The decrease in PI was not precisely reciprocated by an increase in PA when thrombin was the stimulus. This apparent discrepancy could be explained by removal of a transient intermediate in PI metabolism, such as diglyceride, formed by PI-specific phospholipase C (Rittenhouse-Simmons, S., J. Clin. Invest.63: 580-587, 1979). Diglyceride would be unavailable for PA formation by diglyceride kinase, if hydrolyzed by diglyceride lipase (Bell, R. L., D. A. Kennerly, N. Stanford, and P. W. Majerus. Proc. Natl. Acad. Sci. U. S. A.76: 3238-3241, 1979) to yield arachidonate for prostaglandin endoperoxide formation. Thrombin-treated platelets also accumulated lysophospho-glycerides. Specifically, lysophosphatidyl ethanolamines accumulated within 15s following thrombin addition. Fatty acid and aldehyde analysis indicated phospholipase A(2) activity, with an apparent preference for diacyl ethanolamine phosphoglycerides. In the case of collagen, these changes occurred concomitantly with aggregation and consumption of oxygen for prostaglandin endoperoxide formation.THESE STUDIES OF ENDOGENOUS PHOSPHOLIPID METABOLISM PROVIDE INFORMATION SUPPORTING THE EXISTENCE OF TWO PREVIOUSLY POSTULATED PATHWAYS FOR LIBERATION OF ARACHIDONIC ACID FROM PLATELET PHOSPHOLIPIDS: (a) the combined action of PI-specific phospholipase C plus diglyceride lipase yielding arachidonate derived from PI; and (b) a phospholipase A(2) acting primarily on diacyl ethanolamine phosphoglyceride.
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PMID:Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophospholipids. 740 Mar 15

We recently proposed a new pathway by which arachidonate is released from platelet phosphatidyl inositol after stimulation by either thrombin or calcium ionophore A23187. The initial step in arachidonate liberation involves hydrolysis of phosphatidyl inositol to form 1,2-diacyglycerol which is subsequently hydrolyzed by a diacyglycerol lipase to liberate arachidonate for the prostaglandin and lipoxygenase pathways. Whether this pathway is unique to platelets or accounts for arachidonate release from other tissues has not been previously studied. Thus we have now investigated arachidonate metabolism in mouse fibrosarcoma cells (HSDM1C1) grown in culture. These cells contain approximately 7.6% of their total phospholipid as phosphatidyl inositol in the resting state (range 6.5-8.3%). When bradykinin (12 microM) is added to the fibrosarcoma cells, there is a rapid depletion of membrane phosphatidyl inositol reaching 62 +/- 8% S.D. of baseline values by 15 seconds, falling to 36 +/- 6% by 15 minutes. The drop in membrane phosphatidyl inositol is accompanied by release of arachidonate and PGE2 into the culture medium. The time course of phosphatidyl inositol breakdown and PGE2 formation supports the idea that phosphatidyl inositol breakdown provides he arachidonate for prostaglandin synthesis in mouse fibrosarcoma cells. Crude extracts of HSDM1C1 cells contained sufficient phosphatidyl inositol-specific phospholipase C activity and diacylglycerol lipase activity to account for arachidonate release in these cells.
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PMID:Bradykinin-stimulated release of arachidonate from phosphatidyl inositol in mouse fibrosarcoma cells. 741 91

To clarify the possible mechanisms regulating prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) synthesis, the effects of gonadotropin-releasing hormone (GnRH) and substance P (SP) on the release of these two prostaglandins were studied in the oocytes of the crested newt, Triturus carnifex. Full-grown oocytes of T. carnifex, freed from follicular cells, were incubated in the presence of GnRH or SP and of the inhibitors of several enzymes involved in the release of arachidonic acid (AA) and in the conversion of AA into PGE2 and PGF2 alpha. In parallel, the same experiments were performed on oocytes with membrane phospholipids labelled with [3H]AA. In addition, the PGE2-9-ketoreductase activity was evaluated through the conversion of [3H]PGE2 into [3H]PGF2 alpha. The results showed that GnRH and SP could regulate prostaglandin synthesis through the activation of phospholipase C and diacylglycerol lipase, and through the modulation of PGE2-9-ketoreductase in the oocytes of T. carnifex. In particular, GnRH enhances the activity of PGE2-9-ketoreductase with a consequent increase in PGF2 alpha, while SP inhibits the enzyme which leads to an increase in PGE2. A similar mechanism could also be hypothesized for other vertebrate species.
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PMID:Amphibian oocyte: a model of a possible regulatory mechanism for prostaglandin E2 and prostaglandin F2 alpha synthesis. 754 11

Membrane phospholipid degradation has been proposed to play a key role in hypoxic-ischemic brain injury. We tested the hypotheses that both nordihydroguaiaretic acid, a phospholipase A2 and lipoxygenase inhibitor, and RHC 80267, a diacylglycerol lipase inhibitor, would decrease the release of [3H]arachidonic acid metabolites from prelabeled cultures of astroglia subjected to combined glucose-oxygen deprivation and that these inhibitors would also decrease astroglial injury during combined glucose-oxygen deprivation. Both nordihydroguaiaretic acid and RHC 80267 significantly inhibited the release of [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. This suggests that two separate enzymic pathways, the phospholipase A2 pathway and the phospholipase C/diacylglycerol lipase pathway, contribute to the release of astroglial [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. However, both of these lipase inhibitors increased astroglial cell death during combined glucose-oxygen deprivation, probably due to inhibition of arachidonic acid release. We speculate that arachidonic acid release may be a mechanism of astroglial self-preservation during combined glucose-oxygen deprivation.
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PMID:Nordihydroguaiaretic acid and RHC 80267 potentiate astroglial injury during combined glucose-oxygen deprivation. 754 17

In the present study, we investigated possible mechanisms behind exogenous phospholipase C-induced glycerol production in irreversibly damaged myocytes. Rat ventricular myocytes were preincubated for 60 min in substrate-free Krebs-Henseleit bicarbonate buffer equilibrated with 95% N2-5% CO2 (37 degrees C, pH = 7.4), resulting in exhaustion of cellular high energy phosphates and loss of rod-shaped morphology. At the end of the preincubation period, the incubation vials were divided into two groups; one receiving 10 mU/ml phospholipase C (PC-PLC), whereas the other received an equivalent volume of buffer (control incubations). Incubation was then continued for another 60 min under 95% air-5% CO2 atmosphere. Samples for measurement of metabolite levels were taken immediately after cell isolation, at the end of the preincubation period and at the end of the normoxic incubation period. During the 60 min incubation period following reoxygenation, glycerol output was markedly higher from PC-PLC treated than from control myocytes. However, the elevated glycerol output from these cells was not accompanied by a simultaneous rise in glycerol-3-phosphate, nor was it inhibited by inclusion of pyruvate in the incubation buffer. On the other hand, glycerol output from PC-PLC treated myocytes was effectively inhibited by a diacylglycerol lipase inhibitor (U-57908, The Upjohn Company). Analysis of cellular lipids revealed a 22% reduction of phospholipid in PC-PLC treated myocytes (P < 0.02), while the content of triacylglycerol, diacylglycerol and unesterified fatty acids increased by 76, 261 and 103%, respectively (P < 0.02). No significant changes were observed for these parameters in control myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phospholipid degradation in hypoxic/reoxygenated cardiomyocytes in response to phospholipase C from Bacillus cereus. 760 7


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