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

---

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

Phospholipase C (lecithinase or phosphatidylcholine phosphorylase) catalyzes the hydrolysis of lecithin into phosphorylcholine and 1,2-diglyceride. Bacterial production of phospholipase C may damage reproductive tract tissues by both direct and indirect mechanisms. Use of the synthetic substrate p-nitrophenylphosphorylcholine phospholipase C activity was determined in 204 isolates representative of those found in female genital tract. Multiple aerobic (28%) and anaerobic (28%) reproductive tract microorganisms showed phospholipase C activity. Phospholipase C-producing isolates included strains of Bacteroides fragilis, B. bivius, B. thetaiotaomicron, Gardnerella vaginalis, and group B streptococcus. Phospholipase C activity was heterogenous; not all isolates that belong to a particular species showed activity. Phospholipase C production may be a possible virulence factor produced by a number of microflora commonly implicated in various reproductive tract infections or conditions, as well as in some instances of preterm birth.
...
PMID:Phospholipase C activity in microorganisms associated with reproductive tract infection. 199 22

The hormonal control of glycogen synthase and phosphorylase interconversion was investigated in hepatocytes isolated from lean and genetically obese (fa/fa) rats. In cells from obese animals, the inactivation of synthase by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), phospholipase C, vasopressin and the alpha 1-adrenergic agonist phenylephrine was markedly impaired, and the property of PMA to counteract phosphorylase activation by phenylephrine was attenuated. The maximal response of phosphorylase activation to phenylephrine and vasopressin was increased in obese-rat hepatocytes, but the sensitivity to these hormones was similar to that in lean-rat hepatocytes. These observations indicate that the defect in protein kinase C that we reported previously in heart of insulin-resistant fa/fa rats [van de Werve, Zaninetti, Lang, Vallotton & Jeanrenaud (1987) Diabetes 36, 310-319] is probably also expressed in liver.
...
PMID:Altered regulation of glycogen metabolism by vasopressin and phenylephrine in hepatocytes from insulin-resistant obese (fa/fa) rats. Role of protein kinase C. 211 21

The activation of phosphoinositide-specific phospholipase C by ethanol was compared in hepatocytes isolated from ethanol-fed rats and from pair-fed control animals. Ethanol (100-300 mM) caused a dose-dependent transient increase in cytosolic free Ca2+ levels in indo-1-loaded hepatocytes from both groups of animals. The rate of Ca2+ increase was similar in hepatocytes from control and ethanol-fed rats, but the decay of the Ca2+ increase was somewhat slower in the latter preparation. The ethanol-induced Ca2+ increase caused activation of glycogen phosphorylase, with 50% response at 50 mM-ethanol and a maximal response at 150-200 mM-ethanol, not significantly different in hepatocytes from control and ethanol-fed animals. Ins(1,4,5)P3 formation in response to ethanol (300 mM) or vasopressin (2 nM or 40 nM) was also similar in the two preparations. It is concluded that long-term ethanol feeding does not lead to an adaptive response with respect to the ethanol-induced phospholipase C activation in rat hepatocytes. The ability of ethanol in vitro to decrease membrane molecular order in liver plasma membranes from ethanol-fed and control rats was measured by e.s.r. Membranes from ethanol-fed animals had a significantly lower baseline order parameter compared with control preparations (0.313 and 0.327 respectively), indicative of decreased membrane molecular order. Addition of 100 mM-ethanol significantly decreased the order parameter in control preparations by 2.1%, but had no effect on the order parameter of plasma membranes from ethanol-fed rats, indicating that the plasma membranes had developed tolerance to ethanol, similar to other membranes in the liver. Thus the membrane structural changes associated with this membrane tolerance do not modify the ethanol-induced activation of phospholipase C. The transient activation of phospholipase C by ethanol in hepatocytes may play a role in maintaining an adaptive phenotype in rat liver.
...
PMID:Phospholipase C activation by ethanol in rat hepatocytes is unaffected by chronic ethanol feeding. 217 85

Stimulation of P2-purinergic receptors by ATP resulted in activation of phosphorylase, which was associated with marked production of inositol trisphosphate (Ins-P3), in rat hepatocytes. ATP also inhibited forskolin-induced accumulation of cAMP in the presence of a phosphodiesterase inhibitor. On the contrary, adenosine or AMP never inhibited the cAMP accumulation, but increased hepatocyte cAMP; the stimulation was antagonized by a methylxanthine. Thus, P1-purinergic receptors are linked to adenylate cyclase in a stimulatory fashion in hepatocytes. Various kinds of purine nucleotides stimulating P2-receptors can be divided into two groups on the basis of their relative abilities to stimulate Ins-P3 production and to inhibit cAMP accumulation; the first group including adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ADP, 5-adenylyl imidodiphosphate, GTP, and guanosine 5'-O-(3-thiotriphosphate) has an efficacy similar to that of ATP, and the second group of nucleotides including alpha, beta-methyleneadenosine 5'-triphosphate, beta, gamma-methyleneadenosine 5'-triphosphate (App(CH)2)p), and GDP exerts considerable inhibitory effects on cAMP accumulation, but only slight effects on inositol lipid metabolism. Treatment of hepatocytes with islet-activating protein, pertussis toxin, blocked the nucleotide-induced inhibition of cAMP accumulation, but exerted only a small effect on Ins-P3 production. In membranes prepared from hepatocytes, forskolin-stimulated adenylate cyclase was inhibited by GTP. This GTP-induced inhibition of the enzyme was susceptible to islet-activating protein and dependent on the concentration of ATP (or its derivatives, ATP gamma S or App(CH2)p). It is concluded that there are two types of P2-purinergic receptors: one is linked to adenylate cyclase via an inhibitory guanine nucleotide regulatory protein (Gi) and the other is linked to phospholipase C.
...
PMID:P2-purinergic receptors are coupled to two signal transduction systems leading to inhibition of cAMP generation and to production of inositol trisphosphate in rat hepatocytes. 244 92

In rat liver prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2), released from non-parenchymal cells, have been implicated as mediators of the enhancement of glucose and lactate output from parenchymal cells caused by sympathetic nerve stimulation [Iwai, M. et al. (1988) Eur. J. Biochem. 175, 45-50]. In isolated rat hepatocytes PGF2 alpha, of which 75% were degraded within 10 min, but not the TXA2 analogue U46619 increased inositol 1,4,5-trisphosphate (IP3), glycogen phosphorylase a activity and glucose output like noradrenaline and vasopressin; cyclic AMP remained unaltered. The maximal increase in IP3 was reached within 20 s and in phosphorylase activity as well as glucose release within 1 min. The results indicate that only PGF2 alpha but not TXA2 can play a role as a direct mediator of the sympathetic metabolic nerve actions in rat liver and that hepatocytes contain also stimulatory prostaglandin receptors linked to phospholipase C in addition to the inhibitory receptors linked to adenylate cyclase known thus far.
...
PMID:Direct activation by prostaglandin F2 alpha but not thromboxane A2 of glycogenolysis via an increase in inositol 1,4,5-trisphosphate in rat hepatocytes. 255 Dec 82

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.
...
PMID:The hormone-sensitive hepatic Na+-pump. Evidence for regulation by diacylglycerol and tumor promoters. 302 43

The short-term effects of ethanol on calcium homeostasis were studied in isolated hepatocytes. Ethanol caused a rapid transient activation of phosphorylase not associated with changes in cAMP levels which peaked after 20-30 s and declined slowly over a period of 5-10 min. Maximal activation was found with 200 mM ethanol, and a significant effect was observed at 25 mM ethanol. Similar effects were induced by other organic solvents and by halothane, with more hydrophobic agents being effective at lower concentrations. In hepatocytes loaded with the intracellular calcium indicator quin2, the addition of ethanol caused a transient increase in cytosolic free calcium, with a kinetic pattern compatible with its involvement in the activation of phosphorylase. Pretreatment of the hepatocytes with phenylephrine or vasopressin to deplete the hormone-sensitive calcium pools in the cells prevented the ethanol-induced calcium mobilization. In 32P-labeled hepatocytes addition of ethanol caused a small (5-7%) decrease in the level of [32P]phosphatidylinositol 4,5-bisphosphate and a 10-15% increase in [32P]phosphatidylinositol 4-phosphate and [32P]phosphatidic acid. In hepatocytes labeled with myo-[3H]inositol, ethanol induced a 50-100% increase in the levels of inositol 1,4,5-trisphosphate, inositol 1,3,4-trisphosphate, and inositol bisphosphate. The changes in the inositol 1,4,5-trisphosphate level due to ethanol paralleled the time course of the elevation of cytosolic free calcium levels and activation of phosphorylase a. The effects of ethanol were comparable to those of a physiologic (1 nM) dose of vasopressin; however, unlike with vasopressin, the inositol phosphates and cytosolic calcium levels declined to basal levels 2 min after the addition of ethanol. These results indicate that ethanol, in common with calcium-mobilizing hormones, activates hormone-sensitive phosphoinositide-specific phospholipase C. The resulting changes in inositol 1,4,5-trisphosphate can account for the mobilization of intracellular calcium and the consequent activation of phosphorylase by ethanol.
...
PMID:Ethanol-induced mobilization of calcium by activation of phosphoinositide-specific phospholipase C in intact hepatocytes. 302 63

Incubation of hepatocytes with the protein kinase C activator and tumour promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) produced a time- and concentration-dependent inactivation of glycogen synthase, but no change in phosphorylase. The same rate and extent of inactivation occurred in hepatocytes depleted of Ca2+ by treatment with the Ca2+ chelator EGTA. When hepatocytes were treated with the Ca2+-mobilizing hormone vasopressin (10 nM), the rate of glycogen synthase inactivation was similar to that observed with PMA (1 microM). Depletion of intracellular Ca2+ stores with EGTA abolished the ability of vasopressin to mobilize Ca2+ and activate phosphorylase without abolishing its ability to inactivate glycogen synthase and increase 1,2-diacylglycerol (DAG), the endogenous activator of protein kinase C. Protein kinase C, either in membranes or after partial purification, was shown to be activated in vitro by PMA in the presence of very low concentrations of Ca2+. Exogenous phospholipase C from Clostridium perfringens, at low concentrations, inactivated glycogen synthase and increased DAG without affecting cell Ca2+ or phosphorylase. It is proposed that the inactivation of glycogen synthase elicited by the Ca2+-mobilizing hormones is due, at least in part, to generation of DAG and activation of protein kinase C.
...
PMID:Mechanism of hepatic glycogen synthase inactivation induced by Ca2+-mobilizing hormones. Studies using phospholipase C and phorbol myristate acetate. 309 47

Ethanol causes a transient activation of the phosphoinositide-specific phospholipase C in intact hepatocytes and mimics the action of receptor-mediated agonists [Hoek, Thomas, Rubin & Rubin (1987) J. Biol. Chem. 262, 682-691]. Preincubation of the hepatocytes with phorbol esters which activate protein kinase C prevented this effect of ethanol: phorbol ester treatment inhibited the ethanol-induced phosphorylase activation, the increase in intracellular free Ca2+ concentrations measured in quin 2-loaded hepatocytes, and the changes in concentrations of inositol phosphates, phosphoinositides and phosphatidic acid. Several lines of evidence indicate that these effects were mediated by protein kinase C. Phorbol esters acted in a concentration range where they activate protein kinase C; phorbol esters that do not activate protein kinase C were not effective in inhibiting the effects of ethanol. The permeant diacylglycerol oleoyl-acetylglycerol also inhibited the effects of ethanol, but other diacylglycerols were not effective in the intact cells. The inhibition of ethanol-induced Ca2+ mobilization by phorbol esters was prevented by preincubating the cells with the protein kinase C inhibitors 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H7) and sphingosine. H7 also enhanced the Ca2+ mobilization induced by ethanol in cells that were not pretreated with phorbol esters, indicating that the transient nature of the ethanol-induced Ca2+ mobilization may be due to an activation of protein kinase C caused by the accumulation of diacylglycerol. These data support a model whereby ethanol activates the phosphoinositide-specific phospholipase C, possibly by affecting receptor-G-protein-phospholipase C interactions in the membrane.
...
PMID:Ethanol-induced phospholipase C activation is inhibited by phorbol esters in isolated hepatocytes. 313 25

The effects of neomycin on Ca2+ fluxes and inositol polyphosphates in hepatocytes were investigated since it has been proposed that this antibiotic inhibits inositol 1,4,5-triphosphate formation in fibroblasts [D. H. Carney, D. L. Scott, E. A. Gordon and E. F. LaBelle, Cell 42, 479 (1985)]. In hepatocytes incubated at 1.3 mM extracellular Ca2+ (Ca2+o) neomycin (2 mM) inhibited 45Ca2+ exchange both in the presence or absence of vasopressin. At 1.3 mM Ca2+o, but not at higher concentrations of Ca2+o, the antibiotic (2 mM) inhibited the increase in glycogen phosphorylase a activity observed at late but not at early times after addition of vasopressin. The antibiotic also inhibited the increase in phosphorylase activity caused by the subsequent addition of 1.3 mM Ca2+o to cells previously incubated in the presence of vasopressin and in the absence of added Ca2+o. The concentration of the antibiotic (2 mM) which gave half-maximal inhibition of phosphorylase activation by vasopressin had no effect on the activation of phosphorylase by glucagon or the release of Ca2+ from intracellular stores induced by vasopressin. At a concentration of 10 mM, neomycin caused a 50% inhibition of the formation of [3H]inositol polyphosphates induced by vasopressin. It is concluded that neomycin, at concentrations which inhibit phosphoinositide-specific phospholipase C in other types of cells inhibits the inflow of Ca2+ across the plasma membrane but does not inhibit inositol trisphosphate formation in hepatocytes.
...
PMID:Evidence that neomycin inhibits plasma membrane Ca2+ inflow in isolated hepatocytes. 325 17


1 2 3 Next >>

---