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 mechanisms by which ethanol inhibits hepatocyte proliferation have been a source of some considerable investigation. Our studies have suggested a possible role for tissue transglutaminase (tTG) in this process. Others have shown that tTG has two distinctly different functions: it catalyzes protein cross-linking, which can lead to apoptosis and enhancement of extracellular matrix stability, and it can function as a G protein (Galpha(h)). Under that circumstance, we speculated that the cross-linking activity would be decreased and that it would function to enhance hepatocyte proliferation in response to adrenergic stimulation. Ethanol treatment inhibited hepatocyte proliferation and led to enhanced tTG cross-linking activity, whereas treatment of hepatocytes with an alpha1 adrenergic agonist, phenylephrine, enhanced hepatocyte proliferation while decreasing tTG cross-linking. However, phenylephrine treatment of several hepatoma cell lines had no effect on cellular proliferation or tTG cross-linking activity, and of note, Northern blot analysis demonstrated that whereas primary hepatocytes had high levels of the alpha1beta adrenergic receptor (alpha1BAR) mRNA, the hepatoma cell lines did not have this mRNA. When the Hep G(2) cell line was stably transduced with an expression vector containing the alpha1BR cDNA, the cell line responded to phenylephrine treatment with enhanced proliferation and with decreased tTG cross-linking activity. Ethanol treatment of the alpha1BAR-transfected cells suppressed the phospholipase C-mediated signaling pathways, as detected in the phenylephrine-induced Ca(2+) response. These results suggest that phenylephrine stimulation of hepatocyte proliferation appears to be occurring through the alpha1BAR, which is known to be coupled with the tTG G protein moiety, Galpha(h), and that tTG appears to play a significant role in either enhancing or inhibiting hepatocyte proliferation, depending on its cellular location and on whether it functions as a cross-linking enzyme or a G protein.
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PMID:Roles of tissue transglutaminase in ethanol-induced inhibition of hepatocyte proliferation and alpha 1-adrenergic signal transduction. 1080 82

Ethanol and other drugs of abuse increase synaptic dopamine levels; however, little is known about how ethanol alters dopaminergic signaling. We have reported that ethanol induces translocation of delta and epsilon protein kinase C (PKC) in neural cells in culture. Using NG108-15 and Chinese hamster ovary cell lines that express the dopamine D2 receptor (D2R), we show here that the D2R agonist R(-)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide (NPA) also causes translocation of delta and epsilon PKC to the same sites as ethanol-induced translocation. D2R agonist and ethanol-induced translocation of delta and epsilon PKC share a common pathway that is blocked by pertussis toxin and requires phospholipase C (PLC) activity. These data suggest that both D2R agonists and ethanol activate PLC via a trimeric G protein leading to production of diacylglycerol with subsequent activation and translocation of delta and epsilon PKC. Moreover, ethanol and NPA, when present together at low concentrations that alone are ineffective, act synergistically to cause translocation of delta and epsilon PKC. Our data suggest that ethanol causes translocation of delta and epsilon PKC but cells expressing the D2R, such as neurons in the nucleus accumbens, may be particularly sensitive to low concentrations of ethanol.
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PMID:Ethanol acts synergistically with a D2 dopamine agonist to cause translocation of protein kinase C. 1112 36

To understand the underlying mechanism of ethanol in tonic contraction, the effect of ethanol on phospholipase A(2) and phospholipase C activities and the effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric smooth muscle were tested. Circular muscle strips (2.0 x 0.2 cm) obtained from the fundus of cat stomach were used to measure isometric contraction. Ethanol elicited tonic contraction and activated phospholipase A(2) activity in a dose-dependent manner. Phospholipase A(2) inhibitors, manoalide (0.1--10 microM) and oleyloxyethyl phosphorylcholine (1--10 microM), significantly inhibited ethanol-induced contraction. Furthermore, 342 mM ethanol-induced contraction was significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10--100 microM) and indomethacin (10--100 microM), but not by lipoxygenase inhibitors. On the other hand, phospholipase C inhibitors had no effect on ethanol-induced contraction, indicating that phospholipase C is not involved in ethanol-induced contraction. It is suggested from the above results that ethanol-induced contraction in cat gastric smooth muscle is, in part, mediated by phospholipase A(2) and cyclooxygenase pathways.
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PMID:The involvement of phospholipase A(2) in ethanol-induced gastric muscle contraction. 1122 4

In the present study, we investigated the effect of raw as well as thermally oxidized sunflower oil (commercially available) on ethanol induced hepatotoxicity. Ethanol was given to animals at a level of 20% and sunflower oil at a level of 15%. Results show higher activity of plasma aspartate transaminase (AST) and alkaline phosphatase (ALP) and also higher levels of plasma and tissue cholesterol, phospholipids and triglycerides both in alcohol+raw as well as thermally oxidized oil groups. The level of cholesterol and triglycerides increased significantly in the liver of rats given alcohol alone, alcohol and raw as well as thermally oxidized oil but the level of phospholipids decreased. The activity of phospholipase A and phospholipase C in liver was found to be increased significantly in alcohol alone, alcohol+oil groups as compared to control group. Histopathological changes in the liver of alcohol and alcohol+oil groups were in good correlation with biochemical parameters. The liver samples of alcohol administered rats showed both microvesicular and macrovescicular type of fatty changes, where as alcohol+oil fed groups showed inflammatory cell infiltrate in the portal triad, microvesicular and macrovesicular type of fatty changes and feathery degeneration of hepatocytes. Studies on the phospholipid fatty acid composition in the liver showed the presence of a number of fatty acids in the alcohol and oil treated groups, which are not present in the control group. The results obtained thus indicate hepatotoxic and hyperlipidaemic effects of alcohol and oil given together.
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PMID:Toxic effects of sunflower oil on ethanol treated rats. 1227 Jul 41

Ethanol-induced pseudohyphal development in the cells of Candida tropicalis Pk233 was accompanied by the transient accumulation of inositol 1,4,5-trisphosphate (IP3) that occurred at an early growth stage. The concomitant addition of myo-inositol prevented the activation of IP3 accumulation and cancelled pseudohyphal development in the presence of ethanol. The addition of a specific phospholipase C inhibitor, U73 122, inhibited ethanol-induced pseudohyphal transition at the concentrations of subinhibitory levels of cell growth. Pseudohyphal development was also induced by the Ca2+ ionophore, A23 187 in the absence of ethanol. The effect of A23 187 on the development of pseudohyphae was little influenced by myo-inositol, but stimulated by concomitant addition of 12-O-tetradecanoylphorbol 13-acetate. These results suggest that ethanol activated phospholipase C in competition with myo-inositol, and the resulting IP3-Ca2+ and protein kinase C pathways of PI signal transduction may work in pseudohyphal transition.
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PMID:Ethanol-induced pseudohyphal transition in the cells of Candida tropicalis: participation of phosphoinositide signal transduction. 1648 41

DAG derived from phosphatidylcholine (PtdCho) acts as a lipid second messenger. It can be generated by the activation of phospholipase D (PLD) and the phosphatidic acid phosphohydrolase type 2 (PAP2) pathway or by a PtdCho-specific phospholipase C (PtdCho-PLC). Our purpose was to study PtdCho-PLC activity in rat cerebral cortex synaptosomes (CC Syn). DAG production was highly stimulated by detergents such as Triton X-100 and sodium deoxycholate. Ethanol and tricyclodecan-9-yl-xanthate potassium salt decreased DAG generation by 42 and 61%, respectively, at 20 min of incubation. These data demonstrate that both the PLD/PAP2 pathway and PtdCho-PLC contribute to DAG generation in CC Syn. PtdCho-PLC activity remained located mainly in the synaptosomal plasma membrane fraction. Kinetic studies showed Km and Vmax values of 350 microM and 3.7 nmol DAG x (mg protein x h)(-1), respectively. Western blot analysis with anti-PtdCho-PLC antibody showed a band of 66 KDa in CC Syn. Our results indicate the presence of a novel DAG-generating pathway in CC Syn in addition to the known PLD/PAP2 pathway.
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PMID:Coexistence of phosphatidylcholine-specific phospholipase C and phospholipase D activities in rat cerebral cortex synaptosomes. 1671 2

Despite Pseudomonas aeruginosa antibiotic resistance, erythromycin (ERM, a macrolide) at subinhibitory concentration (sub-MIC) reduces its pathogenicity. We assessed ERM effects on P. aeruginosa in cultures containing choline (Ch) without and with 1% ethanol (Et) addition. Ch, as an osmoprotectant, increases the following virulence factors (VIFs): lectins (haemagglutination); proteases (casein and elastin lysis); haemolytic phospholipase C (PLC-H; haemolysis); pyocyanin (pigment o.d.) and autoinducers (violacein bioassay). Ethanol also increases lectins, proteases, pyocyanin, autoinducers and rhamnolipid (RHAL; haemolysis) formation, but reduces Ch-induced PLC and protease (elastase) activities. ERM has been shown to totally suppress the Et-induced VIFs, whereas partially reducing the Ch-induced ones. Unexpectedly, ERM combination with 1% Et dramatically annuls the Ch-induced factors. Et contribution might be attributed to its effect on cell membrane, displaying synergism with ERM, whereas antagonizing Ch osmoprotective potential and shifting gene expression. This information is worth further molecular investigation and clinical consideration for skin infection therapy.
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PMID:Abrogation of the resistance of choline-induced Pseudomonas aeruginosa virulence to sub-MIC erythromycin by ethanol. 1875 42

It is largely accepted that an activation of the dopaminergic system underlies the recreational and convivial effects of ethanol. However, the mechanisms of action of this drug on the dopaminergic neurons are not fully understood yet. In the present study, we have used intracellular electrophysiological techniques (current and single-electrode voltage-clamp) to investigate the actions of ethanol on the gamma-aminobutyric acid (GABA)(B)-mediated inhibitory postsynaptic potentials (IPSPs) in rat midbrain dopaminergic neurons. Ethanol (10-200 mM) augmented, in a concentration-dependent and reversible manner, the amplitude of the GABA(B)-IPSP. In addition, the GABA(B) agonist baclofen generated G-protein-gated inward rectifying K(+) channels (GIRK)-related membrane hyperpolarizations/outward currents that were potentiated by ethanol. The potentiating effect of ethanol persisted in tetrodotoxin (TTX)-treated neurons, suggesting a postsynaptic site of action. These effects of ethanol were not changed by manipulating adenyl cyclase, protein kinases and phospholipase C activity, or by chelating intracellular Ca(2+) with EGTA. Interestingly, the outward current caused by the intracytoplasmatic diffusion of the irreversible G-protein activator GTPgammaS was transiently enhanced by ethanol. Our observations suggest that the action of ethanol occurs on activated GIRK channels downstream of the GABA(B) receptors. These enhancing effects of ethanol on GABA(B)-induced synaptic responses could modulate alcohol intake and the altered mental and motor performance of individuals in an acute intoxicative phase.
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PMID:Ethanol enhances GABAB-mediated inhibitory postsynaptic transmission on rat midbrain dopaminergic neurons by facilitating GIRK currents. 1930 16

Regular alcohol consumption decreases the incidence of myocardial infarction (MI) and improves post-MI survival. It has previously been reported that chronic ethanol exposure induces long-term protection against cardiac ischemia/reperfusion injury, which improves myocardial recovery after MI. Chronic cardioprotection by ethanol requires the activation of myocyte adenosine A1 receptors and sustained intramyocyte translocation of epsilon protein kinase C. A1 receptors activate phospholipase C (PLC). In the present paper, the role of PLC in mediating ethanol's protective effect against ischemia/reperfusion injury is investigated. Isolated hearts from guinea pigs fed 2.5% ethanol in their water for four months were subjected to ischemia/reperfusion. Hearts from ethanol-treated animals showed improved recovery of left ventricular developed pressure compared with controls (61% versus 38% of baseline, respectively; P<0.05) and decreased necrosis, assessed by the release of creatine kinase (263+/-18 U/mL x g dry weight versus 360+/-24 U/mL x g dry weight, respectively; P<0.05). Ethanol protection was abolished by the PLC antagonist, U-73122 (50 nM). These findings suggest that PLC activation is required for ethanol cardioprotection against ischemia/reperfusion injury.
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PMID:Phospholipase C activation is required for cardioprotection by ethanol consumption. 1964 18

Ethanol (164 mm) produced reproducible relaxations in isolated mouse esophageal strips. Hexamethonium (10-500 microm), a ganglionic blocking agent, and lidocaine (10-100 microm), a local anesthetic agent, failed to affect the relaxations induced by ethanol in the mouse esophagus. Although verapamil (10-500 microm), a selective blocker of L-type Ca(2+) channels, failed to affect the relaxations to ethanol, ruthenium red (10-100 microm), a selective blocker of ryanodine receptors (intracellular Ca(2+) channels), and cyclopiazonic acid (1-10 microm), a selective blocker of sarcoplasmic reticulum Ca(2+) ATPase (SERCA), significantly inhibited these relaxations. In addition, tetraethylammonium (10-100 microm), a potassium-selective ion channel blocker and N(omega)-nitro-l-arginine (l-NOARG; 10-500 microm), a specific inhibitor of nitric oxide synthase (NOS), neomycin (10-500 microm), a phospholipase C inhibitor and indomethacine (1-10 microm), a non-selective COX inhibitor, significantly inhibited the relaxations induced by ethanol. In contrast ouabain (10-100 microm), an inhibitor of Na(+)-K(+)-ATPase, failed to cause significant alteration on these relaxations in the same tissue. The results of the present study suggest that the inhibitory effect of ethanol on the mouse esophagus may be direct effect of ethanol on the muscle tissue rather than neuronal effect. In addition, intracellular but not extracellular Ca(2+) may have a role on ethanol-induced relaxations in isolated mouse esophageal strips. Potassium channels and nitric oxide may also have a role on these relaxations. Similarly, phospholypase C and arachidonic acid pathways may contribute the relaxations to ethanol. However Na(+)-K(+)-ATPase may not have a role on relaxations induced by ethanol in the mouse esophagus.
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PMID:Ethanol-induced relaxation of mouse esophagus: subcellular mechanisms. 1973 2


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