Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth muscle was made permeable with alpha-toxin and beta-escin. ATPase activity was measured using a phosphoenolpyruvate-pyruvate kinase regenerating system for ATP that was monitored by NADH fluorescence changes, and Ca2+ was measured using fura 2 fluorescence. alpha-Toxin-and beta-escin-treated bundles of cells had a high ATPase activity, which was reduced 80% when exposed to 1% Triton X-100. This Triton-sensitive ATPase activity was increased by approximately 20% when GTP or GTP gamma S was added to the solutions and was of much greater magnitude than the Ca(2+)-activated ATPase associated with contraction. This high membrane ATPase activity will cause a gradient of ATP into and ADP out of the bundle of cells. Thus modulation of this ATPase by G-protein-receptor mechanisms could alter the force at a constant Ca2+ concentration by changing the ADP/ATP ratio within the cells. Measurements of the fura 2 fluorescence ratio (340/380) in alpha-toxin-treated bundles of cells following sudden changes in extracellular Ca2+ showed that the cells were not freely permeable to Ca EGTA. Similar experiments in beta-escin-treated cells showed the cells to be much more permeable to Ca EGTA. These experiments indicate that great care must be taken in alpha-toxin- and beta-escin-treated fibers to make sure that the intracellular ATP, ADP, and Ca2+ are held constant.
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PMID:Relationship between ATPase activity, Ca2+, and force in alpha-toxin- and beta-escin-treated smooth muscle. 776 79

Alternations of stomach mucose caused by ethanol are in direct correlation with its concentration. ADH in stomach mucose is an efficient barrier against ethanol system toxicity. It stimulates higher secretion of HC1, dilutes protective barrier of mucose and phospholipids in membranes. Inflammatory reaction also participates in the damage of stomach mucose, with a share of products of arachidonic metabolism and free radicals. After ethanol administration the pancreas blood circulation diminishes and resistance in microcirculation increases. This can cause necroses in periphery of lobules. Activated phospholipase C may result in hypersecretion of Ca2+ dependent proteinkinases. Ischemic changes participate in alcohol impairment of pancreas and increase its vulnerability to enzyme attract and free radical reactions. Ethanol excesses may result in diarrhoea, dyspepsia, malnutrition and cause morphologic alternations of intestinal mucose (erosion, hemorrhagia). Absorption of nutrients and vitamins is affected by inhibition of active transport or by decrease of enzyme activity. Ethanol increases mucose permeability, alteres intestinal motility and damages absorption of water and electrolytes. In chronic alcoholics lower villi and changes in bacterial flora are described. The following mechanism of ethanol caused liver injury are observed: acetaldehyde toxicity, change in NAD+/NADH ratio connected with acidosis, cytoskeletal impairment, inhibition of protein synthesis and their secretion, relative perivenular hypoxia, activation of fibrogenesis, increased formation of free radicals with lipid peroxidation and immunological reaction. In hepatocyte there are morphological changes (megamitochondria, etc.) and functional changes (inhibition of glycolysis, inhibition of Krebs cycle and beta oxidation of fatty acids). Ethanol intake activates leukocytes, trombocytes, endothelial and Kupffer cells and their mediators, which result in increase of collagen and proteoglycans synthesis furthermore in fibrotic changes in liver.
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PMID:[Ethanol metabolism and pathobiochemistry of organ damage--1992. III. Mechanisms of damage to the gastrointestinal tract and the liver by ethanol]. 799 16

Angiotensin II is a multifunctional hormone that affects both contraction and growth of vascular smooth muscle cells through a complex series of intracellular signaling events initiated by the interaction of angiotensin II with the AT1 receptor. The cellular response to angiotensin II is multiphasic, involving stimulation within seconds of phospholipase C and Ca2+ mobilization; activation within minutes of phospholipase D, A2, protein kinase C, and MAP kinase; and stimulation after a period of hours of gene transcription and NADH/NADPH oxidase activity. Angiotensin II also activates numerous intracellular tyrosine kinases. In this respect, it shares some aspects of signaling with growth factor and cytokine receptors, including activation of phospholipase C-gamma, src, and ras; association of shc with grb2; and stimulation of the Jak/STAT pathway. The cellular events responsible for this unique series of events may involve receptor movement and the creation of a signaling domain. Elucidation of these pathways is important to our understanding of AT1 receptor function as a final effector of the renin-angiotensin system.
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PMID:Angiotensin II signaling in vascular smooth muscle. New concepts. 903 29

In the pancreatic beta-cell, insulin secretion is stimulated by glucose metabolism resulting in membrane potential-dependent elevation of cytosolic Ca2+ ([Ca2+]c). This cascade involves the mitochondrial membrane potential (delta psi[m]) hyperpolarization and elevation of mitochondrial Ca2+ ([Ca2+]m) which activates the Ca(2+)-sensitive NADH-generating dehydrogenases. Metabolism-secretion coupling requires unidentified signals, other than [Ca2+]c, possibly generated by the mitochondria through the rise in [Ca2+]m. To test this paradigm, we have established an alpha-toxin permeabilized cell preparation permitting the simultaneous monitoring of [Ca2+] with mitochondrially targeted aequorin and insulin secretion under conditions of saturating [ATP] (10 mM) and of clamped [Ca2+]c at substimulatory levels (500 nM). The tricarboxylic acid (TCA) cycle intermediate succinate hyperpolarized delta psi(m), raised [Ca2+]m up to 1.5 microM and stimulated insulin secretion 20-fold, without changing [Ca2+]c. Blockade of the uniporter-mediated Ca2+ influx into the mitochondria abolished the secretory response. Moreover, glycerophosphate, which raises [Ca2+]m by hyperpolarizing delta psi(m) without supplying carbons to the TCA cycle, failed to stimulate exocytosis. Activation of the TCA cycle with citrate evoked secretion only when combined with glycerophosphate. Thus, mitochondrially driven insulin secretion at permissive [Ca2+]c requires both a substrate for the TCA cycle and a rise in [Ca2+]m. Therefore, mitochondrial metabolism generates factors distinct from Ca2+ and ATP capable of inducing insulin exocytosis.
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PMID:Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells. 923 93

Angiotensin (A) II is a potent constrictor as well as growth stimulant of vascular smooth muscle cell caused by activation of AT1 receptor signal transduction systems. There are two major signal systems of AT1 receptor: one leads to an increase in cytosolic free calcium levels causing smooth muscle contraction which may result in high blood pressure, and the other leads to smooth muscle proliferation and inflammation which may result in atherosclerosis. AT1 receptor activation induces phosphinositide hydrolysis by phospholipase C and creates an inositol phosphate, which release calcium from cytosolic calcium pools. Cytosolic calcium can also be elevated by activation of calcium channel via a link between AT1 receptor and a G protein. Protein phosphorylation triggered by AT1 receptor is important for cell growth, in which tyrosine kinase, serine/threonine kinase and protein kinase C are involved. Free radicals are generated by NADH/NADPH oxidase in response to AT1 receptor activation, causing expression of genes leading to atherosclerosis. On the other hand, activation of AT2 receptor is shown to play a role of lowering blood pressure. Some phosphatases and NO/cyclic GMP would be involved in the mechanism. In renal vasculature, endothelium dependent epoxygenase products are synthesized by AT2 receptor stimulation causing vasorelaxation. In summary, AT1 receptor signals are vasopressive and evoke atherosclerosis, whereas AT2 receptor signals may possibly be vasodilatory.
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PMID:[Signal transduction systems of angiotensin II receptors]. 1036 37

Insulin secretion is under multifactorial control by glucose and neurohumoral factors like acetylcholine (ACH), which activate the Ca2+/phospholipase C signaling pathway. All insulin secretagogues elevate cytosolic free Ca2+ ([Ca2+]i) that is central to the stimulation of insulin secretion. The actions of ACH on [Ca2+]i are glucose dependent but the metabolic steps involved are only partly understood. Here we have characterized the metabolic steps by which glucose exerts its synergistic effects on ACH-linked Ca2+-signals. [Ca2+]i was measured in single fura-2 loaded beta-cells. The ACH analog carbachol (3 microM) caused rise in [Ca2+]i that was strongly dependent on the extracellular glucose concentration ranging from 0-10 mM. Iodoacetate, which blocks glycolysis, thereby preventing the generation of NADH and ATP from glucose metabolism, and rotenone or antimycin, which inhibit complex 1 and 2 of the mitochondrial respiratory chain, respectively, inhibited in glucose (6 mM) the carbachol-induced Ca2+ signal to a similar extent as glucose deprivation. This demonstrates that glucose metabolism and generation of ATP through oxidative phosphorylation of energy rich substrates like NADH and FADH2 are required for carbachol-induced Ca2+ signals. While sodium arsenate, which prevents net glycolytic production of ATP without inhibiting glycolysis, had no significant effect on the carbachol-induced Ca2+-signal, the mitochondrial pyruvate transport inhibitor alpha-cyano-4-hydroxycinnamate and the Krebs cycle inhibitor monofluoroacetate strongly suppressed the rise in [Ca2+]i elicited by carbachol. While pyruvate was ineffective, methyl pyruvate, a membrane-permeant pyruvate analog, and alpha-ketoisocaproate in combination with glutamine, which are both substrates for mitochondrial ATP production, could restore the carbachol-induced Ca2+ signal in glucose-free medium. These data demonstrate for the first time that Krebs cycle metabolism of glucose and ATP formation through oxidative phosphorylation is critical for the glucose dependency of ACH-linked Ca2+-signals in mouse beta-cells, and they suggest that mitochondrial metabolism plays a key role in the interactive regulation of beta-cells by neurohumoral factors activating the Ca2+/phospholipase C signaling pathway.
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PMID:Energetic requirement of carbachol-induced Ca2+ signaling in single mouse beta-cells. 1108 37

Disulfide-thiol interchange proteins with hydroquinone (NADH) oxidase activities (designated NOX for plasma membrane-associated NADH oxidases) occur as extrinsic membrane proteins associated with the plasma membrane at the outer cell surface. The cancer-associated NOX protein, designated tNOX, has been cloned. The 34-kDa plasma membrane-associated form of the protein contains no strongly hydrophobic regions and is not transmembrane. No myristoylation or phosphatidylinositol anchor motifs were discovered. Evidence for lack of involvement of a glycosylphosphatidylinositol-linkage was derived from the inability of treatment with a phosphatidylinositol-specific phospholipase C or with nitrous acid at low pH to release the NOX protein from the surface of HeLa cells or from plasma membranes isolated from HeLa cells. Binding of NOX protein to the plasma membrane via amino acid side chain modification or by attachment of fatty acids also is unlikely based on use of specific fatty acid antisera to protein bound fatty acids and as a result of binding to the cancer cell surface of a truncated form of recombinant tNOX. Incubation of cells or plasma membranes with 0.1 M sodium acetate, pH 5, at 37 degrees C for 1 h, was sufficient to release tNOX from the HeLa cell surface. Release was unaffected by protease inhibitors or divalent ions and was not accelerated by addition of cathepsin D. The findings suggest dissociable receptor binding as a possible basis for their plasma membrane association.
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PMID:Surface NADH oxidase of HeLa cells lacks intrinsic membrane binding motifs. 1148 99

Microsomal membranes from potato tubers were treated with a phospholipase C extracted from Bacillus cereus. A positive correlation could be observed between the hydrolysis of membranous phospholipids and the decrease of the NADH-cytochrome c reductase activity. Addition of total lipid or phospholipid micelles to phospholipase C-treated microsomes partially restored the NADH-cytochrome c reductase activity, thus proving the lipid-dependence of this enzyme.
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PMID:Regulation by Lipids of Plant Microsomal Enzymes: II. LIPID DEPENDENCE OF THE NADH-CYTOCHROME c REDUCTASE OF POTATO TUBERS. 1666 41

Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In the current studies we have examined gene expression in B. pseudomallei in an animal model of acute melioidosis using whole-genome microarrays. Gene expression profiles were generated by comparing transcriptional levels of B. pseudomallei-expressed genes in infected hamster organs including liver, lung, and spleen following intraperitoneal and intranasal routes of infection to those from bacteria grown in vitro. Differentially expressed genes were similar in infected livers irrespective of the route of infection. Reduced expression of a number of housekeeping genes suggested a lower bacterial growth rate during infection. Energy production during growth in vivo involved specific biochemical pathways such as isomerization of 3-phosphoglycerate, catabolism of d-glucosamine and inositol, and biosynthesis of particular amino acids. In addition, the induction of genes known to be involved in oxidative phosphorylation including ubiquinol oxidase, ferredoxin oxidoreductase, and formate dehydrogenase enzymes suggested the use of alternative pathways for energy production, while the expression of genes coding for ATP-synthase and NADH-dehydrogenase enzymes was reduced. Our studies have identified differentially expressed genes which include potential virulence genes such as those for a putative phospholipase C and a putative two-component regulatory system, and they have also provided a better understanding of bacterial metabolism in response to the host environment during acute melioidosis.
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PMID:Genome-wide expression analysis of Burkholderia pseudomallei infection in a hamster model of acute melioidosis. 1698 21


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