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)

Histologic and clinical improvement of sun-exposed skin following topical treatment with retinoic acid has been reported. Daily application of retinoic acid typically results within 2-5 d in an erythematous scaling reaction, which lessens with continued usage. The cellular, immunologic, and biochemical basis of this retinoid reaction and its role in the repair of photodamaged skin are not known. To investigate the retinoid reaction in man, we have treated non-sun-exposed skin with 0.1% retinoic acid cream (Retin-A, Ortho Pharmaceutical Corporation, Raritan, NJ) under occlusion for 4 d to induce erythema and then examined changes in 1) histology, 2) expression of cell-surface molecules, 3) the enzymes and second messengers of the phospholipase C/protein kinase C signal-transduction system, 4) levels of eicosanoids, and 5) levels of interleukin-1 protein and mRNA. These parameters were chosen for measurement both because they are indicators of epidermal function and previous studies suggest they may be responsive to retinoic acid treatment. Epidermal cell growth as judged by increased epidermal thickness and mitotic figures was significantly increased in retinoic acid-treated skin compared to vehicle-treated controls. Increased numbers of CD4+ T cells accompanied by prominence of dermal dendrocytes in the papillary dermis and focal keratinocyte expression of intercellular adhesion molecule-1 were observed in retinoic acid-treated biopsies. Phosphoinositide-specific phospholipase C activity and 1,2-diacylglycerol content were also elevated in retinoic acid-treated epidermis. Protein kinase C activity was reduced by one third in both the soluble and membrane fraction, suggesting down-regulation. Surprisingly, in view of the inflammatory nature of the retinoid reaction, no increases were observed in arachidonic acid, its metabolites, interleukin-1 alpha, or interleukin-1 beta. To examine the specificity of the retinoid reaction, subjects were treated with the irritant sodium lauryl sulfate, under conditions that resulted in a reaction clinically similar to that observed with retinoic acid. The histologic alterations induced by sodium lauryl sulfate were found to be indistinguishable from those induced by retinoic acid. These data indicate that, although a wide range of cellular and molecular alterations occur in retinoic acid-treated skin, these changes may not be necessarily specific or unique for retinoic acid.
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PMID:Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin. 167 98

Adenosine A1 receptor mediated formation of inosito 1,4,5-trisphosphate (Ins(1,4,5)P3) and accumulation of cytoplasmic Ca2+ ([Ca2+]i) were investigated in DDT1 MF-2 smooth muscle cells. A strong reduction of the adenosine and N6-cyclopentyladenosine (CPA) induced rise in [Ca2+]i was observed after blocking Ca2+ entry across the plasma membrane with LaCl3. This effect of LaCl3 was not observed in the absence of extracellular Ca2+; it was not caused by reduced Ins(1,4,5)P3 formation or changed Ins(1,4,5)P3 induced Ca2+ release, or influenced by temperature. The inhibition of the CPA induced increase in [Ca2+]i by LaCl3 was strongly counteracted in the presence of ortho-vanadate, an inhibitor of plasma membrane Ca2+ ATPase. Ortho-vanadate might also reduce protein tyrosine-phosphate phosphatase activity involved in tyrosine kinase mediated phospholipase C (PLC) activation. However, ortho-vanadate and tyrphostin 25, a tyrosine kinase inhibitor, did not affect the CPA induced formation of Ins(1,4,5)P3. Taken together, these results show a strong contribution of Ca2+ pumping across the plasma membrane to the regulation of [Ca2+]i mediated by adenosine A1 receptors. Na+/Ca2+ exchange only played a minor role in the initial phase of CPA induced Ca2+ metabolism as measured in low Na+ containing solution. The mechanism by which adenosine A1 receptors activate plasma membrane Ca2+ ATPase pumps does not include direct stimulation of pumps, but most likely involves an indirect pathway activated by a rapid increase in [Ca2+]i.
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PMID:Plasma membrane Ca2+ pumping plays a prominent role in adenosine A1 receptor mediated changes in [Ca2+]i in DDT1 MF-2 cells. 881 32

The muscarinic agonist carbachol stimulated phospholipase D (PLD) in rat submandibular gland (RSMG) ductal cells in a time and concentration-dependent manner. This effect was inhibited by chelation of extracellular calcium with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). PLD could also be activated by epinephrine and AlF(4)(-), two polyphosphoinositide-specific phospholipase C (PPI-PLC) activators, and by the phorbol ester o-tetradecanoylphorbol 13-acetate (TPA) which activates protein kinase C (PKC). Ionomycin and thapsigargin only slightly increased PLD activity. Ortho-vanadate, a tyrosine phosphatase inhibitor, also stimulated PLD activity. Both carbachol and o-vanadate increased the formation of inositol phosphates and the tyrosine phosphorylation of at least two proteins (55-60 and 120 kDa). Calphostin C (a PKC inhibitor), U73122 (a PPI-PLC inhibitor) and genistein (a tyrosine kinase inhibitor) blocked the activation of PLD, of PLC and the phosphorylation of tyrosyl residues in response to carbachol and vanadate. Taken together, these results suggest that rat submandibular gland ductal cells express a calcium-dependent PLD activity. This enzyme is regulated by carbachol via a PLC-PKC-tyrosine kinase pathway.
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PMID:Regulation of phospholipase D by muscarinic receptors in rat submandibular ductal cells. 1240 25

Thyroid-stimulating hormone receptor (TSHR) consists of a hormone-binding extracellular subunit and a seven-transmembrane spanning subunit that interacts with the G proteins G(alphas) and G(alphaq). The two subunits, generated by proteolytic cleavage of a single polypeptide chain, are held together by disulphide bridges. The receptor is completely cleaved in thyroid tissue, while in cultured cells (thyrocytes and non-thyroid cells) the cleaved and uncleaved forms coexist. The reasons for these divergent data are not understood. Here we provide an explanation by showing that cleavage depends on cell-cell contacts. An almost complete cleavage was observed in confluent cells, while in sparse cells most of the receptor was in the uncleaved form. We also show that coupling of TSHR to G(alphaq) (as measured by inositolphosphate generation) is markedly reduced when the receptor is not cleaved. In contrast, coupling to G(alphas) [as measured by cyclic adenosine 3',5'-monophosphate (cAMP) synthesis] is unaffected by cleavage of the receptor. These results suggest that the cell-cell contacts are necessary for cleavage of the receptor, which acts as a regulatory step in inositolphosphate production via phospholipase C activation. The latter observation was confirmed using cells that express the uncleavable mutant TSHR-delta50-NET, for which the TSH-stimulated inositolphosphate production was completely abolished.
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PMID:The cleavage of thyroid-stimulating hormone receptor is dependent on cell-cell contacts and regulates the hormonal stimulation of phospholipase c. 1862 27

The perturbation of Ca(2+)-homeostasis in human granulocytes exposed to ortho and non ortho substituted polychlorinated biphenyls (PCB) was investigated. Ortho substituted PCB congeners increased intracellular free calcium, [Ca(2+)]i, in a concentration-dependent manner. The increase in [Ca(2+)]i was inversely proportional to the total surface area of the ortho substituted congeners. The effect of ortho substituted PCB congeners was dependent upon external Ca(2+) and phospholipase C activation, except for a tetra-ortho substituted congener, 2,2',6,6'-TeCB, that was not phospholipase C-dependent. We suppose that PCBs activate phospholipase C which leads to the production of ins(1,4,5)P3. This will release Ca(2+) from intracellular stores and subsequently activation of Ca(2+) release activated Ca(2+) channels (CRAC) in the plasma membrane. It is also possible that PCBs activate CRAC in a more direct manner. Our findings show that ortho substituted PCB congeners stimulate [Ca(2+)]i elevation in human granulocytes, and this could in part account for the effects of PCB on the immune system.
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PMID:Ortho substituted polychlorinated biphenyls elevate intracellular [Ca(2+)] in human granulocytes. 2178 56

Twenty-three Bacillus cereus isolates from food poisoning outbreaks associated with a diarrheal-type syndrome, fourteen foodborne isolates not associated with food poisoning and fifteen isolates from Brazilian soil samples were analyzed for the presence and genetic diversity (by RE-PCR) of the virulence genes ces (emetic toxin, cereulide), plcR-papR (pleiotropic regulator PlcR and peptide PapR), nheA (a component of the NHE complex), bceT (diarrheal enterotoxin bc-D-ENT), gyrB (B subunit of DNA gyrase), cytK-2 (necrotic enterotoxin cytotoxin K-2), and plcA (phosphatidylcholine-specific phospholipase C). Additionally, these isolates were phenotypically characterized for motility, hemolytic and lecithinase activities, as well as HBL enterotoxin production. The group of isolates associated with food poisoning had the highest occurrence of the phenotypically analyzed factors and the most frequent occurrence and highest genetic diversity of the plcR-papR, nheA, bceT, cytK-2, plcA, and gyrB genes. An analysis of molecular variance (AMOVA), in which all loci were analyzed, demonstrated that the genetic variation intragroup of isolates (92%) was significantly higher than that intergroup (8%) (P<0.05). These results were corroborated by an analysis of the genetic differentiation between the groups, which was low/moderate, the result of a high degree of allele sharing. Our results suggest that B. cereus isolates with the potential to cause food poisoning outbreaks do not have a specific genetic profile characterized by the presence of a particular gene or allele among the genes assessed. On the contrary, different combinations of genes encoding virulence factors may be present in different isolates of B. cereus that potentially cause food poisoning outbreaks.
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PMID:RE-PCR variability and toxigenic profile of food poisoning, foodborne and soil-associated Bacillus cereus isolates from Brazil. 2197 57