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)

Diglycerides derived from the phospholipase C-mediated hydrolysis of phosphoinositides are implicated as important mediators of agonist-induced responses, including the stimulation of cell division. alpha-Thrombin-stimulated proliferation of fibroblasts is associated with a sustained increase in cellular diglycerides, while the hydrolysis of phosphoinositides is transient (Wright, T. M., Rangan, L. A., Shin, H. S., and Raben, D. M. (1988) J. Biol. Chem. 263, 9374-9380). A rigorous assessment of this apparent discrepancy requires an analysis of the molecular species of the lipids involved. In this report, we have analyzed the molecular species of 1,2-diglycerides present in quiescent and alpha-thrombin-stimulated IIC9 Chinese hamster embryo fibroblasts. The molecular species profiles of the stimulated diglycerides were compared to the profiles of molecular species contained in cellular phospholipids. We demonstrate that 1) stimulation of IIC9 cells by alpha-thrombin results in an increase in the levels of diglyceride molecular species already present in control, quiescent cultures, without the addition of new species or the complete loss of existing species; 2) the diglycerides present in control cultures as well as in cultures stimulated with alpha-thrombin are all ester-linked; and 3) while the phosphoinositides contribute a significant proportion of the diglycerides generated 15 s following alpha-thrombin addition, phosphatidylcholine contributes most of the diglycerides generated after 5 min and 1 h.
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PMID:Molecular species analysis of 1,2-diglycerides stimulated by alpha-thrombin in cultured fibroblasts. 254 85

We have previously shown in intact human erythrocytes that both the plasma membrane Ca2+ pump activity and its phosphorylation can be increased by phorbol-12-myristate 13-acetate (PMA), a known stimulator of protein kinase C. These effects were inhibited by high doses of adriamycin (L. C. Wright et al., 1993, Arch. Biochem. Biophys. 306, 277-284). We now show that low doses of adriamycin (ADR) (maximum effect at 10 microM for 1-6 min) decrease the amplitude of the intracellular calcium ([Ca2+]i) transient induced by 2.5 microM CaCl2 and 10 microM A23187 in intact human erythrocytes. This is reflected by a parallel increase in Ca(2+)-ATPase activity in plasma membranes isolated from pretreated intact cells. When 10 microM ADR and 1 microM PMA were combined the effects were additive, with a maximum decrease in the Ca2+ transient amplitude of 50%. A similar effect was seen on the Ca(2+)-ATPase activities in isolated membranes. In erythrocytes labeled with [32P]orthophosphate 10 microM ADR induced a 1.5-fold increase in the phosphorylation of the Ca2+ pump and when combined with 1 microM PMA the phosphorylation was greatly enhanced (2.3 times that induced by PMA alone). ADR alone and in combination with PMA was found to decrease both 32P labeling and lipid phosphate content of phosphatidylinositol 4,5-bisphosphate (PIP2). This was accompanied by an increase in the amount of 1,2-diacylglycerol formed in response to 10 microM ADR. We conclude that low doses of ADR are able to stimulate the breakdown of 6-13% of erythrocyte PIP2 by phospholipase C at an intracellular calcium concentration of 2.5 microM, normally regarded as below threshold for phospholipase C activation in erythrocytes. The diacylglycerol formed appears to stimulate protein kinase C to activate the Ca2+ pump and enhance its phosphorylation and Ca2+ efflux in intact human erythrocytes.
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PMID:Regulation of the activity and phosphorylation of the plasma membrane Ca(2+)-ATPase by adriamycin in intact human erythrocytes. 764 72