Activation of phospholipase A2 by carbon tetrachloride in isolated rat hepatocytes.
Freshly isolated rat hepatocytes were exposed to carbon tetrachloride (CCl4) for periods up to 4 hr. Phospholipase A2 activity of these preparations was determined by measuring either the release of [3H]arachidonic acid from cellular phospholipids prelabeled with [3H]arachidonic acid or by measuring the formation of [14C]lysophosphatidylethanolamine from cellular lipids prelabeled with [14C]ethanolamine. Through the use of hexane-partition extraction and thin-layer chromatographic analysis of hepatocyte lipid extracts it was found that CCl4 stimulated phospholipase A2 activity in a dose- and time-dependent manner. Carbon tetrachloride at concentrations of 0.23 to 1.3 mM produced a 1.4- to 5.3-fold increase in phospholipase activity which was initiated within 30-60 min of incubation at 37 degrees. The role of phospholipase activation as a secondary mechanism of CCl4-induced hepatocyte injury is discussed.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004789:Enzyme Activation; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010740:Phospholipases / Q000032:analysis*; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D004983:Ethanolamines; D016718:Arachidonic Acid; D019856:Ethanolamine; D002251:Carbon Tetrachloride; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2