The effect of adriamycin on glycerolphosphate acyltransferase and lipid metabolism in rat hepatocytes in monolayer culture.
Total and mitochondrial glycerolphosphate acyltransferase activities were measured after 24 hr exposure of rat hepatocytes to Adriamycin. Both activities decreased with increasing concentrations of Adriamycin. The activity of the microsomal glycerolphosphate acyltransferase, which was determined from the difference between the total and mitochondrial enzyme activity, also decreased with increasing drug concentration. The effect on glycerolphosphate acyltransferase was specific as there was no change in lactate dehydrogenase or cytochrome oxidase activity in this time period. Adriamycin did not inhibit mitochondrial glycerolphosphate acyltransferase activity in vitro. After 24 hr exposure of hepatocytes to Adriamycin no change was observed in the biosynthesis of phosphatidylcholine or triacylglycerol. Secretion of lipid into the medium was measured over the subsequent 24 hr. There was a significant reduction in very low density lipoprotein secretion as measured by triacylglycerol secretion from cells incubated with 5 microM Adriamycin. Cells were damaged by the 48 hr exposure to 1 microM and higher concentrations of Adriamycin as evidenced by a fall in lactate dehydrogenase activity in these cells. The secretion of lysophosphatidylcholine, as measured by the incorporation of [3H]glycerol into medium lysophosphatidylcholine, was significantly increased when cells were incubated with 5 microM Adriamycin. The results are discussed in relation to the effect of Adriamycin on hepatic lipid metabolism and the cardiotoxicity of the drug.
Mangiapane
E H
EH
Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.
D000818:Animals; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D008079:Lipoproteins, VLDL; D010713:Phosphatidylcholines; D014280:Triglycerides; D004317:Doxorubicin; D005992:Glycerol-3-Phosphate O-Acyltransferase