Loss of response of carnitine palmitoyltransferase I to okadaic acid in transformed hepatic cells.
The specific activity of carnitine palmitoyltransferase I (CPT-I) was similar in mitochondria isolated from rat Fao and human HepG2 hepatoma cells and from rat hepatocytes, but almost twofold higher in permeabilized hepatoma cells than in permeabilized hepatocytes. Short-term exposure to okadaic acid induced a ca. 80% stimulation of CPT-I in hepatocytes, whereas no significant response of the enzyme from hepatoma cells was evident. Thus, the high CPT-I activity displayed by hepatoma cells may be reached by hepatocytes upon challenge to okadaic acid. Reconstitution experiments with purified mitochondrial and cytoskeletal fractions showed that the cytoskeleton of hepatocytes produced a more remarkable inhibition of CPT-I than the cytoskeleton of Fao cells. The present data may be explained by a disruption of interactions between CPT-I and cytoskeletal components in tumor cells that may be involved in the okadaic acid-induced activation of hepatic CPT-I as previously suggested.
Velasco
G
G
Department of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University, Madrid, Spain.
Passilly
P
P
Guzmán
M
M
Latruffe
N
N
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002334:Carnitine O-Palmitoyltransferase / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D008114:Liver Neoplasms, Experimental; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D019319:Okadaic Acid / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D019319:Okadaic Acid; D002334:Carnitine O-Palmitoyltransferase