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 permeabi lized hepatoma cells than in permeabilized hepatocytes. Short-term exp osure to okadaic acid induced a ca. 80% stimulation of CPT-I in hepato cytes, whereas no significant response of the enzyme from hepatoma cel ls was evident. Thus, the high CPT-I activity displayed by hepatoma ce lls may be reached by hepatocytes upon challenge to okadaic acid. Reco nstitution experiments with purified mitochondrial and cytoskeletal fr actions showed that the cytoskeleton of hepatocytes produced a more re markable inhibition of CPT-I than the cytoskeleton of Fao cells. The p resent data may be explained by a disruption of interactions between C PT-I and cytoskeletal components in tumor cells that may be involved i n the okadaic acid-induced activation of hepatic CPT-I as previously s uggested. BIOCHEM PHARMACOL 56;11:1485-1488, 1998. (C) 1998 Elsevier S cience Inc.