Effect of nicardipine, a calcium antagonist, on induction of peroxisomal enzymes by dehydroepiandrosterone sulfate in cultured rat hepatocytes.
We examined the effect of nicardipine, a calcium antagonist, on the induction of peroxisomal enzymes, such as acyl-CoA oxidase and carnitine acetyltransferase, by dehydroepiandrosterone sulfate (DHEAS) and clofibric acid (CPIB), in primary cultured rat hepatocytes. Peroxisomal beta-oxidation and carnitine acetyltransferase activities were increased 11- and 20-fold, respectively, after 5 days of treatment with DHEAS (40 microM). However, 60 microM nicardipine significantly suppressed the induction of both of these activities by DHEAS to about 2-fold that of the control. This suppression was found to be both dose- and time-dependent. Immunoblot and Northern blot analyses of acyl-CoA oxidase revealed that suppression by nicardipine of the induction of peroxisomal beta-oxidation activity would be responsible for an increase in the amount of mRNA. In addition, the manner in which nicardipine suppressed the induction of peroxisomal beta-oxidation and carnitine acetyltransferase activity, was similar to that of clofibric acid. These findings suggest that in the calcium-dependent pathway, the mechanism for the induction of peroxisomal enzymes by DHEAS is basically the same as that by clofibric acid, a typical peroxisome proliferator. The present results also support our previous hypothesis that calcium may play an important role in the induction of these enzymes by peroxisome proliferators.
Zhang
H
H
Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Tamura
H
H
Yamada
J
J
Watanabe
T
T
Suga
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002995:Clofibric Acid / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002995:Clofibric Acid; D019314:Dehydroepiandrosterone Sulfate; D009529:Nicardipine