Transcriptional Induction of Acyl-CoA Oxidase by Dehydroepiandrosterone Sulfate in Cultured Rat Hepatocytes

抄録

To elucidate the molecular basis of the induction of peroxisomal enzymes, transcriptional regulation of the acyl-CoA oxidase (AOX) gane by dehydroepiandrosterone sulfate (DHEAS) was examined using primary cultures of rat hepatocytes. Incubation of the hepatocytes with 0.1 mM DHEAS resulted in a progressive increase in the cellular AOX mRNA level, which after 24 h reached a 5.6-fold higher level than that in the control cells treated with vehicle alone. However, this mRNA induction was completely inhibited by α-amanitin, an RNA polymerase II inhibitor. When examined by the nuclear run-on transcription assay, the rate of de novo synthesis of AOX mRNA was 3- to 4-fold higher in the hepatocytes exposed to DHEAS than in the control cells, even after 3 h. These results indicate that DHEAS acts directly on hepatocytes to activate the transcription of the AOX gene, which leads to the marked induction of AOX in the cell.