Studies on the mechanism of induction of microsomal cytochrome P452 and peroxisomal bifunctional enzyme mRNAs by nafenopin in primary cultures of adult rat hepatocytes

• Published in: Biochemical pharmacology Vol. 41; no. 2; p. 310
• Main Authors: Bieri, F, Meier, V, Stäubli, W, Muakkassah-Kelly, S F, Waechter, F, Sagelsdorff, P, Bentley, P
• Format: Journal Article
• Language: English
• Published: England 15.01.1991
• Subjects: 3-Hydroxyacyl CoA Dehydrogenases - biosynthesis; 3-Hydroxyacyl CoA Dehydrogenases - genetics; Animals; Cells, Cultured - drug effects; Cycloheximide - pharmacology; Cytochromes - biosynthesis; Cytochromes - genetics; Enoyl-CoA Hydratase - biosynthesis; Enoyl-CoA Hydratase - genetics; Enzyme Induction; Isomerases; Microbodies - enzymology; Microsomes, Liver - enzymology; Multienzyme Complexes - biosynthesis; Multienzyme Complexes - genetics; Nafenopin - pharmacology; Peroxisomal Bifunctional Enzyme; Rats; RNA, Messenger - biosynthesis; Time Factors
• ISSN: 0006-2952
• DOI: 10.1016/0006-2952(91)90493-O

The amount of the two mRNAs although lower in cultured hepatocytes than in freshly isolated cells was found to be rapidly inducible upon the addition of 32 microM nafenopin. The induction of cyt.P452 mRNA always preceded the induction of PBE mRNA, but for both, the maximal induction (10-20-fold over control) was obtained within 24 hr and was achieved by transcriptional activation. At early time points (1 and 2 hr after the addition of nafenopin), in the absence of on-going protein synthesis, the amount of cyt.P452 mRNA (and not of PBE mRNA) was transiently higher in the presence of cycloheximide and nafenopin than in the presence of nafenopin alone.