萘酚平在成年大鼠原代肝细胞培养物中诱导微粒体细胞色素P452和过氧化物酶体双功能酶mRNA的机制研究。

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

作者信息

Bieri F, Meier V, Stäubli W, Muakkassah-Kelly S F, Waechter F, Sagelsdorff P, Bentley P

机构信息

Central Function Product Safety, Ciba-Geigy Ltd., Basel, Switzerland.

出版信息

Biochem Pharmacol. 1991 Jan 15;41(2):310-2. doi: 10.1016/0006-2952(91)90493-o.

DOI:10.1016/0006-2952(91)90493-o

PMID:1989641

Abstract

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.

摘要

虽然在培养的肝细胞中这两种mRNA的量低于新鲜分离的细胞，但发现加入32微摩尔的萘酚平后它们能被迅速诱导。细胞色素P452 mRNA的诱导总是先于PBE mRNA的诱导，但对于两者来说，最大诱导（比对照高10 - 20倍）在24小时内获得，并且是通过转录激活实现的。在早期时间点（加入萘酚平后1小时和2小时），在没有正在进行的蛋白质合成的情况下，在环己酰亚胺和萘酚平存在时细胞色素P452 mRNA（而非PBE mRNA）的量短暂高于仅存在萘酚平的情况。