Bani M H, Tohkin M, Ushio F, Fukuhara M
Department of Pharmaceutical Sciences, National Institute of Public Health, Tokyo, 108, Japan.
Arch Biochem Biophys. 1998 Aug 15;356(2):100-6. doi: 10.1006/abbi.1998.0754.
Recently, we isolated a novel Syrian hamster cDNA clone that encodes a protein which has been named CYP3A31. In primary hepatocyte cultures, CYP3A31 is dramatically induced by phenobarbital. To elucidate the mechanism of this induction, we first studied the effects of cAMP on phenobarbital-induced CYP3A31 expression using forskolin and N6,O2'-dibutyryl cAMP in hepatocyte cultures. At 100 microM, forskolin significantly inhibited both the phenobarbital-induced CYP3A31 mRNAs expression and the testosterone 6beta-hydroxylation activity related to the CYP3A subfamily in rats, whereas 0.1 microM forskolin potentiated the phenobarbital induction of CYP3A31 mRNA and the testosterone 6beta-hydroxylation activity. Treatment with N6,O2'-dibutyryl cAMP resulted in an inhibition of phenobarbital-induced CYP3A31 gene expression and testosterone 6beta-hydroxylation activity. Increasing amounts of transfected cAMP-response element binding proteins (CREB) or CREB-binding proteins in hamster hepatocytes reduced the phenobarbital-induction of CYP3A31 mRNAs expression. These results suggest that in vitro induction of CYP3A31 by phenobarbital in Syrian hamster hepatocytes is regulated by a cAMP-dependent pathway.
最近，我们分离出了一个新的叙利亚仓鼠cDNA克隆，它编码一种名为CYP3A31的蛋白质。在原代肝细胞培养中，苯巴比妥可显著诱导CYP3A31的表达。为了阐明这种诱导的机制，我们首先在肝细胞培养中使用福斯可林和N6,O2'-二丁酰环磷腺苷研究了环磷腺苷（cAMP）对苯巴比妥诱导的CYP3A31表达的影响。在100微摩尔浓度下，福斯可林显著抑制了苯巴比妥诱导的CYP3A31 mRNA表达以及与大鼠CYP3A亚家族相关的睾酮6β-羟化活性，而0.1微摩尔浓度的福斯可林则增强了苯巴比妥对CYP3A31 mRNA的诱导作用以及睾酮6β-羟化活性。用N6,O2'-二丁酰环磷腺苷处理导致苯巴比妥诱导的CYP3A31基因表达和睾酮6β-羟化活性受到抑制。仓鼠肝细胞中转染的环磷腺苷反应元件结合蛋白（CREB）或CREB结合蛋白数量增加，会降低苯巴比妥对CYP3A31 mRNA表达的诱导作用。这些结果表明，叙利亚仓鼠肝细胞中苯巴比妥对CYP3A31的体外诱导受cAMP依赖性途径调控。
