Expression and induction of CYP3As in human fetal hepatocytes
Expression and induction of CYP3As in human fetal hepatocytes
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DOI：
10.1016/j.bbrc.2004.04.041
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发表时间：
2004-05-28
影响因子：
3.1
通讯作者：
Ohmori, S
中科院分区：
文献类型：
--
作者：
Matsunaga, T;Maruyama, M;Ohmori, S
地塞米松(DEX)可显著上调细胞色素P3A4和细胞色素P3A7mRNA的表达，而利福平(RIF)对其无明显影响。地塞米松、RIF和苯巴比妥对细胞色素P3A5基因表达水平无明显影响。DEX诱导的睾酮6β-羟基酶活性约为对照的2倍。然而，联合应用RIF并不改变地塞米松诱导的细胞色素P3A基因表达和睾酮6β-羟基酶活性。糖皮质激素受体(GR)拮抗剂RU486呈剂量依赖性抑制Dex诱导的细胞色素P3A基因表达。在5µM RU486处，地塞米松诱导的细胞色素P3A4、细胞色素P3A5和细胞色素P3A7的表达几乎完全被抑制。这些结果表明，在人胎肝细胞中，PXR不参与地塞米松诱导的细胞色素P3A4和细胞色素P3A7的诱导，这种诱导是由GR直接介导的。(C)2004 Elsevier Inc.保留所有权利。
CYP3A4 and CYP3A7 mRNA expression levels were markedly up-regulated by dexamethasone (DEX), but not by rifampicin (RIF). CYP3A5 mRNA level was not increased significantly by DEX, RIF, or phenobarbital. Testosterone 6 6beta-hydroxylase activity was induced to about 2-fold of control by DEX. However, concomitant treatment with RIF did not alter DEX-mediated induction of CYP3A mRNA expression and testosterone 6beta-hydroxylase activity. DEX-mediated induction of CYP3A mRNA was suppressed in a dose-dependent manner by RU486, a glucocorticoid receptor (GR) antagonist. At 5muM RU486, DEX-mediated induction of CYP3A4, CYP3A5, and CYP3A7 mRNA expression was inhibited almost completely. These results suggest that, in human fetal hepatocytes, PXR is not involved in DEX-mediated induction of CYP3A4 and CYP3A7, and that the induction is mediated directly by GR. (C) 2004 Elsevier Inc. All rights reserved.