Induction of Cytochrome P450 2A6 by Bilirubin in Human Hepatocytes

• 作者: Hiromi Tanii Hiroshi Iwata Mikako Torii Shuichi Sekine Toshiharu Horie Yoshihisa Shitara
• 来源期刊: 药理与制药(英文)
• 学科: 医学
• 关键词: CYP2A6 HEPATOCYTES HYPERBILIRUBINEMIA RT-PCR
• 年，卷（期）: 2013,（2）
• 页码范围: 182-190
• 页数: 9页
• 分类号: R73

摘要

The influence of bilirubin on mRNA expression of cytochrome P450 (CYP), UDP-glucuronosyltransferase (UGT) and nuclear receptors in human hepatocytes was investigated. The treatment of the hepatocytes with 40 μg/mL bilirubin, which corresponds to hyperbilirubinemia, resulted in 1.7-fold increase of CYP2A6 mRNA compared to the vehicle control while CYP2A6 mRNA did not change after treatment with 1 μg/mL bilirubin, corresponding to physiologically normal level. No significant change of mRNA expression by 40 μg/mL bilirubin treatment was observed for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, UGT1A1, UGT1A3, UGT1A6, UGT2B4, UGT2B7, UGT2B10 and UGT2B15, constitutive androstane receptor (CAR), pregnane X receptor (PXR), retinoid X receptor α (RXRα) and hepatocyte nuclear factor-4α (HNF-4α). The induction profile of bilirubin was different from that of rifampicin, a typical PXR activator. This study demonstrated that CYP2A6 can be induced by bilirubin in a concentration dependent manner.