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食蟹猴(猕猴)中CYP2B6 cDNA的鉴定与表征

Identification and characterization of CYP2B6 cDNA in cynomolgus macaques (Macaca fascicularis).

作者信息

Uno Yasuhiro, Matsuno Kiyomi, Nakamura Chika, Utoh Masahiro, Yamazaki Hiroshi

机构信息

Pharmacokinetics and Bioanalysis Center, Kainan, Wakayama 642-0017, Japan.

出版信息

J Vet Med Sci. 2009 Dec;71(12):1653-6. doi: 10.1292/jvms.001653.

Abstract

Cytochrome P450 2B6 (CYP2B6), an important drug-metabolizing enzyme, is involved in the metabolism of prescribed drugs in humans. Despite its importance, cDNA for a CYP2B6 ortholog has not been identified and characterized in cynomolgus macaques, which are frequently used in preclinical studies. In this study, cDNA highly homologous to human CYP2B6 was cloned from the cynomolgus macaque liver. This cDNA contained an open reading frame of 491 amino acids and functional domains characteristic for CYP protein, such as substrate recognition sites and a heme-binding region. Cynomolgus CYP2B6 was expressed predominantly in the liver with some extra-hepatic expression among 10 tissues. Moreover, cynomolgus CYP2B6 revealed activities toward testosterone 16beta-hydroxylation and bupropion hydroxylation. These results suggest that cynomolgus CYP2B6 has a functional role in the liver.

摘要

细胞色素P450 2B6(CYP2B6)是一种重要的药物代谢酶,参与人体处方药的代谢。尽管其很重要,但在常用于临床前研究的食蟹猴中,尚未鉴定和表征CYP2B6直系同源物的cDNA。在本研究中,从食蟹猴肝脏中克隆了与人CYP2B6高度同源的cDNA。该cDNA包含一个491个氨基酸的开放阅读框以及CYP蛋白特有的功能结构域,如底物识别位点和血红素结合区域。食蟹猴CYP2B6主要在肝脏中表达,在10种组织中有一些肝外表达。此外,食蟹猴CYP2B6对睾酮16β-羟基化和安非他酮羟基化具有活性。这些结果表明食蟹猴CYP2B6在肝脏中具有功能作用。

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