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鼠细胞色素 P450 酶的表达、功能和调控:与人 P450 酶的比较。

Expression, function and regulation of mouse cytochrome P450 enzymes: comparison with human P450 enzymes.

机构信息

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.

出版信息

Curr Drug Metab. 2009 Dec;10(10):1151-83. doi: 10.2174/138920009790820138.

Abstract

The present review focuses on the expression, function and regulation of mouse cytochrome P450 (Cyp) enzymes. Information compiled for mouse Cyp enzymes is compared with data collected for human CYP enzymes. To date, approximately 40 pairs of orthologous mouse-human CYP genes have been identified that encode enzymes performing similar metabolic functions. Recent knowledge concerning the tissue expression of mouse Cyp enzymes from families 1 to 51 is summarized. The catalytic activities of microsomal, mitochondrial and recombinant mouse Cyp enzymes are discussed and their involvement in the metabolism of exogenous and endogenous compounds is highlighted. The role of nuclear receptors, such as the aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor, in regulating the expression of mouse Cyp enzymes is examined. Targeted disruption of selected Cyp genes has generated numerous Cyp null mouse lines used to decipher the role of Cyp enzymes in metabolic, toxicological and biological processes. In conclusion, the laboratory mouse is an indispensable model for exploring human CYP-mediated activities.

摘要

本综述重点介绍了小鼠细胞色素 P450(Cyp)酶的表达、功能和调控。编译的小鼠 Cyp 酶信息与收集的人类 CYP 酶数据进行了比较。迄今为止,已经鉴定出大约 40 对同源的小鼠-人类 CYP 基因,它们编码执行相似代谢功能的酶。本文总结了从小鼠家族 1 到 51 中获得的关于细胞色素 P450 酶的组织表达的最新知识。讨论了微粒体、线粒体和重组小鼠 Cyp 酶的催化活性,并强调了它们在外源和内源性化合物代谢中的作用。研究了核受体(如芳烃受体、组成型雄烷受体和孕烷 X 受体)在调节小鼠 Cyp 酶表达中的作用。通过靶向敲除选定的 Cyp 基因,已经产生了许多 Cyp 基因敲除的小鼠品系,用于解析 Cyp 酶在代谢、毒理学和生物学过程中的作用。总之,实验小鼠是探索人类 CYP 介导的活性不可或缺的模型。

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