Expression, Function and Regulation of Mouse Cytochrome P450 Enzymes: Comparison With Human Cytochrome P450 Enzymes

被引:60
|
作者
Hrycay, E. G. [1 ]
Bandiera, S. M. [1 ]
机构
[1] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada
基金
加拿大健康研究院;
关键词
Cytochrome P450; recombinant CYP enzymes; CYP expression and function; CYP substrates and inhibitors; CYP inducers and suppressors; CYP regulation by receptors; CYP null mice; PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; ARYL-HYDROCARBON RECEPTOR; HUMAN LIVER-MICROSOMES; POLYCYCLIC AROMATIC-HYDROCARBONS; POLYMERASE-CHAIN-REACTION; ACID OMEGA-HYDROXYLASE; IN-SITU HYBRIDIZATION; MESSENGER-RNA LEVELS; CYP1B1 DETERMINES SUSCEPTIBILITY;
D O I
10.2174/138920009790820138
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1151 / 1183
页数:33
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