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The nuclear receptor CAR modulates alcohol-induced liver injury

被引：27
作者：
Chen, Xiaosong [2 ]
Meng, Zhipeng [3 ]
Wang, Xiaoqiong [5 ]
Zeng, Samuel [4 ]
Huang, Wendong [1 ,3 ]
机构：
[1] City Hope Natl Med Ctr, Div Gene Regulat & Drug Discovery, Beckman Res Inst, Duarte, CA 91010 USA
[2] Fujian Med Univ, Dept Plast Surg, Union Hosp, Fuzhou, Fujian, Peoples R China
[3] City Hope Natl Med Ctr, Irell & Manella Grad Sch Biol Sci, Duarte, CA 91010 USA
[4] City Hope Natl Med Ctr, Eugene & Ruth Roberts Summer Student Program, Beckman Res Inst, Duarte, CA 91010 USA
[5] Zhejiang Univ, Sch Med, Dept Pathol, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China
来源：
LABORATORY INVESTIGATION | 2011年 / 91卷 / 08期
关键词：
alcohol; alcohol dehydrogenase; aldehyde dehydrogenase; constitutive androstane receptor; liver injury; DRUG-METABOLISM; FATTY LIVER; INDUCTION; ACTIVATION;
D O I：
10.1038/labinvest.2011.68
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
100103 [病原生物学]; 100218 [急诊医学];
摘要：
The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and a sensor and detoxifier of both xenobiotics and endobiotics. Recent studies also show that CAR participates in metabolism of glucose and lipid, and has an important role in fatty liver disease and diabetes. In this study, we investigate the roles of CAR in chronic and acute alcohol-induced liver injuries. The results showed that absence of CAR in rodents led to significantly increased susceptibility to chronic alcohol-induced liver injury, which was accompanied with elevated hepatocyte apoptosis and fat accumulation. However, pre-activation of CAR by a CAR agonist, TCPOBOP, strongly enhanced the hepatic toxicity by both chronic and acute alcohol infusion in wild-type, but not in CAR(-/-) mice. Gene expression analyses indicated that CAR pre-activation and alcohol infusion synergistically decreased the expression of enzymes that metabolize the alcohol in liver. These results support a role of CAR in modulating alcoholic liver injury and imply a risk of synergistic liver toxicity induced by alcohol and CAR activation. Laboratory Investigation (2011) 91, 1136-1145; doi:10.1038/labinvest.2011.68; published online 25 April 2011
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收藏
页码：1136 / 1145
页数：10
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