Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances.
Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances.
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DOI：
10.2174/1874467208666150817111114
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发表时间：
2017
影响因子：
2.7
通讯作者：
Song BJ
中科院分区：
文献类型：
--
作者：
Abdelmegeed MA;Ha SK;Choi Y;Akbar M;Song BJ
酒精性脂肪性肝病(AFLD)和非酒精性脂肪性肝病(NAFLD)是两种在全球范围内蔓延的病理疾病。尽管病因不同，但这两种情况在病理生理机制和进展方面都非常相似。氧化应激通过翻译后蛋白修饰和/或线粒体DNA损伤导致线粒体功能障碍，是AFLD和NAFLD发生发展的主要危险因素。细胞色素P450-2E1是已知的细胞内氧化自由基的重要诱导剂，据报道在AFLD和NAFLD中均显著升高。有趣的是，在内质网(ER)和线粒体中都有表达的CYP2E1亚型，可能导致酒精反应或高脂饮食(HFD)后NAFLD以及肥胖和糖尿病的有害后果。在不同的条件下，内质网和线粒体中的CYP2E1是否同时或顺序地起作用，以及线粒体是否在AFLD和NAFLD的线粒体功能障碍中发挥更明显的作用，目前尚不清楚。本综述的目的是简要描述细胞色素P450-2E_1和由此产生的氧化应激在促进线粒体功能障碍以及AFLD和NAFLD的发生发展中的作用，以阐明线粒体细胞色素P450_2E_1与内质网相关的细胞色素P_2_2_1的功能。最后，我们讨论了与这一领域相关的翻译研究机会。
Alcoholic fatty liver diseases (AFLD) and non-alcoholic fatty liver diseases (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regards to the pathophysiological mechanism and progression despite different causes. Oxidative stress-induced mitochondrial dysfunction through post-translational protein modifications and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes. Whether CYP2E1 in both ER and mitochondria work simultaneously or sequentially in various conditions and whether mitochondrial CYP2E1 may exert more pronounced effects on mitochondrial dysfunction in AFLD and NAFLD are unclear. The aims of this review are to briefly describe the role of CYP2E1 and resultant oxidative stress in promoting mitochondrial dysfunction and the development or progression of AFLD and NAFLD, to shed a light on the function of the mitochondrial CYP2E1 as compared with the ER-associated CYP2E1. We finally discuss translational research opportunities related to this field.