tailieunhanh - Báo cáo khoa học: Expression of CYP2E1 increases oxidative stress and induces apoptosis of cardiomyocytes in transgenic mice

Cytochrome P450 2E1 (CYP2E1) is an effective generator of reactive oxy-gen species. Marked expression of CYP2E1 occurs in the heart and it is known to be regulated in the course of progression of myocardial ischemia and cardiomyopathy. | IFEBS Journal Expression of CYP2E1 increases oxidative stress and induces apoptosis of cardiomyocytes in transgenic mice Wei Zhang1 Dan Lu1 Wei Dong1 Li Zhang1 Xiaojuan Zhang1 Xiongzhi Quan1 Chunmei Ma2 Hong Lian1 and Lianfeng Zhang1 2 1 Key Laboratory of Human Disease Comparative Medicine Ministry of Health Institute of Laboratory AnimalScience Chinese Academy of MedicalSciences Comparative MedicalCenter Peking Union MedicalCollege Beijing China 2 Key Laboratory of Human Diseases Animal Model State Administration of TraditionalChinese Medicine Institute of Laboratory Animal Science Chinese Academy of MedicalSciences Comparative MedicalCenter Peking Union MedicalCollege Beijing China Keywords apoptosis CYP2E1 dilated cardiomyopathy oxidative stress transgenic mice Correspondence L. Zhang Building 5 Panjiayuan Nanli Chaoyang District Beijing 100021 China Fax 86 010 67710812 Tel 86 010 87778442 E-mail zhanglf@ Received 14 November 2010 revised 11 February 2011 accepted 21 February 2011 doi Cytochrome P450 2E1 CYP2E1 is an effective generator of reactive oxygen species. Marked expression of CYP2E1 occurs in the heart and it is known to be regulated in the course of progression of myocardial ischemia and cardiomyopathy. We provide evidence that the expression of CYP2E1 is strongly up-regulated in cTnTR141W transgenic mice with dilated cardiomyopathy. Heart tissue-specific CYP2E1 transgenic mice were produced to study the effects of CYP2E1 overexpression on the heart. Increased mortality chamber dilation and contractile dysfunction as well as myocyte disarray interstitial fibrosis ultrastructural degeneration with myofibrillar disorganization and mitochondria damage were observed in CYP2E1 transgenic mice and cTnTR141W transgenic mice. In addition levels of H2O2 and malondialdehyde were increased and levels of glutathione and total antioxidant capability were strongly reduced in CYP2E1 transgenic mice and cTnTR141W transgenic .