alexa Role of Nuclear Factor Erythroid 2-Like 2 in the Induction of Cytochrome P450 2a5 in Vivo of Nonalcoholic Fatty Liver Disease | OMICS International | Abstract
ISSN: 2155-6156

Journal of Diabetes & Metabolism
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Research Article

Role of Nuclear Factor Erythroid 2-Like 2 in the Induction of Cytochrome P450 2a5 in Vivo of Nonalcoholic Fatty Liver Disease

Yizhe Cui1,2, Qiuju Wang2, Chunhua Wang1, Xing Yi1, Yue Qi1, Guangliang Li1 and Xiuying Zhang1*

1College of Veterinary Medicine, Northeast Agricultural University, Mucai Street, Xiangfang District, Harbin 150030, Heilongjiang, China

2College of Animal Sciences and Technology, Heilongjiang Bayi Agricultural University, Xinyang Road, New Development District, Daqing 163319, Heilongjiang, China

*Corresponding Author:
Xiuying Zhang
Department of Basic Veterinary Science
College of Veterinary Medicine, Northeast Agriculture University
Mucai Street, Xiangfang District, Harbin150030, Heilongjiang, China
Tel/Fax: +86 451 55190674
E-mail: [email protected]

Received date: April 23, 2014; Accepted date: January 02, 2015; Published date: January 04, 2015

Citation: Cui Y, Wang Q, Wang C, Yi X, Qi Y, et al. (2015) Role of Nuclear Factor Erythroid 2-Like 2 in the Induction of Cytochrome P450 2a5 in Vivo of Nonalcoholic Fatty Liver Disease. J Diabetes Metab 6:488. doi: 10.4172/2155-6156.1000488

Copyright: © 2015 Cui Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mouse cytochrome P450 2A5 (Cyp2a5) is upregulated in various pathophysiological liver disease and induced by structurally variable hepatotoxic chemicals. A putative common feature for all of these conditions is altered cellular redox status. Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor that is post-translationally regulated by oxidative stress and controls the transcription of numerous protective target genes. In order to determine if upregulation of Cyp2a5 by Nonalcoholic fatty liver disease (NAFLD) was mediated through Nrf2, we applied Nrf2 knockout mice (Nrf2-/-) to examine the Cyp2a5 mRNA and protein levels compared to wild type mice. Furthermore, the interaction of Nrf2 with Cyp2a5 was confirmed by co-immunoprecipitation (co-IP) in vivo. The NAFLD increased the Nrf2 mRNA and protein levels in wild type mice and also increased the Cyp2a5 mRNA and protein levels resulted from translocation of Nrf2 into the nucleus. However, the expression and activity of Cyp2a5 were no difference in the Nrf2 knockout mice. Nuclear immunohistochemical staining of Nrf2, an indicator of activation of the transcription factor, was evident in NAFLD. Co-IP experiments showed that Nrf2 binds to the Cyp2a5. Our current results unequivocally show that expression of Cyp2a5 is tightly controlled by Nrf2 in liver. Nrf2 is needed for constitutive expression of Cyp2a5, and Cyp2a5 is also sensitively upregulated by an increased level of Nrf2 protein. Therefore, Cyp2a5 upregulation could be a useful indicator for hepatic activation of the Nrf2 pathway.

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