Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats

Brahma-related gene 1 (Brg1) is a key gene in inducing the expression of important endogenous antioxidant enzymes, including heme oxygenase-1 (HO-1) which is central to cardioprotection, while cardiac HO-1 expression is reduced in diabetes. It is unknown whether or not cardiac Brg1 expression is red...

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Main Authors: Jinjin Xu, Shaoqing Lei, Yanan Liu, Xia Gao, Michael G. Irwin, Zhong-yuan Xia, Ziqing Hei, Xiaoliang Gan, Tingting Wang, Zhengyuan Xia
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2013/716219
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author Jinjin Xu
Shaoqing Lei
Yanan Liu
Xia Gao
Michael G. Irwin
Zhong-yuan Xia
Ziqing Hei
Xiaoliang Gan
Tingting Wang
Zhengyuan Xia
author_facet Jinjin Xu
Shaoqing Lei
Yanan Liu
Xia Gao
Michael G. Irwin
Zhong-yuan Xia
Ziqing Hei
Xiaoliang Gan
Tingting Wang
Zhengyuan Xia
author_sort Jinjin Xu
collection DOAJ
description Brahma-related gene 1 (Brg1) is a key gene in inducing the expression of important endogenous antioxidant enzymes, including heme oxygenase-1 (HO-1) which is central to cardioprotection, while cardiac HO-1 expression is reduced in diabetes. It is unknown whether or not cardiac Brg1 expression is reduced in diabetes. We hypothesize that cardiac Brg1 expression is reduced in diabetes which can be restored by antioxidant treatment with N-acetylcysteine (NAC). Control (C) and streptozotocin-induced diabetic (D) rats were treated with NAC in drinking water or placebo for 4 weeks. Plasma and cardiac free15-F2t-isoprostane in diabetic rats were increased, accompanied with increased plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), while cardiac Brg1, p-STAT3 and HO-1 protein expression levels were significantly decreased. Left ventricle weight/body weight ratio was higher, while the peak velocities of early (E) and late (A) flow ratio was lower in diabetic than in C rats. NAC normalized tissue and plasma levels of 15-F2t-isoprostane, significantly increased cardiac Brg1, HO-1 and p-STAT3 protein expression levels and reduced TNF-alpha and IL-6, resulting in improved cardiac function. In conclusion, myocardial Brg1 is reduced in diabetes and enhancement of cardiac Brg1 expression may represent a novel mechanism whereby NAC confers cardioprotection.
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series Journal of Diabetes Research
spelling doaj-art-ae8804e2e32d4fa68cd76dcd9d7448ac2025-08-20T02:23:08ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/716219716219Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic RatsJinjin Xu0Shaoqing Lei1Yanan Liu2Xia Gao3Michael G. Irwin4Zhong-yuan Xia5Ziqing Hei6Xiaoliang Gan7Tingting Wang8Zhengyuan Xia9Department of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Anesthesiology, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, ChinaDepartment of Anesthesiology, 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, ChinaDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongDepartment of Anaesthesiology, The University of Hong Kong, HKSAR, Hong KongBrahma-related gene 1 (Brg1) is a key gene in inducing the expression of important endogenous antioxidant enzymes, including heme oxygenase-1 (HO-1) which is central to cardioprotection, while cardiac HO-1 expression is reduced in diabetes. It is unknown whether or not cardiac Brg1 expression is reduced in diabetes. We hypothesize that cardiac Brg1 expression is reduced in diabetes which can be restored by antioxidant treatment with N-acetylcysteine (NAC). Control (C) and streptozotocin-induced diabetic (D) rats were treated with NAC in drinking water or placebo for 4 weeks. Plasma and cardiac free15-F2t-isoprostane in diabetic rats were increased, accompanied with increased plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), while cardiac Brg1, p-STAT3 and HO-1 protein expression levels were significantly decreased. Left ventricle weight/body weight ratio was higher, while the peak velocities of early (E) and late (A) flow ratio was lower in diabetic than in C rats. NAC normalized tissue and plasma levels of 15-F2t-isoprostane, significantly increased cardiac Brg1, HO-1 and p-STAT3 protein expression levels and reduced TNF-alpha and IL-6, resulting in improved cardiac function. In conclusion, myocardial Brg1 is reduced in diabetes and enhancement of cardiac Brg1 expression may represent a novel mechanism whereby NAC confers cardioprotection.http://dx.doi.org/10.1155/2013/716219
spellingShingle Jinjin Xu
Shaoqing Lei
Yanan Liu
Xia Gao
Michael G. Irwin
Zhong-yuan Xia
Ziqing Hei
Xiaoliang Gan
Tingting Wang
Zhengyuan Xia
Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
Journal of Diabetes Research
title Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
title_full Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
title_fullStr Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
title_full_unstemmed Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
title_short Antioxidant N-Acetylcysteine Attenuates the Reduction of Brg1 Protein Expression in the Myocardium of Type 1 Diabetic Rats
title_sort antioxidant n acetylcysteine attenuates the reduction of brg1 protein expression in the myocardium of type 1 diabetic rats
url http://dx.doi.org/10.1155/2013/716219
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