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Int. J. Mol. Sci. 2013, 14(2), 2242-2257;

Advanced Glycation End Product (AGE)-AGE Receptor (RAGE) System Upregulated Connexin43 Expression in Rat Cardiomyocytes via PKC and Erk MAPK Pathways

Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
Author to whom correspondence should be addressed.
Received: 21 August 2012 / Revised: 19 December 2012 / Accepted: 8 January 2013 / Published: 24 January 2013
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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The remodeling of cardiac gap junction contributes to the arrhythmias in a diabetic heart. We previously reported that high glucose reduced Cx43 protein level in neonatal rat cardiomyocytes. But, the effect and mechanisms of advanced glycation end product (AGE) on Cx43 expression still remain unclear. In this study, we measured the AGE receptor (RAGE) and Cx43 expression by immunohistochemisty in AGE-infused Sprague-Dawley (SD) rats. In vitro, the Cx43 and RAGE levels were detected in AGE-treated cardiomyocytes by Western blot and real-time RT-PCR. The function of cells coupling was measured by Scrap loading dye transfer assay. Our results showed that the AGE-infused rat hearts exhibited increased cardiac RAGE and Cx43, as well as Cx43 redistribution. In cultured cardiomyocytes, AGE elevated RAGE expression in a time- and dose-dependent manner. Cx43 protein and mRNA levels were upregulated by AGE (200 mg/L, 24 h), but the gap junction function was not enhanced. RAGE-targeted knock-down or the addition of PKC, and Erk inhibitors abolished the effect of AGE on Cx43. Therefore, AGE-RAGE system might elevate Cx43 expression in rat cardiomyocytes by activating PKC and Erk MAPK pathways, and it also enhanced Cx43 redistribution in vivo, which might contribute to the arrhythmias in diabetes. View Full-Text
Keywords: advanced glycation end product; connexin43; cardiomyocytes; diabetes advanced glycation end product; connexin43; cardiomyocytes; diabetes
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Yu, L.; Zhao, Y.; Xu, S.; Ding, F.; Jin, C.; Fu, G.; Weng, S. Advanced Glycation End Product (AGE)-AGE Receptor (RAGE) System Upregulated Connexin43 Expression in Rat Cardiomyocytes via PKC and Erk MAPK Pathways. Int. J. Mol. Sci. 2013, 14, 2242-2257.

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