Int. J. Mol. Sci. 2013, 14(2), 2242-2257; doi:10.3390/ijms14022242
Article

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

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Received: 21 August 2012; in revised form: 19 December 2012 / Accepted: 8 January 2013 / Published: 24 January 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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.
Keywords: advanced glycation end product; connexin43; cardiomyocytes; diabetes
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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2013; 14(2):2242-2257.

Chicago/Turabian Style

Yu, Lu; Zhao, Yanbo; Xu, Shengjie; Ding, Fang; Jin, Chongying; Fu, Guosheng; Weng, Shaoxiang. 2013. "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. 14, no. 2: 2242-2257.

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