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Open Access Highly Accessed Original investigation

Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway

Xuwei Hou*, Zhaohui Hu, Hanying Xu, Jian Xu, Shunrong Zhang, Yigang Zhong, Xiuying He and Ningfu Wang

Author Affiliations

Department of Cardiology, Hangzhou Hospital, Nanjing Medical University & Hangzhou First Municipal Hospital, Hangzhou 310006, China

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Cardiovascular Diabetology 2014, 13:78  doi:10.1186/1475-2840-13-78

Published: 14 April 2014

Abstract

Methods

Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively.

Results

AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes.

Conclusion

This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE.

Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown.

Keywords:
Cardiomyocyte; Autophagy; Advanced glycation end products; Hear function; Signal pathway