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BCKA down-regulates mTORC2-Akt signal and enhances apoptosis susceptibility in cardiomyocytes

Xiong Guo¹, Chong Huang¹, Kun Lian¹

¹Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

Biochemical and Biophysical Research Communications

|October 5, 2016

Abstract:

Diabetic mellitus (DM) portends poor prognosis concerning pressure overloaded heart disease. Branched-chain amino acids (BCAAs), elements of essential amino acids, have been found altered in its catabolism in diabetes decades ago. However, the relationship between BCAAs and DM induced deterioration of pressure overloaded heart disease remains controversial. This study is aimed to investigate the particular effect of BCKA, a metabolite of BCAA, on myocardial injury induced by pressure overloaded. Primary cardiomyocytes were incubated with or without BCKA and followed by treatment with isoproterenol (ISO); then cell viability was detected by CCK8 and apoptosis was examined by TUNNEL stain and caspase-3 activity analysis. Compared to non-BCKA incubated group, BCKA incubation decreased cell survival and increased apoptosis concentration dependently. Furthermore, Western blot assay showed that mTORC2-Akt pathway was significantly inactivated by BCKA incubation. Moreover, overexpression of rictor, a vital component of mTORC2, significantly abolished the adverse effects of BCKA on apoptosis susceptibility of cardiomyocytes. These results indicate that BCKA contribute to vulnerability of cardiomyocytes in stimulated stress via inactivation of mTORC2-Akt pathway.

Keywords:

Akt Apoptosis BCKA Diabetes Isoproterenol mTORC2

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