mTORC2型
蛋白激酶B
PI3K/AKT/mTOR通路
细胞凋亡
孵化
内科学
内分泌学
生物
下调和上调
mTORC1型
医学
生物化学
基因
作者
Xiong Guo,Chong Huang,Kun Lian,Shan Wang,Haikang Zhao,Feng Yan,Xiaomeng Zhang,Jinglong Zhang,Huaning Xie,Rui An,Ling Tao
标识
DOI:10.1016/j.bbrc.2016.09.162
摘要
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.
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