TanshinoneIIA and Cryptotanshinone Protect against Hypoxia-Induced Mitochondrial Apoptosis in H9c2 Cells

文献类型: 外文期刊

第一作者: Jin, Hyou-Ju

作者: Jin, Hyou-Ju;Ye, Ji-Ming;Li, Chun-Guang;Xie, Xiao-Liang;Li, Chun-Guang

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期刊名称:PLOS ONE ( 影响因子:3.24; 五年影响因子:3.788 )

ISSN: 1932-6203

年卷期: 2013 年 8 卷 1 期

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收录情况: SCI

摘要: Mitochondrial apoptosis pathway is an important target of cardioprotective signalling. Tanshinones, a group of major bioactive compounds isolated from Salvia miltiorrhiza, have been reported with actions against inflammation, oxidative stress, and myocardial ischemia reperfusion injury. However, the actions of these compounds on the chronic hypoxia-related mitochondrial apoptosis pathway have not been investigated. In this study, we examined the effects and molecular mechanisms of two major tanshonones, tanshinone IIA (TIIA) and cryptotanshinone (CT) on hypoxia induced apoptosis in H9c2 cells. Cultured H9c2 cells were treated with TIIA and CT (0.3 and 3 mu M) 2 hr before and during an 8 hr hypoxic period. Chronic hypoxia caused a significant increase in hypoxia inducible factor 1 alpha expression and the cell late apoptosis rate, which was accompanied with an increase in caspase 3 activity, cytochrome c release, mitochondria membrane potential and expression of pro-apoptosis proteins (Bax and Bak). TIIA and CT (0.3 and 3 mu M), in concentrations without affecting the cell viability, significantly inhibited the late apoptosis and the changes of caspase 3 activity, cytochrome c release, and mitochondria membrane potential induced by chronic hypoxia. These compounds also suppressed the overexpression of Bax and reduced the ratio of Bax/Bcl-2. The results indicate that TIIA and CT protect against chronic hypoxia induced cell apoptosis by regulating the mitochondrial apoptosis signaling pathway, involving inhibitions of mitochondria hyperpolarization, cytochrome c release and caspase 3 activity, and balancing anti-and pro-apoptotic proteins in Bcl-2 family proteins.

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