Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
Cell Stress Chaperones. 2011 Mar;16(2):143-52. doi: 10.1007/s12192-010-0226-6. Epub 2010 Oct 3.
We have previously shown that heat shock protein 70 (HSP70) markedly inhibits H(2)O(2)-induced apoptosis in mouse C2C12 myogenic cells by reducing the release of Smac. However, the molecular mechanism by which HSP70 interferes with Smac release during oxidative stress-induced apoptosis is not understood. In the current study, we showed that HSP70 increased the stability of Bcl-2 during oxidative stress. An antisense phosphorothioate oligonucleotide against Bcl-2 caused selective inhibition of Bcl-2 protein expression induced by HSP70 and significantly attenuated HSP70-mediated cell protection against H(2)O(2)-induced release of Smac and apoptosis. Taken together, our results indicate that there are important relationships among HSP70, Bcl-2, release of Smac, and induction of apoptosis by oxidative stress.
我们之前已经表明，热休克蛋白 70（HSP70）通过减少 Smac 的释放，显著抑制 H(2)O(2)-诱导的小鼠 C2C12 成肌细胞凋亡。然而，HSP70 在氧化应激诱导的细胞凋亡过程中干扰 Smac 释放的分子机制尚不清楚。在本研究中，我们表明 HSP70 在氧化应激过程中增加了 Bcl-2 的稳定性。针对 Bcl-2 的反义硫代磷酸寡核苷酸选择性地抑制了 HSP70 诱导的 Bcl-2 蛋白表达，并显著减弱了 HSP70 介导的对 H(2)O(2)-诱导的 Smac 释放和凋亡的细胞保护作用。总之，我们的结果表明，HSP70、Bcl-2、Smac 的释放和氧化应激诱导的凋亡之间存在重要关系。
