Increased stability of Bcl-2 in HSP70-mediated protection against apoptosis induced by oxidative stress.
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.
Jiang
Bimei
B
Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
Liang
Pengfei
P
Deng
Gonghua
G
Tu
Zizhi
Z
Liu
Meidong
M
Xiao
Xianzhong
X
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018384:Oxidative Stress; D055550:Protein Stability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014162:Transfection
D018840:HSP70 Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases