期刊
BIOCHIMIE
卷 91, 期 5, 页码 577-585出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2009.01.010
关键词
Reactive oxygen species (ROS); PI3K/Akt; Bax; Mitochondria; Apoptosis
资金
- National Institutes of Health [NS36778, NS38849, DK 076160]
- Diabetes Research Foundation Center for the Study of Complications in Diabetes
- Program for Neurology Research Discovery
- A. Alfred Taubman Medical Research Institute at the University of Michigan
- National Institute of Diabetes & Digestive & Kidney Diseases [NIH5P60 DK20572]
- UM-BRCF
Reactive oxygen species such as hydrogen peroxide (H2O2) are involved in many cellular processes that positively and negatively regulate cell fate. H2O2, acting as an intracellular messenger, activates phosphatidylinositol-3 kinase (PI3K) and its downstream target Akt, and promotes cell survival. The aim of the current study was to understand the mechanism by which PI3K/Akt signaling promotes survival in SH-SY5Y neuroblastoma cells. We demonstrate that PI3K/Akt mediates phosphorylation of the proapoptotic Bcl-2 family member Bax. This phosphorylation suppresses apoptosis and promotes cell survival. Increased survival in the presence of H2O2 was blocked by LY294002, an inhibitor of PI3K activation. LY294002 prevented Bax phosphorylation and resulted in Bax translocation to the mitochondria, cytochrome c release, caspase-3 activation, and cell death. Collectively, these findings reveal a mechanism by which H2O2-induced activation of PI3K/Akt influences post-translational modification of Bax and inactivates a key component of the cell death machinery. (C) 2009 Elsevier Masson SAS. All rights reserved.
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