Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation

摘要

Reactive oxygen species such as hydrogen peroxide (H_2O_2) are involved in many cellular processes that positively and negatively regulate cell fate. H_2O_2, acting as an intracellular messenger, activates phos-phatidylinositol-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 pro-apoptotic Bcl-2 family member Bax. This phosphorylation suppresses apoptosis and promotes cell survival. Increased survival in the presence of H_2O_2 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 H_2O_2-induced activation of PI3K/Akt influences post-translational modification of Bax and inactivates a key component of the cell death machinery.