Hydrogen peroxide-induced Akt phosphorylation regulates Bax activation.
Authors Sadidi M, Lentz SI, Feldman EL
Submitted By Eva Feldman on 3/24/2010
Status Published
Journal Biochimie
Year 2009
Date Published 5/1/2009
Volume : Pages 91(5) : 577 - 585
PubMed Reference 19278624
Abstract Reactive oxygen species such as hydrogen peroxide (H(2)O(2)) are involved in
many cellular processes that positively and negatively regulate cell fate.
H(2)O(2), 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 pro-apoptotic Bcl-2 family member Bax. This
phosphorylation suppresses apoptosis and promotes cell survival. Increased
survival in the presence of H(2)O(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(2)O(2)-induced activation of PI3K/Akt influences post-translational
modification of Bax and inactivates a key component of the cell death machinery.

Investigators with authorship
Eva FeldmanUniversity of Michigan


Akt1thymoma viral proto-oncogene 1
BaxBcl2-associated X protein
Casp3caspase 3, apoptosis related cysteine protease
Nkx3-1NK-3 transcription factor, locus 1 (Drosophila)
Pik3r1phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)