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Publication

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
Name Institution Eva Feldman University of Michigan

Complications
All Complications Bioinformatics Bone Cardiomyopathy Cardiovascular Gastro-Intestinal (GI) Nephropathy Neuropathy & Neurocognition Pediatric Endocrinology Retinopathy Uropathy Wound Healing

Genes
Symbol Description Akt1 thymoma viral proto-oncogene 1 Bax Bcl2-associated X protein Casp3 caspase 3, apoptosis related cysteine protease Nkx3-1 NK-3 transcription factor, locus 1 (Drosophila) Pik3r1 phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)