Induction of Akt phosphorylation in rat primary astrocytes by H2O2 occurs upstream of phosphatidylinositol 3-kinase: No evidence for oxidative inhibition of PTEN

Citation
S. Salsman et al., Induction of Akt phosphorylation in rat primary astrocytes by H2O2 occurs upstream of phosphatidylinositol 3-kinase: No evidence for oxidative inhibition of PTEN, ARCH BIOCH, 386(2), 2001, pp. 275-280
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
ISSN journal
0003-9861 → ACNP
Volume
386
Issue
2
Year of publication
2001
Pages
275 - 280
Database
ISI
SICI code
0003-9861(20010215)386:2<275:IOAPIR>2.0.ZU;2-1
Abstract
Phosphorylation of the serine/threonine kinase Akt has previously been show n to be increased by treatment of cells with H2O2; the target of H2O2 has n ot been clearly identified. Here we show that treatment of rat primary astr ocytes with H2O2 resulted in increased Akt phosphorylation that was blocked by wortmannin. The thiol-reducing agent N-acetylcysteine had only a slight inhibitory effect. Treatment with rotenone or antimycin A also resulted in increased wortmannin-sensitive Akt phosphorylation, probably by increasing intracellular H2O2 generation by blocking mitochondrial electron transport . Addition of phosphatidylinositol 3,4-bisphosphate to cells also resulted in an increase in Akt phosphorylation. This increase was additive to that i nduced by H2O2 and was also blocked by wortmannin. These results suggest th at activation of Akt by H2O2 occurs upstream of phosphatidylinositol 3-kina se (PI 3-K) activity in astrocytes. The data indicate that major oxidative effects do not occur at the level of the PI 3-K-antagonizing phosphatase PT EN. (C) 2001 Academic Press.