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Activation of phosphoinositide‐3 kinase/Akt pathway by FeSO 4 in rat cerebral cortex synaptic endings
Author(s) -
Uranga Romina M.,
Mateos Melina V.,
Giusto Norma M.,
Salvador Gabriela A.
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21406
Subject(s) - neuroscience , chemistry , cerebral cortex , protein kinase b , microbiology and biotechnology , biology , signal transduction
Abstract The aim of this work was to study the involvement of the phosphoinositide‐3‐kinase (PI3K)/Akt pathway in synaptic endings incubated under oxidative stress conditions. Synaptosomes purified from rat cerebral cortex were exposed to FeSO 4 (50 μM) for different periods of time. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenate (LDH) leakage were significantly affected after 5 min of incubation in the presence of FeSO 4 , with respect to control conditions. In whole synaptosomes incubated in the presence of [γ‐ 32 P]ATP, phosphoinositide (PPI) labeling was increased after 5 min of Fe 2+ exposure. This effect was prevented by the specific PI3K inhibitor LY294002. Anti‐p85 immunoprecipitates (IPs) obtained from synaptosomes preincubated with Fe 2+ (5 min) showed a PI3K activity two‐fold higher than the activity recovered under control conditions. Additionally, Akt activation was temporally coincident with PI3K activation. LY294002 was not able to prevent the LDH leakage and diminution of MTT reduction induced by Fe 2+ . Our results demonstrate that free iron provokes the early activation of PI3K/Akt pathway, but this activation is not sufficient for protecting synaptic endings from oxidative damage. © 2007 Wiley‐Liss, Inc.