Free iron stimulates PI3K/Akt pathway in rat cerebral cortex synaptic endings

URANGA, ROMINA; MATEOS, MELINA; GIUSTO, NORMA; SALVADOR, GABRIELA

Rosario, Santa Fe, Argentina.

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

The presence of phosphoinositide-3-kinase (PI3K)/Akt pathway in cerebral cortex synaptic endings (syn) has been previously described. The goal of this work was to determine the involvement of PI3K in oxidative damage triggered by free iron. Purified syn were exposed to FeSO4 (50 µM) for different periods of time. Fe2+ effects on synaptosomes were evaluated by measuring lactate dehydrogenase (LDH) leakage, protein tyrosine phosphorylation and mitochondrial integrity by MTT assay. The most striking effects on glutamate uptake, LDH release and tyrosine phosphorylation were observed after 1 h of incubation with the metal ion. For determining PI3K activity, synaptosomes preincubated with Fe2+ for 5 min were immunoprecipitated with anti-p85 antibody. PI3K activity from synaptosomes incubated with Fe2+ was 2-fold higher than the activity found under control condition. Akt activation was only evidenced after 5 min of incubation in the presence of Fe2+. Our results demonstrate an early activation of PI3K/Akt pathway in cerebral cortex synaptic endings even though the most deleterious effects of oxidative stress were evidenced at longer times of incubation (30 and 60 min).