Iron-induced oxidative injury differentially regulates PI3K/Akt/GSK3beta pathway in synaptic endings from adult and aged rats

URANGA ROMINA; GIUSTO NORMA; SALVADOR GABRIELA AUTOR CORRESP.

TOXICOLOGICAL SCIENCES

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2009 vol. 111 p. 331 - 344

1096-6080

In this work we demonstrate the effect of aging on PI3K/Akt/GSK3â signaling during oxidative injury triggered by free iron, using cerebral cortex synaptic endings isolated from adult (4-month old) and aged (28-month old) rats. Synaptosomes were exposed to FeSO4 (50 µM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3â pathway were evaluated in adult and aged animals. 3-MTT reduction and LDH leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in senile animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3â phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GS3Kâ phosphorylation were dependent on PI3K activation. ERK1/2 activation was temporally coincident with Akt activation and was PI3K-dependent in adults, whereas ERK1/2 activation in senile rats showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to oxidative injury show a differential profile in the activation of PI3K/Akt/GSK3â. These age-related differences in synaptic signaling could be the starting point for further studies aimed at understanding the molecular bases of the aging process.