Oxidative Stress triggers phosphoinositide 3-kinase/Akt, c-Src and Erk signaling in rat cerebral cortex synaptic endings¡±

URANGA, ROMINA; GIUSTO, NORMA; SALVADOR GABRIELA

Washington DC, Estados Unidos

Congreso; 38th Annual Meeting of the Society for Neuroscience (SFN), 15 al 19 de noviembre de 2008, Washington DC, Estados Unidos; 2008

Society For Neuroscience

¡°Oxidative Stress triggers phosphoinositide- 3-kinase/Akt, cSrc and Erk signaling rat cerebral cortex synaptic endings¡±. Uranga, R.M. 1, 2, 3, Giusto, N.M. 1, 2, 3, Salvador, G.A. 1, 2, 31 Instituto de Investigaciones Bioqu¨ªmicas de Bah¨ªa Blanca, Bah¨ªa Blanca, Argentina.2 Universidad Nacional del Sur, Bah¨ªa Blanca, Argentina.3 Consejo Nacional de Investigaciones Cient¨ªficas y T¨¦cnicas, Bah¨ªa Blanca, Argentina.Neuron exposure to metal ions such as Fe2+ are considered as potent oxidative damage inducers. This type of oxidative injury is comparable to that of ¦Â amyloid peptide (¦ÂA) on the brain of Alzheimer¡¯s disease patients. In our experimental model synaptosomes obtained from adult  Wistar rats were exposed to FeSO4 (50 ¦ÌM)  for different periods of time ( 5, 30 and 60 min) and viability parameters and the state of different signal transduction pathways were measured.  Mitochondrial function, glutamate uptake and plasma membrane integrity were affected by the presence of Fe2+, with respect to control conditions after 5, 30 and 60 min. of incubation.  Synaptosomes incubated in the presence of [¦Ã-32P]ATP, and anti-p85 inmunoprecipitates (IP) showed an increase in PI3K activity after 5 min of Fe2+-exposure. The increase on Akt phosphorylation in serine 473 and threonine 308 was temporally coincident with PI3K activation. Experiments carried out in the presence of sodium orthovanadate or herbimycin A indicated the involvement of tyrosine phosphorylation in PI3K activation induced by Fe2+. IPs with cSrc demonstrated a strong association between Akt, p Akt and this tyrosine kinase induced by oxidative stress. The downstream Akt effector, GS3K was also phosphorylated after 5 and 30 min of iron exposure and this phosphorylation was inhibited by LY294002. Additionally, Erk activation was observed after 5 and 60 min of insult exposure, but only the latter activation was PI3K dependent. Our results demonstrate that oxidative stress triggers the activation of different synaptic signaling pathways  such as  PI3K/Akt, cSrc,GS3K and Erk.