GSK3and Erk are activated downstream of PI3K in synaptic endings during oxidative injury¡¡À. XLIV Reuni¡§®n Anual de la Sociedad Argentina de Investigaci¡§®n en Bioqu¡§ªmica y Biolog¡§ªa Molecular (SAIB), 8 al 11 de noviembre de 2008, Villa Carlos Paz, C¡§®rdoba, A

URANGA ROMINA; GIUSTO NORMA; SALVADOR GABRIELA

Villa Carlos Paz, Cordoba

Congreso; XLIV Reuni¡§®n Anual de la Sociedad Argentina de Investigaci¡§®n en Bioqu¡§ªmica y Biolog¡§ªa Molecular (SAIB), 8 al 11 de noviembre de 2008,; 2008

SAIB

GSK3¦Â and Erk are activated downstream of PI3K in synaptic endings during oxidative injury Uranga, R.M. 1, 2, 3, Giusto, N.M. 1, 2, 3, Salvador, G.A. 1, 2, 3 1 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. Iron induced oxidative injury is comparable to that of ¦Â-amyloid peptide on the brain of Alzheimer¡¯s disease patients. Our purpose was to evaluate the state of PI3K pathway and its downstream effectors Akt and GSK3¦Â in cerebral cortex synaptosomes exposed to Fe2+ (50 ¦ÌM) for different periods of time (5, 30 and 60 min). The increase in Akt phosphorylation in serine 473 and threonine 308 was temporally coincident with PI3K activation (5 min). GSK3¦Â, the downstream effector of Akt, was also phosphorylated after 5 and 30 min of iron exposure and this phosphorylation was inhibited by LY294002. Additionally, Erk activation was also observed after 5 and 30 min of insult exposure, and this activation was PI3K-dependent. Immunoprecipitations carried out with anti-cSrc demonstrated a strong association between activated Akt and this tyrosine kinase induced by oxidative stress. Our results demonstrate that oxidative stress triggers the activation of different synaptic signaling pathways that operate downstream PI3K/Akt.