AKT/GSK3Β SIGNALING DURING IRON-INDUCED NEUROTOXICITY IN HT22 HIPPOCAMPAL NEURONS

URANGA, ROMINA; RODRIGUEZ DIEZ GUADALUPE; GIUSTO NORMA; SALVADOR GABRIELA

Puerto Madryn

Congreso; XLVI Reunión Anual de la SAIB; 2010

SAIB

AKT/GSK3Β SIGNALING DURING IRON-INDUCED NEUROTOXICITY IN HT22 HIPPOCAMPAL NEURONS Uranga, R.M., Rodriguez-Diez, G; Giusto, N.M., Salvador, G.A. Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET), B. Blanca, Argentina.   Akt and glycogen synthase kinase 3β (GSK3β) are key components of signaling pathways involved in synaptic plasticity and neuronal survival. The specific aims of this work were: i) to characterize  an iron-induced neurodegeneration model and ii) to study the participation of Akt and GSK3β in the signaling events triggered during neuronal degeneration induced by oxidative injury. For this purpose, a cell line of murine hippocampal neurons, HT22, was exposed to increasing Fe2+ concentrations (25, 50, 100 and 200 µM) for 24h. Cell viability, morphology, lipid peroxidation and superoxide dismutase expression were evaluated for determining the extent of neuronal injury. Mitochondrial function (MTT reduction) was significantly reduced in the presence of 50, 100 and 200 µM Fe. The decrease in MTT reduction strongly correlated with the changes in cellular morphology. Moreover, the expression of superoxide dismutase diminished after iron exposure. Based on previous experimental data we defined that 24 h exposure to iron (25 and 50 µM)  was enough to cause a mild neuronal oxidative injury. Under these experimental conditions  both Akt and GSK3β phosphorylation were increased. We demonstrate here that iron neurotoxicity in hippocampal neurons activates Akt pathway promoting GSK3β inhibition under mild oxidative injury