Akt/GSK3B signaling during iron-induced neurotoxicity in HT22 hippocampal neurons

URANGA RM; RODRIGUEZ DIEZ G; GIUSTO NM; SALVADOR GA.

Puerto Madryn, Chubut, Argentina.

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

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

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 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 24 h. Cell viability, morphology and lipid peroxidation were evaluated for determining the extent of neuronal injury. Cell viability, measured as MTT reduction, was significantly reduced in the presence of 50, 100 and 200 µM Fe2+. HT22 cell morphology, evaluated by phase-contrast microscopy, showed evident morphological alterations including rounded cell body with a decreased number of cell projections. The decrease in MTT reduction strongly correlated with the changes in cellular morphology. Based on these data we defined that 24-h exposure to iron (25 and 50 µM) caused a mild oxidative injury. Under these experimental conditions both Akt and GSK3β phosphorylation were increased. We conclude that iron-induced neurotoxicity activates Akt promoting GSK3β inhibition under mild oxidative injury in hippocampal neurons.