Copper overload triggers antioxidant defenses imbalance in hippocampal ht22 neurons.

IGLESIAS GONZALEZ, P; URANGA, R; SALVADOR, G

Mar del Plata

Congreso; LI Reunion ANual de SAIB; 2015

SAIB

COPPER OVERLOAD TRIGGERS ANTIOXIDANT DEFENSES IMBALANCE INHIPPOCAMPAL HT22 NEURONSIglesias Gonzalez PA, Uranga RM, Salvador GA.INIBIBB-UNS-CONICET Bahia Blanca-Argentina. E-mail: pablo_igl_@hotmail.comCopper (Cu)-induced oxidative stress has been involved in the pathogenesis of several neurodegenerative diseasessuch as Alzheimer?s disease and related disorders. In this work, we characterized the response of hippocampalneurons to Cu overload and we also studied the signaling pathways involved in the regulation of antioxidant defensesand neuronal survival. HT22 hippocampal neurons incubated with increasing Cu2+ concentrations (100-250 μM)showed decreased glutathione (GSH) levels and GSH peroxidase expression, and increased expression levels of therate limiting step enzyme for GSH synthesis, glutamate cysteine ligase (GCL). Cu-induced imbalance in antioxidantdefenses generated an increase in reactive oxygen species content. As a result of the increased pro-oxidant conditions,neuronal damage was evidenced by mitochondrial dysfunction and increased lipid peroxidation levels. Mitochondrialfunction was even more affected by pharmacological inhibition of MAPK (U0126) and PI3K (LY294002) pathways. BIOCELL 39 (Suppl. 2) 2015Both effector kinases, ERK1/2 and Akt, respectively showed a differential neuronal localization and expression levelsin neurons exposed to Cu-injury. Our results show that Cu-induced neuronal injury is generated by an imbalance incellular GSH metabolism and that neuronal survival depends on PI3K/Akt and ERK1/2 mediated pathways.