The role of MAPKs and PLA2 in a retinal model of neurodegeneration

RODRIGUEZ DIEZ GUADALUPE; GIUSTO NORMA; SALVADOR, GABRIELA

Puerto Madryn

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

SAIB

The role of MAPKs and PLA2 in a retinal model of neurodegeneration Rodríguez Diez, G.; Giusto, N.M; Salvador, G.A. Free iron is considered as a neurotoxic agent that generates an imbalance in cellular redox mechanisms, producing lipid peroxidation, mitochondrial damage, and cell death. Iron exposure of bovine retinas constitutes a suitable experimental model of age-related macular degeneration. In this model, we have previously reported the activation of different phospholipase A2 (PLA2) isoforms (SAIB 2009). The aim of this work, was to characterize the role of cPLA2, iPLA2 and MAPKs in retinas exposed to increasing Fe2+ concentrations (25, 200 and 800 µM). Mitochondrial function and lipid peroxidation levels (measured as MTT reduction and TBARS, respectively) were determined as markers of oxidative damage. TBARS generation increased in an iron concentration dependent manner, whereas mitochondrial function was only affected at 800 µM. This was associated with the activation of ERK1/2 and p38 MAPKs. TBARS generation was significantly decreased in the presence of ATK (iPLA2 and cPLA2 inhibitor) and BEL (iPLA2 inhibitor). ATK and BEL were able to delay ERK activation at Fe 25 µM. Results suggest that both PLA2 isoforms participate in the generation of retinal oxidative damage and also modulate MAPK activation. Supported by PIP-CONICET and Fundación Florencio Fiorini   .