Activation of phospholipase A2 in a retinal model of neurodegeneration

RODRÍGUEZ DIEZ, GUADALUPE; URANGA, ROMINA MARÍA; MATEOS, MELINA; GIUSTO, NORMA MARÍA; SALVADOR, GABRIELA ALEJANDRA

San Miguel de Tucumán, Tucumán, Argentina.

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Transitions metals, considered as neurotoxic agents, generate an unbalance in cellular redox mechanisms, producing lipid peroxidation, mitochondrial damage, and cell death. In this work, we characterized the participation of phospholipase A2 (PLA2) in an experimental model of age-related macular degeneration (AMD). For this purpose, we used bovine retinas exposed to increasing Fe2+ concentrations (25, 200 and 800 microM), and we determined mitochondrial function (measured as MTT reduction) and lipid peroxidation levels (determined by TBARS). The activity of cPLA2 and iPLA2 was measured using palmitoyl-[14C]arachidonoyl- and [14C]dipalmitoyl-phosphatidylcholine as exogenous substrates, respectively. Fe2+ induced a concentration-dependent decrease in mitochondrial function after 1 h of Fe2+-exposure (36% and 45% of MTT reduction for 200 and 800 microM, respectively). TBARS generation was significantly increased at all the concentrations assayed both in membrane and soluble fractions. This was associated with the activation of ERK1/2 and tyrosine kinases. Microsomal and cytosolic cPLA2 activities were stimulated by 30% and 200% after 1 h of metal exposure. iPLA2 activity was stimulated by 30% with respect to controls. Results suggest that this is an appropriate model to study the role of iron-induced neurotoxicity and to evaluate the role of PLA2 in an experimental model of AMD.