Activation of phospholipase A2 in a retinal model of neurodegeneration.

RODRIGUEZ DIEZ, G; URANGA ROMINA; MATEOS MELINA; GIUSTO NORMA; SALVADOR GABRIELA

San Miguel de Tucuman, Argentina. LI-P20 Biocell.

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

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

Activation of phospholipase A2 in a retinal model of neurodegeneration. Rodriguez-Diez,G., Uranga, R., Mateos, M., Giusto,N., Salvador,G. 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 800µM) 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-phospatidylcholine as exogenous substrates, respectively. Fe2+ induced a concentration-dependent decrease in mitochondrial function after 1h exposure (36 % and 45 % of MTT reduction with respect to controls). TBARS generation 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 800 % after 1 h of metal exposure. iPLA2 activity was stimulated by 30 % with respect to controls. Results suggest that this is a good model to study the role of iron-induced neurotoxicity and to evaluate the role of PLA2 in a experimental model of AMD.