Activation of antioxidant defense mechanism by Docosahexaenoic acid and Eicosapentaenoic acid prevents apoptosis of retina photoreceptors

AGNOLAZZA, D.L.; POLITI, L.E.; ROTSTEIN, N.P.

Huerta Grande

Congreso; II Reunion Conjunta en Neurociencias; 2010

ACTIVATION OF ANTIOXIDANT DEFENSE MECHANISMS BY DOCOSAHEXAENOIC ACID AND EICOSAEXAENOIC ACID PREVENTS APOPTOSIS OF RETINA PHOTORECEPTORS Agnolazza DL., Politi LE y Rotstein NP. Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur (UNS)-CONICET. B. Blanca, Bs. As. agnolazza@inibibb-conicet.gob.ar Oxidative stress participates in activating the apoptosis of photoreceptors (PRs) in retinal neurodegenerative diseases. We have shown that docosahexaenoic acid (DHA), the major retina polyunsaturated fatty acid, protects PRs from apoptosis induced by the oxidant paraquat (PQ) by activating the ERK pathway. Here we investigated if other fatty acids had a similar protective effect and if this protection involved the activation of antioxidant defense mechanisms in PRs. Rat retina neuronal cultures were supplemented with EPA (eicosapentaenoic acid), DHA, Palmitic, Oleic and Arachidonic acids and treated at day 3 with PQ. Only EPA and DHA prevented PR apoptosis. As EPA is a DHA precursor, we investigated whether it protected PRs by itself or through its conversion to DHA. When we evaluated the fatty acid composition of EPA-supplemented neurons, EPA levels remained constant but DHA content significantly increased. Addition of hydrogen peroxide (H2O2) induced PR apoptosis and increased the production of reactive oxygen species (ROS), measured by DCFDA. DHA and EPA prevented PR apoptosis and decreased ROS formation after H2O2 addition. This work suggests EPA protects PRs through its conversion to DHA and implies that DHA and EPA activate antioxidant defense mechanisms to rescue PRs.