Secretory phospholipase A2, a relationship between oxidative stress and inflammatory response?

RODRIGUEZ DIEZ, G.; GIUSTO, N.M.; SALVADOR, G.A.

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB),; 2011

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We previously characterized the involvement of phospholipase A2 (PLA2) isoforms in a model of AMD. Retinal iron exposure provoked an increase in lipid peroxidation levels, a decrease in mitochondrial function and stimulated ERK activation (SAIB 2010). We demonstrated that cytosolic PLA2 (cPLA2) participates in the generation of lipid peroxides whereas the calcium-independent isoform prevents lipid peroxidation. The purpose of this work was to demonstrate a connection between cPLA2 activation and inflammatory responses in a model of AMD. We found that U0126 (MAPKK inhibitor) inhibited the iron-induced increase of arachidonic acid release in cytosolic fractions. The expression of secretory PLA2 and its relation with cyclooxigenase-2 were also evaluated. Both enzymes were associated with microsomal membranes in an iron concentration-dependent manner. We also investigated NF-κB state as one of the main targets of inflammatory response. p65 (RelA) levels were increased in nuclear fractions from retinas exposed to iron. Our results demonstrate that PLA2 isoforms are key players in this experimental model resembling AMD and we suggest that they are connectors between iron-induced oxidative stress signaling and inflammatory responses.