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

Abstract

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 (PLA ) isoforms in a model of AMD. Retinal iron exposure2 provoked an increase in lipid peroxidation levels, a decrease in mitochondrial function and stimulated ERK activation (SAIB 2010). We demonstrated that cytosolic PLA (cPLA ) participates in2 2 the generation of lipid peroxides whereas the calcium-independent isoform prevents lipid peroxidation. The purpose of this work was to demonstrate a connection between cPLA activation and2 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 PLA and its relation with cyclooxigenase-2 were also2 evaluated. Both enzymes were associated with microsomal membranes in an iron concentration-dependent manner. We also investigated NF-kB state as one of 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.