Secretory Phospholipase A2, A Relationship Between Oxidative Stress And Inflammatory Response?

RODRIGUEZ DIEZ GUADALUPE; GIUSTO NORMA; SALVADOR, GABRIELA

San Luis

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

Saib

Abstract SAIB 2011 Secretory  phospholipase A2, a relationship between oxidative stress and inflammatory response[FC1] ? Rodríguez Diez, G., Giusto, N.M. Salvador, G.A. Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-UNS-CONICET[FC2] ) 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 also 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) reverted the iron-induced increase of arachidonic acid release in cytosolic fractions. The expression of secretory PLA2 (sPLA2) and its relation with cyclooxigenase-2 (COX-2) were also evaluated. Both enzymes were associated with microsomal membranes as iron concentration increased. We also evaluated NF-k[FC3] B state as one of main targets of inflammatory response. p65 (RelA) levels were increased in nuclear fractions in an iron concentration dependent-manner. 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.