MODULATION OF RADIATION-INDUCED LIPID-PEROXIDATION BY PHOSPHOLIPASE A(2) AND CALMODULIN ANTAGONISTS - RELEVANCE TO DETOXIFICATION

Ghost membranes prepared from erythrocytes of Swiss albino mice were i rradiated with 0.9 Gy s(-1). Lipid peroxidation initiated by ionizing radiation was enhanced by phospholipase A(2), and required both phosph olipase A(2) and GSH peroxidase for consecutive action to convert fatt y acid peroxides into corresponding alcohols. The ability of phospholi pase A(2) to enhance lipid peroxidation was increased in presence of C a2+. However, in combination, phospholipase A(2) and GSH-peroxidase we re effective in inhibiting lipid peroxidation. These findings show tha t free fatty acid peroxides considerably increase the peroxidation. Ca lmodulin antagonists inhibit lipid peroxidation and decrease the radia tion induced release of Ca2+ from the membranes. Our results suggest t he importance of Ca2+ dependent phospholipase A(2) in detoxification o f fatty acid peroxides in the membranes. It is quite possible that sca venging of free radicals by calmodulin antagonists lower the formation of hydroperoxides, resulting in the decrease in activity of phospholi pase A(2). Alternatively, decrease in Ca2+ release due to the calmodul in antagonists might have affected the activity of phospholipase A(2). Our observations might be of considerable significance in the underst anding of post irradiation effect on biological membranes.