NITRIC-OXIDE PROTECTS CARDIOMYOCYTES AGAINST TERT-BUTYL HYDROPEROXIDE-INDUCED FORMATION OF ALKOXYL AND PEROXYL RADICALS AND PEROXIDATION OFPHOSPHATIDYLSERINE

We studied protective effects of nitric oxide against tert-butyl hydro peroxide-induced oxidative damage to cardiac myocytes. Two distinct fr ee radicals species-alkoxyl radicals associated with nonheme iron cata lytic sites and myoglobin protein-centered peroxyl radicals-were found in low-temperature EPR spectra of cardiac myocytes exposed to t-BuOOH . The t-BuOOH-induced radical formation was accompanied by site-specif ic oxidative stress in membrane phospholipids (peroxidation of phospha tidylserine) assayed by fluorescence HPLC after metabolic labeling of cell phospholipids with oxidation-sensitive cis-parinaric acid. An NO- donor, pyl)-N-(n-propyl)amino]-diazen-1-ium-1,2-diolate], protected ca rdiac myocytes against tert-butyl hydroperoxide-induced: (i) formation of non-protein-and protein-centered free radical species and (ii) con comitant peroxidation of phosphatidylserine. Thus nitric oxide can act as an effective antioxidant in live cardiomyocytes. (C) 1998 Academic Press.