Nitric Oxide Protects Cardiomyocytes againsttert-Butyl Hydroperoxide-Induced Formation of Alkoxyl and Peroxyl Radicals and Peroxidation of Phosphatidylserine
摘要
We studied protective effects of nitric oxide againsttert-butyl hydroperoxide-induced oxidative damage to cardiac myocytes. Two distinct free radicals species—alkoxyl radicals associated with non-heme iron catalytic 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-specific oxidative stress in membrane phospholipids (peroxidation of phosphatidylserine) assayed by fluorescence HPLC after metabolic labeling of cell phospholipids with oxidation-sensitivecis-parinaric acid. An NO-donor, (Z)-1-[N-(3-ammonio-propyl)-N-(n-propyl)amino]-diazen-1-ium-1,2-diolate], protected cardiac myocytes againsttert-butyl hydroperoxide-induced: (i) formation of non-protein- and protein-centered free radical species and (ii) concomitant peroxidation of phosphatidylserine. Thus nitric oxide can act as an effective antioxidant in live cardiomyocytes.