title: Nitric oxide protects cardiomyocytes against tert-butyl hydroperoxide-induced formation of alkoxyl and peroxyl radicals and peroxidation of phosphatidylserine.
abstract: We studied protective effects of nitric oxide against tert-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-sensitive cis-parinaric acid. An NO-donor, (Z)-1-[N-(3-ammonio-propyl)-N-(n-propyl) amino]-diazen-1-ium-1,2-diolate], protected cardiac myocytes against tert-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.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania 15238, USA.
authors.forename: N V
authors.initials: NV
authors.lastname: Gorbunov
authors.forename: Y Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: G
authors.initials: G
authors.lastname: Salama
authors.forename: B W
authors.initials: BW
authors.lastname: Day
authors.forename: H G
authors.initials: HG
authors.lastname: Claycamp
authors.forename: G
authors.initials: G
authors.lastname: Argyros
authors.forename: N M
authors.initials: NM
authors.lastname: Elsayed
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
mesh_terms: D000438:Alcohols; D000975:Antioxidants / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects; D008956:Models, Chemical; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D019159:Nonheme Iron Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010545:Peroxides; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide
chemical_list: C111679:1-(N-(3-ammoniopropyl)-N-(n-propyl)amino)diazen-1-ium-1,2-diolate; D000438:Alcohols; D000975:Antioxidants; D001384:Azetidines; D005609:Free Radicals; D009211:Myoglobin; D019159:Nonheme Iron Proteins; D010545:Peroxides; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C059688:alkoxyl radical; C049375:perhydroxyl radical; D009569:Nitric Oxide; D020122:tert-Butylhydroperoxide