title: Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose.
abstract: Nitric oxide (NO) and peroxynitrite both inhibit respiration by brain submitochondrial particles, the former reversibly at cytochrome c oxidase, the latter irreversibly at complexes I-III. Both GSH (IC50 =10 microM) and glucose (IC50 = 8 mM) prevented inhibition of respiration by peroxynitrite (ONOO-), but neither glucose (100 mM) nor GSH (100 microM) affected that by NO. Thus, unless ONOO- is formed within mitochondria it is unlikely to inhibit respiration in cells directly, because of reactions with cellular thiols and carbohydrates. However, the reversible inhibition of respiration cytochrome c oxidase by NO is likely to occur (e.g. in the brain during ischaemia) and could be responsible for cytotoxicity.
authors.affiliation: The Wellcome Research Laboratories, Kent, U.K.
authors.forename: I
authors.initials: I
authors.lastname: Lizasoain
authors.forename: M A
authors.initials: MA
authors.lastname: Moro
authors.forename: R G
authors.initials: RG
authors.lastname: Knowles
authors.forename: V
authors.initials: V
authors.lastname: Darley-Usmar
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
chemical_list: D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; D005978:Glutathione; D005947:Glucose; D004229:Dithiothreitol