Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose.
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.
Lizasoain
I
I
The Wellcome Research Laboratories, Kent, U.K.
Moro
M A
MA
Knowles
R G
RG
Darley-Usmar
V
V
Moncada
S
S
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
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