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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / metabolism*
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Dithiothreitol / pharmacology
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Electron Transport Complex IV / metabolism
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Glucose / pharmacology*
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Glutathione / pharmacology*
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Kinetics
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Molsidomine / analogs & derivatives
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Molsidomine / pharmacology
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Nitrates / pharmacology*
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Nitric Oxide / pharmacology*
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Oxygen Consumption / drug effects*
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Rats
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Submitochondrial Particles / drug effects
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Submitochondrial Particles / metabolism*
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Superoxide Dismutase / pharmacology
Substances
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Nitrates
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peroxynitric acid
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Nitric Oxide
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linsidomine
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Molsidomine
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Superoxide Dismutase
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Electron Transport Complex IV
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Glutathione
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Glucose
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Dithiothreitol