Abstract
We examined the ability of peroxynitrite and other .NO-derived oxidants to inhibit creatine kinase (CK). Peroxynitrite potently inhibited CK activity and depleted protein thiols. The rate constant for this reaction was 8.85x10(5) M(-1) s(-1). Glutathione did not reactivate CK activity nor did it regenerate protein thiol content. In contrast, glutathione reactivated CK, and regenerated protein thiols, after inhibition by either .NO or oxidized glutathione (GSSG). Peroxynitrite did not irreversibly inhibit CK after it had been treated with GSSG to block protein thiols. We conclude that thiol oxidation is a critical event leading to inactivation of CK by peroxynitrite.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetonitriles / pharmacology
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Animals
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Creatine Kinase / antagonists & inhibitors*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Enzyme Reactivators / pharmacology
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Glutathione / pharmacology
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Glutathione Disulfide / pharmacology
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Kinetics
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Molsidomine / analogs & derivatives
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Molsidomine / pharmacology
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Morpholines / pharmacology
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Nitrates / pharmacology*
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Nitric Oxide / physiology
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Oxidants / pharmacology*
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Rabbits
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Sulfhydryl Compounds / analysis
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Superoxides
Substances
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Acetonitriles
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Enzyme Inhibitors
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Enzyme Reactivators
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Morpholines
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Nitrates
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Oxidants
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Sulfhydryl Compounds
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Superoxides
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SIN 1C
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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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Creatine Kinase
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Glutathione
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Glutathione Disulfide