Abstract
Nitric oxide protects cells from oxidative stress through a number of direct scavenging reactions with free radicals but the effects of nitric oxide on the regulation of antioxidant enzymes are only now emerging. Using bovine aortic endothelial cells as a model, we show that nitric oxide, at physiological rates of production (1-3 nM/s), is capable of inducing the synthesis of glutathione through a mechanism involving gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase. This novel nitric oxide signalling pathway is cGMP-independent and we hypothesize that it makes an important contribution to the anti-atherosclerotic and antioxidant properties of nitric oxide.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cattle
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Cells, Cultured
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / pharmacology
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Dose-Response Relationship, Drug
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Endothelium, Vascular / metabolism*
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Enzyme Inhibitors / pharmacology
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Glutamate-Cysteine Ligase / physiology*
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Glutathione / biosynthesis*
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Isoxazoles / pharmacology
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Nitric Oxide / metabolism*
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Nitroso Compounds / pharmacology
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Time Factors
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gamma-Glutamyltransferase / physiology*
Substances
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Enzyme Inhibitors
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Isoxazoles
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Nitroso Compounds
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8-bromocyclic GMP
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Nitric Oxide
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S-nitrosopenicillamine
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gamma-Glutamyltransferase
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Glutamate-Cysteine Ligase
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Glutathione
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Cyclic GMP
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acivicin