title: The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase.
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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 35294-0019, USA.
authors.forename: D
authors.initials: D
authors.lastname: Moellering
authors.forename: J
authors.initials: J
authors.lastname: Mc Andrew
authors.forename: R P
authors.initials: RP
authors.lastname: Patel
authors.forename: H J
authors.initials: HJ
authors.lastname: Forman
authors.forename: R T
authors.initials: RT
authors.lastname: Mulcahy
authors.forename: H
authors.initials: H
authors.lastname: Jo
authors.forename: V M
authors.initials: VM
authors.lastname: Darley-Usmar
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000502:physiology*; D005978:Glutathione / Q000096:biosynthesis*; D007555:Isoxazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007555:Isoxazoles; D009603:Nitroso Compounds; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C024942:S-nitrosopenicillamine; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D006152:Cyclic GMP; C006303:acivicin