The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase.
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.
Moellering
D
D
Department of Pathology, University of Alabama at Birmingham, 35294-0019, USA.
Mc Andrew
J
J
Patel
R P
RP
Forman
H J
HJ
Mulcahy
R T
RT
Jo
H
H
Darley-Usmar
V M
VM
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*
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