The induction of GSH synthesis by nanomolar concentrations of NO in endothelial cells: a role for γ‐glutamylcysteine synthetase and γ‐glutamyl transpeptidase

FEBS Letters

Mulcahy, R.Timothy³  Forman, Henry Jay¹  Jo, Hanjoong²  Moellering, Douglas²  Darley-Usmar, Victor M²  Patel, Rakesh P²  Mc Andrew, Joanne² 

[1] University of Southern California, 1985, Zonal Ave., Los Angeles, CA 90033, USA;Department of Pathology, Molecular and Cellular Division, University of Alabama at Birmingham, Volker Hall Room GO38, 1670 University Boulevard, Birmingham, AL 35294-0019, USA;Department of Human Oncology, University of Wisconsin-Madison, K4/316 CSC, 600 Highland Ave., Madison, WI 53792, USA

关键词: Glutathione;    Endothelial cell;    Nitric oxide;    γ-Glutamylcysteine synthetase;    Atherosclerosis;    γ-Glutamyl transpeptidase;    NO;    nitric oxide;    SNAP;    S-nitrosopenicillamine;    BAEC;    bovine aortic endothelial cell;    GCS;    γ-glutamylcysteine synthetase;    γ-GT;    γ-glutamyl transpeptidase;    GSH;    reduced glutathione;    GSSG;    oxidized glutathione;    tGSH;    total glutathione;    DTPA;    diethylene triamine penta acetic acid;    DEPC;    diethyl pyrocarbonate;    NOS;    nitric oxide synthase;    ODQ;    1H-(1;    2;    4) oxadiazolo(4;    3;    -α) quinoxalin-1-one;   

DOI  :  10.1016/S0014-5793(99)00371-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 γ-glutamylcysteine synthetase and γ-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.

【 授权许可】

Unknown