Metabolism of S-nitrosoglutathione by endothelial cells.
S-nitrosoglutathione (GSNO) is an inhibitor of platelet aggregation and has also been shown to protect the ischemic heart from reperfusion-mediated injury. Although GSNO is often used in cell culture as a source of nitric oxide, the mechanisms of GSNO metabolism are not well established. We show here that GSNO decomposition by bovine aortic endothelial cells has an absolute dependence on the presence of cystine in the cell culture medium. In addition, GSNO decay is inhibited by diethyl maleate, an intracellular glutathione scavenger, but not by buthionine sulfoximine, a glutathione synthesis inhibitor. This indicates that thiols in general, rather than specifically glutathione, are the major factors that influence GSNO decay. Only 40% of the nitroso group of GSNO could be recovered as nitrite/nitrate, suggesting that the primary route of GSNO decay is reductive and that nitric oxide is only a minor product of GSNO decay. We conclude that the intracellular thiol pool causes the reduction of extracellular disulfides to thiols, which then directly reduce GSNO.
Zeng
H
H
Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Spencer
N Y
NY
Hogg
N
N
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D001790:Blood Physiological Phenomena; D002417:Cattle; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003553:Cystine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D009994:Osmolar Concentration; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase / Q000494:pharmacology
D002614:Chelating Agents; D009566:Nitrates; D009573:Nitrites; D009603:Nitroso Compounds; D009861:Onium Compounds; D003553:Cystine; D026422:S-Nitrosoglutathione; C007517:diphenyleneiodonium; D013482:Superoxide Dismutase; D005978:Glutathione