Thioredoxin and Lipoic Acid Catalyze the Denitrosation of Low Molecular Weight and Protein S-Nitrosothiols
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- 作者：Detcho A. Stoyanovsky ; Yulia Y. Tyurina ; Vladimir A. Tyurin ; Deepthi Anand ; Dhara N. Mandavia ; David Gius ; Juliana Ivanova ; Bruce Pitt ; Timothy R. Billiar ; and Valerian E. Kagan
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：November 16, 2005
- 年：2005
- 卷：127
- 期：45
- 页码：15815 - 15823
- 全文大小：189K
- 年卷期：v.127,no.45(November 16, 2005)
- ISSN：1520-5126
文摘
The nitrosation of cellular thiols has attracted much interest as a regulatory mechanism thatmediates some of the pathophysiological effects of nitric oxide (NO). In cells, virtually all enzymes containcysteine residues that can be subjected to S-nitrosation, whereby this process often acts as an activityswitch. Nitrosation of biological thiols is believed to be mediated by N2O3, metal-nitrosyl complexes, andperoxynitrite. To date, however, enzymatic pathways for S-denitrosation of proteins have not been identified.Herein, we present experimental evidence that two ubiquitous cellular dithiols, thioredoxin and dihydrolipoicacid, catalyze the denitrosation of S-nitrosoglutathione, S-nitrosocaspase 3, S-nitrosoalbumin, andS-nitrosometallothionenin to their reduced state with concomitant generation of nitroxyl (HNO), the one-electron reduction product of NO. In these reactions, formation of NO and HNO was assessed by ESRspectrometry, potentiometric measurements, and quantification of hydroxylamine and sodium nitrite asend reaction products. Nitrosation and denitrosation of caspase 3 was correlated with its proteolytic activity.We also report that thioredoxin-deficient HeLa cells with mutated thioredoxin reductase denitrosateS-nitrosothiols less efficiently. We conclude that both thioredoxin and dihydrolipoic acid may be involvedin the regulation of cellular S-nitrosothiols.