Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight and protein S-nitrosothiols

Detcho A. Stoyanovsky, Yulia Y. Tyurina, Vladimir A. Tyurin, Deepthi Anand, Dhara N. Mandavia, David Gius, Juliana Ivanova, Bruce Pitt, Timothy R. Billiar, Valerian E. Kagan

Resultado de la investigación: Articlerevisión exhaustiva

141 Citas (Scopus)


The nitrosation of cellular thiols has attracted much interest as a regulatory mechanism that mediates some of the pathophysiological effects of nitric oxide (NO). In cells, virtually all enzymes contain cysteine residues that can be subjected to S-nitrosation, whereby this process often acts as an activity switch. Nitrosation of biological thiols is believed to be mediated by N2O3, metal-nitrosyl complexes, and peroxynitrite. 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 dihydrolipoic acid, catalyze the denitrosation of S-nitrosoglutathione, S-nitrosocaspase 3, S-nitrosoalbumin, and S-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 ESR spectrometry, potentiometric measurements, and quantification of hydroxylamine and sodium nitrite as end 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 denitrosate S-nitrosothiols less efficiently. We conclude that both thioredoxin and dihydrolipoic acid may be involved in the regulation of cellular S-nitrosothiols.

Idioma originalEnglish (US)
Páginas (desde-hasta)15815-15823
Número de páginas9
PublicaciónJournal of the American Chemical Society
EstadoPublished - nov. 16 2005
Publicado de forma externa

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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