Redox regulatory and anti-apoptotic functions of thioredoxin depend on S-nitrosylation at cysteine 69

Nat Cell Biol. 2002 Oct;4(10):743-9. doi: 10.1038/ncb851.

Abstract

Thioredoxin 1 (Trx) is a known redox regulator that is implicated in the redox control of cell growth and apoptosis inhibition. Here we show that Trx is essential for maintaining the content of S-nitrosylated molecules in endothelial cells. Trx itself is S-nitrosylated at cysteine 69 under basal conditions, and this S-nitrosylation is required for scavenging reactive oxygen species and for preserving the redox regulatory activity of Trx. S-nitrosylation of Trx also contributes to the anti-apoptotic function of Trx. Thus, Trx can exert its complete redox regulatory and anti-apoptotic functions in endothelial cells only when cysteine 69 is S-nitrosylated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / physiology
  • Apoptosis / physiology*
  • Cells, Cultured
  • Cysteine / metabolism*
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Endothelium / cytology
  • Endothelium / enzymology*
  • Enzyme Inhibitors / pharmacology
  • Free Radical Scavengers / metabolism
  • Gene Expression Regulation, Enzymologic / physiology
  • Genetic Vectors / genetics
  • Humans
  • Mutation / genetics
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitrogen Compounds / metabolism
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Sulfur / metabolism
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Nitrogen Compounds
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Thioredoxins
  • Sulfur
  • Nitric Oxide Synthase
  • Cysteine