Redox regulatory and anti-apoptotic functions of thioredoxin depend on S-nitrosylation at cysteine 69.
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.
Haendeler
Judith
J
Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Hoffmann
Jörg
J
Tischler
Verena
V
Berk
Bradford C
BC
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
D000595:Amino Acid Sequence / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004727:Endothelium / Q000166:cytology / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017672:Nitrogen Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017672:Nitrogen Compounds; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013879:Thioredoxins; D013455:Sulfur; D019001:Nitric Oxide Synthase; D003545:Cysteine