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Nature Cell Biology 4, 743–749 (1 October 2002) | doi:10.1038/ncb851

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

Judith Haendeler , J|[ouml]|rg Hoffmann , Verena Tischler , Bradford C. Berk , Andreas M. Zeiher & Stefanie Dimmeler

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.