S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates apoptosis signal-regulating kinase 1

Arch Biochem Biophys. 2004 Aug 15;428(2):198-203. doi: 10.1016/j.abb.2004.06.004.

Abstract

In the present study, we have investigated S-nitrosation of reactive thioredoxin (Trx) thiol groups in nitric oxide/superoxide system. We have found that Trx thiol groups are the targets for S-nitrosation by N2O3-like species generated in the system containing xanthine/xanthine oxidase (superoxide producing system) and DEA/NO-the *NO donating compound, however, they have shown low sensitivity to the *NO derived from DEA/NO. N2O3-dependent S-nitrosation of Trx at approximately 2-fold of NO excess compared to the superoxide amount resulted in dissociation and activation of apoptosis signal regulating kinase 1 (ASK1). However, approximately 4-fold of NO excess compared to a superoxide production preserved the level of dissociated ASK1 but decreased its activity due to the enzyme S-nitrosation.

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase Kinases / metabolism*
  • MAP Kinase Signaling System
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism
  • Nitrosation*
  • Phosphorylation
  • Precipitin Tests
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism
  • Thioredoxins / chemistry*

Substances

  • Superoxides
  • Nitric Oxide
  • Thioredoxins
  • Superoxide Dismutase
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase Kinases
  • MAP3K5 protein, human