Glutathionylation of human thioredoxin: A possible crosstalk between the glutathione and thioredoxin systems
AUTOR(ES)
Casagrande, Simona
FONTE
The National Academy of Sciences
RESUMO
To identify proteins undergoing glutathionylation (formation of protein-glutathione mixed disulfides) in human T cell blasts, we radiolabeled the glutathione pool with 35S, exposed cells to the oxidant diamide, and analyzed cellular proteins by two-dimensional electrophoresis. One of the proteins undergoing glutathionylation was identified by molecular weight, isoelectric point, and immunoblotting as thioredoxin (Trx). Incubation of recombinant human Trx with glutathione disulfide or S-nitrosoglutathione led to the formation of glutathionylated Trx, identified by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. The glutathionylation site was identified as Cys-72. Glutathionylation of rhTrx abolished its enzymatic activity as insulin disulfide reductase in the presence of NADPH and Trx reductase. Activity was, however, regained with sigmoidal kinetics, indicating a process of autoactivation due to the ability of Trx to de-glutathionylate itself. These data suggest that the intracellular glutathione/glutathione disulfide ratio, an indicator of the redox state of the cell, can regulate Trx functions reversibly through thiol-disulfide exchange reactions.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125000Documentos Relacionados
- Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems
- Cross-talk between the insulin and angiotensin signaling systems.
- Escherichia coli thioredoxin: a subunit of bacteriophage T7 DNA polymerase.
- Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system.
- Mitochondrial and Nuclear Localization of a Novel Pea Thioredoxin: Identification of Its Mitochondrial Target Proteins1[W]