Thioredoxin and thioredoxin reductase in relation to reversible S-nitrosylation.
CONCLUSIONS
Nitric oxide (NO) regulates a diverse range of cellular processes, including vasodilation, neurotransmission, and antimicrobial and anti-tumor activities. S-nitrosylation with the formation of S-nitrosothiols (RSNOs) is an important feature of NO signaling regulating protein function. In mammalian cells, glutathione (GSH), S-nitrosoglutathione reductase (GSNOR), and thioredoxin (Trx) have been identified as the major protein denitrosylases.


BACKGROUND
Human cytosolic/nuclear Trx1 in the disulfide form can be nitrosylated at Cys73 and transnitrosylate target proteins, including caspase 3. Thus, similar to GSH, which by forming S-nitrosoglutathione (GSNO) can transnitrosylate proteins, Trx can either denitrosylate or nitrosylate proteins depending on its oxidation state.


RESULTS
In this review, we discuss the regulation of cellular processes by reversible S-nitrosylation and Trx-mediated cellular homeostasis of RSNOs and S-nitrosoproteins.


CONCLUSIONS
Functions of RSNOs in vivo and their pharmacological uses have not yet been fully studied. Further investigations on the role of Trx systems in relation to biologically relevant RSNOs, their functions, and the mechanisms of denitrosylation will facilitate the development of drugs and therapies. Antioxid. Redox Signal. 18, 259-269.
Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Rajib
R
Sengupta
Arne
A
Holmgren
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D026422:S-Nitrosoglutathione / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D026403:S-Nitrosothiols; C486715:TXNIP protein, human; D009569:Nitric Oxide; D013879:Thioredoxins; D026422:S-Nitrosoglutathione; C021315:S-nitrosocysteine; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine