Nitric oxide and the thioredoxin system: A complex interplay in redox regulation

Background The free radical nitric oxide (NO) and the thiol oxidoreductase thioredoxin (Trx) play essential roles in cellular redox regulation. Recent biochemical and cellular studies have revealed a complex thiol-dependent crosstalk between NO and Trx that modulates multiple redox-dependent pathways. Scope of review This review aims to discuss recent progress, as well as the remaining questions, regarding the interaction and cross regulation between NO and Trx in cellular function and dysfunction. Major conclusions The importance and ubiquity of NO-mediated S-nitrosylation of protein thiols as a signaling mechanism is increasingly recognized as is the central role of Trx in regulating S-nitrosylation processes. By denitrosylating diverse protein substrates, Trx plays an active role in attenuating NO signaling as well as in ameliorating nitrosative stress. Yet, at the same time, Trx can also support the activity of NO synthases, thus promoting NO production and its downstream effects. Finally, NO can reciprocally modulate the redox activity of Trx and Trx reductase. General significance Further elucidation of the crosstalk between NO and Trx will be important for an improved understanding of the effects of reactive oxygen and nitrogen species on cellular signaling and function.