Redox control of cellular function by thioredoxin; a new therapeutic direction in host defence.
Compelling evidence has suggested that oxidative stress mediates various cellular responses, and control of reduction/oxidation (redox) is important in maintaining the homeostasis of an organism. The thioredoxin (TRX) system, as well as the glutathione system, is one of the key systems in controlling cellular redox status. TRX is a small ubiquitous protein with the redox-active site sequence -Cys-Gly-Pro-Cys-. It has been demonstrated to be a multifunctional protein, which has regulatory roles in cellular signaling and gene transcription in addition to cytoprotective activities through the quenching of reactive oxygen species. Various oxidative stimuli, such as UV irradiation, cytokines and some chemicals, promptly induce the expression of TRX. Overexpression of TRX correlates with a wide variety of oxidative stress conditions and, in some cases, TRX has shown promising effects for clinical use, for instance in the attenuation of tissue injury in ischemia reperfusion models. The modulation of TRX functions in association with other redox-regulatory molecules should give us a new therapeutic strategy in the treatment of oxidative stress-mediated disorders and diseases.
Nishinaka
Y
Y
Department of Biological Responses, Institute for Virus Research, Kyoto University, Sakyo, Japan.
Nakamura
H
H
Masutani
H
H
Yodoi
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use*
D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D013879:Thioredoxins