ABSTRACT
The thioredoxin (TRX) and glutathione (GSH) systems regulate the cellular redox (reduction=oxidation) status. Thioredoxin is a ubiquitous small multifunctional molecule that has a redox-active disulfide=dithiol within the conserved –Cys-Gly-Pro-Cys-sequence. It is a stress-inducible protein, and exerts intracellular and extracellular functions. Intracellularly, TRX scavenges reactive oxygen species (ROS) and protects cells against oxidative stress. It also regulates
various signal transduction pathways, including proliferation, apoptosis, and gene expressions through the proteinprotein or protein-nucleic acid interaction. It translocates from cytosol to nucleus upon stress and augments the DNA binding activity of several transcription factors. Extracellularly, TRX suppresses the inflammation by regulating the neutrophil activation and extravasation and exerts the cytoprotective activity. Thioredoxin-transgenic mice (TRX-Tg mice) show the milder tissue damage or injury than the control mice in several oxidative stress-associated disease models. Moreover, the administration of recombinant human TRX (rhTRX) ameliorates the acute lung injury (ALI) associated with neutrophil infiltration in mice. Therefore, aiming at the clinical application, the translational research project is in process using rhTRX as a therapeutic drug of ALI=acute respiratory distress syndrome (ARDS). Accumulating evidence suggests that administrating rhTRX can be a novel modality regulating cellular redox on the several severe diseases or complications related to inflammation and oxidative stress.
