Thioredoxin: a multifunctional antioxidant enzyme in kidney, heart and vessels

Purpose of review Recent studies indicate that an imbalance in cell redox state alters multiple cell pathways that may contribute to the pathogenesis of cardiovascular disorders including hypertension and renal failure. Recent findings The thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH) is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. Thioredoxin plays an essential role in cell function by limiting oxidative stress directly via antioxidant effects and indirectly by protein–protein interactions with key signaling molecules such as thioredoxin-interacting protein (TXNIP). Examples include the findings that hyperglycemia and diabetes induce TXNIP and decrease thioredoxin activity, while steady blood flow decreases TXNIP and increases thioredoxin activity. Summary Based on these findings we propose that thioredoxin and its endogenous regulators represent important future targets to develop clinical therapies for diseases associated with oxidative stress. Abbreviations ASK1: apoptosis signal-regulating kinase 1; JNK: c-Jun N-terminal kinase; PDGF: platelet-derived growth factor; ROS: reactive oxygen species; SHR: spontaneously hypertensive rat; SHRSP: stroke-prone spontaneously hypertensive rat; TXNIP: thioredoxin-interacting protein; VCAM1: vascular cell-adhesion molecule 1; VSMC: vascular smooth muscle cell.