Thioredoxin and thioredoxin binding protein 2 in the liver.

Thioredoxin (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- and constitutes a major thiol reducing system. TRX protects cells from stress-induced damage through antioxidative, antiapoptotic, and anti-inflammatory effect. In animal models, thioacetamide (TAA)-induced acute hepatitis and TAA-induced liver fibrosis was attenuated in TRX transgenic (TRXTG) mice. Plasma level of TRX is a good marker for hepatitis and nonalcoholic steatohepatitis (NASH) in human patients. Recently, we identified TRX binding protein 2 (TBP2) in a yeast two-hybrid screening. TBP2 regulates both the expression and reducing activity of TRX as well as cell growth. TBP2 knockout (TBP2KO) mice showed disorder in lipid metabolism. TBP2 plays a multiple role on cell growth and lipid and glucose metabolism. Thus, TRX and TBP2 play important roles in the pathophysiology of liver diseases, including NASH, indicating that ratio of TRX and TBP2 expression could be a novel marker of liver diseases like NASH.