Thioredoxin and thioredoxin binding protein 2 in the liver

Abstract

SummaryThioredoxin (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 stressinduced damage through antioxidative, antiapoptotic, and antiinflammatory 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.2008 IUBMB IUBMB Life, 60(10): 656-660, 2008

Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets

“…This is especially intriguing for mouse serum, in which the Trx1 levels are extremely low (1–10 nM) [2]. Although Trx1 is secreted as full-length and truncated forms [19,20], we only detected the full-length form, suggesting that the truncated Trx1 form is either much less abundant or it is not trapped by the TR1 column. A 55 kDa band was also observed in the rat brain sample that corresponds to TR1 (see above).…”

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

“…In the present study, a rat model of TAA-induced liver fibrosis and cirrhosis was 64 used to identify urinary protein biomarkers related to the developmental process (1 week, supernatant was removed, the pellets were re-suspended with lysis buffer (8 M urea, 2 M 120 thiourea, 25 mM dithiothreitol (DTT) and 50 mM Tris) [36] . Protein concentrations were 121 measured using the Bradford method.…”

“…Carbonic anhydrase 3 is also a 345 biomarker of liver injury [62] . Thioredoxin has a potential to attenuate liver fibrosis via 346 suppressing oxidative stress and inhibiting proliferation of stellate cells [63] and plays 347 important roles in the pathophysiology of liver diseases [64] . Overexpression of 348 thioredoxin has been reported to prevent TAA-induced hepatic fibrosis in mice [63] .…”

Dynamic expression of hepatic thioredoxin mRNA in rats with non‐alcoholic fatty liver disease

“…14 Since Trx is a redox-sensitive molecule, 15 serum Trx levels are believed to be a clinically useful marker for oxidative stress, and the ratio of expression of Trx and Trx binding protein 2, which is an endogenous inhibitor of Trx, could be a novel marker of liver diseases like NASH. 16 Sumida et al, 17 and Nakashima et al 18 reported that serum Trx concentrations were obviously elevated in patients with NASH compared with the concentrations in patients with simple steatosis or in healthy volunteers. Mitsuyoshi et al 6 reported that the levels of Trx genes were significantly higher in NAFLD patients than in a control group and tended to increase as the stage progressed.…”

“…Hepatic Trx expression may exert a therapeutic effect by conferring resistance to various types of stress and cell death, which may be applied in future bio‐artificial liver support systems and gene therapy for liver diseases 14 . Since Trx is a redox‐sensitive molecule, 15 serum Trx levels are believed to be a clinically useful marker for oxidative stress, and the ratio of expression of Trx and Trx binding protein 2, which is an endogenous inhibitor of Trx, could be a novel marker of liver diseases like NASH 16 . Sumida et al., 17 and Nakashima et al.…”