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Serum thioredoxin reductase levels increase in response to chemically induced acute liver injury
Authors:Kang Sun  Sofi E Eriksson  Yanping Tan  Le Zhang  Elias SJ Arnér  Jinsong Zhang
Institution:1. School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui, PR China;2. Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Abstract:

Background

Mammalian thioredoxin reductases (TrxR) are selenoproteins with important roles in antioxidant defense and redox regulation, principally linked to functions of their main substrates thioredoxins (Trx). All major forms of TrxR are intracellular while levels in serum are typically very low.

Methods

Serum TrxR levels were determined with immunoblotting using antibodies against mouse TrxR1 and total enzyme activity measurements were performed, with serum and tissue samples from mouse models of liver injury, as triggered by either thioacetamide (TAA) or carbon tetrachloride (CCl4).

Results

TrxR levels in serum increased upon treatment and correlated closely with those of alanine aminotransferase (ALT), an often used serum biomarker for liver damage. In contrast, Trx1, glutathione reductase, superoxide dismutase or selenium-containing glutathione peroxidase levels in serum displayed much lower increases than TrxR or ALT.

Conclusions

Serum TrxR levels are robustly elevated in mouse models of chemically induced liver injury.

General significance

The exaggerated TrxR release to serum upon liver injury may reflect more complex events than a mere passive release of hepatic enzymes to the extracellular milieu. It can also not be disregarded that enzymatically active TrxR in serum could have yet unidentified physiological functions.
Keywords:ALT  alanine aminotransferase  CCl4  carbon tetrachloride  DTNB  dithio-bis-nitrobenzoic acid  GPx  glutathione peroxidase  GR  glutathione reductase  i  p    intraperitoneally  Nrf2  nuclear factor erythroid 2-related factor 2  PBS  phosphate buffer saline  SOD  superoxide dismutase  TAA  thioacetamide  Trx  thioredoxin  TrxR  thioredoxin reductase
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