The thioredoxin antioxidant system - PubMed (original) (raw)

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The thioredoxin antioxidant system

Jun Lu et al. Free Radic Biol Med. 2014 Jan.

Abstract

The thioredoxin (Trx) system, which is composed of NADPH, thioredoxin reductase (TrxR), and thioredoxin, is a key antioxidant system in defense against oxidative stress through its disulfide reductase activity regulating protein dithiol/disulfide balance. The Trx system provides the electrons to thiol-dependent peroxidases (peroxiredoxins) to remove reactive oxygen and nitrogen species with a fast reaction rate. Trx antioxidant functions are also shown by involvement in DNA and protein repair by reducing ribonucleotide reductase, methionine sulfoxide reductases, and regulating the activity of many redox-sensitive transcription factors. Moreover, Trx systems play critical roles in the immune response, virus infection, and cell death via interaction with thioredoxin-interacting protein. In mammalian cells, the cytosolic and mitochondrial Trx systems, in which TrxRs are high molecular weight selenoenzymes, together with the glutathione-glutaredoxin (Grx) system (NADPH, glutathione reductase, GSH, and Grx) control the cellular redox environment. Recently mammalian thioredoxin and glutathione systems have been found to be able to provide the electrons crossly and to serve as a backup system for each other. In contrast, bacteria TrxRs are low molecular weight enzymes with a structure and reaction mechanism distinct from mammalian TrxR. Many bacterial species possess specific thiol-dependent antioxidant systems, and the significance of the Trx system in the defense against oxidative stress is different. Particularly, the absence of a GSH-Grx system in some pathogenic bacteria such as Helicobacter pylori, Mycobacterium tuberculosis, and Staphylococcus aureus makes the bacterial Trx system essential for survival under oxidative stress. This provides an opportunity to kill these bacteria by targeting the TrxR-Trx system.

Keywords: AhpC; AhpF; Alkyl hydroperoxide peroxidase subunit C; Alkyl hydroperoxide peroxidase subunit F; B. subtilis; BSO; Bacillus subtilis; Bacterioferritin comigratory protein; Bcp; Buthionine sulfoximine; Catalase; Dihydrolipoamide succinyltransferase; E. coli; E. faecalis; Entercoccus faecalis; Escherichia coli; FAD; Flavin adenine dinucleotide; GPx; GR; GSH; GST; Glutaredoxin; Glutathione; Glutathione peroxidise; Glutathione reductase; Glutathione transferase; Grx; H. pylori; HDAC; HTLV-1; Helicobacter pylori; Histone deacetylases; Human T-lymphotropic virus type I; KatA; KatG; Keap1; Kelch-like ECH-associated protein 1; M. tuberculosis; MSH; Methionine-O-sulfoxide reductase; Methionine-S-sulfoxide reductase; Mrx; MsrA; MsrB; Mtr; Mycobacterium tuberculosis; Mycoredoxin; Mycothione; Mycothione reductase; NADPH; Nicotinamide adenine dinucleotide phosphate; Nrf2; Nuclear factor erythroid-related factor 2; PDI; Peroxiredoxin; Protein disulfide isomerase; Prx; RNR; ROS; Ribonucleotide reductase; S. aureus; S. pyogenes; Sec; Staphylococcus aureus; Streptococcus pyogenes; SucB; TGR; TS(2); TXNIP; Thiol peroxidase; Thioredoxin; Thioredoxin glutathione reductase; Thioredoxin interacting protein; Thioredoxin reductase; Tpx; Trx; TrxR; TryR; Trypanothione; Trypanothione reductase; U, selenocysteine; WT; Wild type; antioxidant; catalase peroxidase; glutathione; peroxiredoxin; reactive oxygen species; thioredoxin.

Copyright © 2013 Elsevier Inc. All rights reserved.

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