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The thioredoxin antioxidant system.
Free Radic Biol Med. 2014 Jan; 66:75-87.FR

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.

Authors+Show Affiliations

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: Jun.lu@ki.se.Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: Arne.Holmgren@ki.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23899494

Citation

Lu, Jun, and Arne Holmgren. "The Thioredoxin Antioxidant System." Free Radical Biology & Medicine, vol. 66, 2014, pp. 75-87.
Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radic Biol Med. 2014;66:75-87.
Lu, J., & Holmgren, A. (2014). The thioredoxin antioxidant system. Free Radical Biology & Medicine, 66, 75-87. https://doi.org/10.1016/j.freeradbiomed.2013.07.036
Lu J, Holmgren A. The Thioredoxin Antioxidant System. Free Radic Biol Med. 2014;66:75-87. PubMed PMID: 23899494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The thioredoxin antioxidant system. AU - Lu,Jun, AU - Holmgren,Arne, Y1 - 2013/07/27/ PY - 2013/02/28/received PY - 2013/07/22/revised PY - 2013/07/23/accepted PY - 2013/8/1/entrez PY - 2013/8/1/pubmed PY - 2014/8/15/medline KW - AhpC KW - AhpF KW - Alkyl hydroperoxide peroxidase subunit C KW - Alkyl hydroperoxide peroxidase subunit F KW - B. subtilis KW - BSO KW - Bacillus subtilis KW - Bacterioferritin comigratory protein KW - Bcp KW - Buthionine sulfoximine KW - Catalase KW - Dihydrolipoamide succinyltransferase KW - E. coli KW - E. faecalis KW - Entercoccus faecalis KW - Escherichia coli KW - FAD KW - Flavin adenine dinucleotide KW - GPx KW - GR KW - GSH KW - GST KW - Glutaredoxin KW - Glutathione KW - Glutathione peroxidise KW - Glutathione reductase KW - Glutathione transferase KW - Grx KW - H. pylori KW - HDAC KW - HTLV-1 KW - Helicobacter pylori KW - Histone deacetylases KW - Human T-lymphotropic virus type I KW - KatA KW - KatG KW - Keap1 KW - Kelch-like ECH-associated protein 1 KW - M. tuberculosis KW - MSH KW - Methionine-O-sulfoxide reductase KW - Methionine-S-sulfoxide reductase KW - Mrx KW - MsrA KW - MsrB KW - Mtr KW - Mycobacterium tuberculosis KW - Mycoredoxin KW - Mycothione KW - Mycothione reductase KW - NADPH KW - Nicotinamide adenine dinucleotide phosphate KW - Nrf2 KW - Nuclear factor erythroid-related factor 2 KW - PDI KW - Peroxiredoxin KW - Protein disulfide isomerase KW - Prx KW - RNR KW - ROS KW - Ribonucleotide reductase KW - S. aureus KW - S. pyogenes KW - Sec KW - Staphylococcus aureus KW - Streptococcus pyogenes KW - SucB KW - TGR KW - TS(2) KW - TXNIP KW - Thiol peroxidase KW - Thioredoxin KW - Thioredoxin glutathione reductase KW - Thioredoxin interacting protein KW - Thioredoxin reductase KW - Tpx KW - Trx KW - TrxR KW - TryR KW - Trypanothione KW - Trypanothione reductase KW - U, selenocysteine KW - WT KW - Wild type KW - antioxidant KW - catalase peroxidase KW - glutathione KW - peroxiredoxin KW - reactive oxygen species KW - thioredoxin SP - 75 EP - 87 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 66 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/23899494/The_thioredoxin_antioxidant_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(13)00380-8 DB - PRIME DP - Unbound Medicine ER -