ArticleThe Journal of biological chemistry2010
The selenium-independent inherent pro-oxidant NADPH oxidase activity of mammalian thioredoxin reductase and its selenium-dependent direct peroxidase activities.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Bicyclic Selenenyl Sulfides with Tuned Bioreductive Step Rates Reveal Constraints for Probes Targeting Thioredoxin Reductase.Angewandte Chemie (International ed. in English) · 2025Article
- Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- TXNRD1 drives the innate immune response in senescent cells with implications for age-associated inflammation.Nature aging · 2024Article
- Mercury accumulation and biomarkers of exposure in two popular recreational fishes in Hawaiian waters.Ecotoxicology (London, England) · 2023Article
- Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of Thioredoxin Reductase 1 in RAW 264.7 Cells.Molecules (Basel, Switzerland) · 2022Article
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- Article
- Piperlongumine Inhibits Thioredoxin Reductase 1 by Targeting Selenocysteine Residues and Sensitizes Cancer Cells to Erastin.Antioxidants (Basel, Switzerland) · 2022Article
- Oxidized Forms of Ergothioneine Are Substrates for Mammalian Thioredoxin Reductase.Antioxidants (Basel, Switzerland) · 2022Article
- Comprehensive chemical proteomics analyses reveal that the new TRi-1 and TRi-2 compounds are more specific thioredoxin reductase 1 inhibitors than auranofin.Redox biology · 2021Article
- Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry.Molecular neurobiology · 2021Review
- The interplay between oxidative stress and bioenergetic failure in neuropsychiatric illnesses: can we explain it and can we treat it?Molecular biology reports · 2020Review
- Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis.ACS infectious diseases · 2020Article
- Control of protein function through oxidation and reduction of persulfidated states.Science advances · 2020Article
- Manumycin A Is a Potent Inhibitor of Mammalian Thioredoxin Reductase-1 (TrxR-1).ACS medicinal chemistry letters · 2018Article
- Butaselen prevents hepatocarcinogenesis and progression through inhibiting thioredoxin reductase activity.Redox biology · 2018Article
- The A to Z of modulated cell patterning by mammalian thioredoxin reductases.Free radical biology & medicine · 2018Review
- Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium.Scientific reports · 2017Article
- Brevetoxin-2, is a unique inhibitor of the C-terminal redox center of mammalian thioredoxin reductase-1.Toxicology and applied pharmacology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Mammalian thioredoxin reductase (TrxR) is an NADPH-dependent homodimer with three redox-active centers per subunit: a FAD, an N-terminal domain dithiol (Cys(59)/Cys(64)), and a C-terminal cysteine/selenocysteine motif (Cys(497)/Sec(498)). TrxR has multiple roles in antioxidant defense. Opposing these functions, it may also assume a pro-oxidant role under some conditions. In the absence of its main electron-accepting substrates (e.g. thioredoxin), wild-type TrxR generates superoxide (O ), which was here detected and quantified by ESR spin trapping with 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). The peroxidase activity of wild-type TrxR efficiently converted the O adduct (DEPMPO/HOO(*)) to the hydroxyl radical adduct (DEPMPO/HO(*)). This peroxidase activity was Sec-dependent, although multiple mutants lacking Sec could still generate O . Variants of TrxR with C59S and/or C64S mutations displayed markedly reduced inherent NADPH oxidase activity, suggesting that the Cys(59)/Cys(64) dithiol is required for O generation and that O is not derived directly from the FAD. Mutations in the Cys(59)/Cys(64) dithiol also blocked the peroxidase and disulfide reductase activities presumably because of an inability to reduce the Cys(497)/Sec(498) active site. Although the bulk of the DEPMPO/HO(*) signal generated by wild-type TrxR was due to its combined NADPH oxidase and Sec-dependent peroxidase activities, additional experiments showed that some free HO(*) could be generated by the enzyme in an H(2)O(2)-dependent and Sec-independent manner. The direct NADPH oxidase and peroxidase activities of TrxR characterized here give insights into the full catalytic potential of this enzyme and may have biological consequences beyond those solely related to its reduction of thioredoxin.
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