ArticleThe Journal of biological chemistry2012
Glutathione and glutaredoxin act as a backup of human thioredoxin reductase 1 to reduce thioredoxin 1 preventing cell death by aurothioglucose.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 222 citations in OpenAlex.
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- Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency.Nature chemical biology · 2026Article
- Selenium in the Preterm Infant: Are We Supplementing Enough in This Vulnerable Population?Nutrients · 2026Review
- Intracellular enzymatic reducing systems control receptor tyrosine kinase signaling via PTP1B.Science advances · 2026Article
- Insights into the activation patterns of 1,2-dithiolane unit in biofunctional molecules.Nature communications · 2026Article
- Optimized Monothiol Thioredoxin Derivative (ORP100S) Protects In Vitro and In Vivo from Radiation and Chemotoxicity Without Promoting Tumor Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Computer-Aided Discovery of Natural Compounds Targeting the ADAR2 dsRBD2-RNA Interface and Computational Modeling of Full-Length ADAR2 Protein Structure.International journal of molecular sciences · 2025Article
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- Gold complex QB1561 suppresses drug-resistant cancer cells by inhibiting TrxR and mitochondrial respiratory function.Frontiers in pharmacology · 2025Article
- Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Disulfide stress and its role in cardiovascular diseases.Redox biology · 2024Review
- The significant role of amino acid metabolic reprogramming in cancer.Cell communication and signaling : CCS · 2024Review
- Protein vicinal thiols as intrinsic probes of brain redox states in health, aging, and ischemia.Metabolic brain disease · 2024Article
- Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Insights into the Multifaceted Roles of Thioredoxin-1 System: Exploring Knockout Murine Models.Biology · 2024Review
- Role of thioredoxin in chronic obstructive pulmonary disease (COPD): a promising future target.Respiratory research · 2023Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thioredoxin reductase 1 (TrxR1) in cytosol is the only known reductant of oxidized thioredoxin 1 (Trx1) in vivo so far. We and others found that aurothioglucose (ATG), a well known active-site inhibitor of TrxR1, inhibited TrxR1 activity in HeLa cell cytosol but had no effect on the viability of the cells. Using a redox Western blot analysis, no change was observed in redox state of Trx1, which was mainly fully reduced with five sulfhydryl groups. In contrast, auranofin killed cells and oxidized Trx1, also targeting mitochondrial TrxR2 and Trx2. Combining ATG with ebselen gave a strong synergistic effect, leading to Trx1 oxidation, reactive oxygen species accumulation, and cell death. We hypothesized that there should exist a backup system to reduce Trx1 when only TrxR1 activity was lost. Our results showed that physiological concentrations of glutathione, NADPH, and glutathione reductase reduced Trx1 in vitro and that the reaction was strongly stimulated by glutaredoxin1. Simultaneous depletion of TrxR activity by ATG and glutathione by buthionine sulfoximine led to overoxidation of Trx1 and loss of HeLa cell viability. In conclusion, the glutaredoxin system and glutathione have a backup role to keep Trx1 reduced in cells with loss of TrxR1 activity. Monitoring the redox state of Trx1 shows that cell death occurs when Trx1 is oxidized, followed by general protein oxidation catalyzed by the disulfide form of thioredoxin.
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