ArticleAntioxidants & redox signaling2014
Glutaredoxin 2 reduces both thioredoxin 2 and thioredoxin 1 and protects cells from apoptosis induced by auranofin and 4-hydroxynonenal.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 80 citations in OpenAlex.
- ASO Author Reflections: Glutaredoxin 2 has Potential as a Therapeutic Target for Colon Cancer.Annals of surgical oncology · 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
- Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies.International journal of molecular sciences · 2025Review
- Article
- Glutaredoxin2 reduces age-associated B cell differentiation through maintaining redox homeostasis.Frontiers in pharmacology · 2025Article
- Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients.International journal of molecular sciences · 2024Article
- Unresolved questions regarding cellular cysteine sources and their possible relationships to ferroptosis.Advances in cancer research · 2024Review
- Fluorescent Probes for Mammalian Thioredoxin Reductase: Mechanistic Analysis, Construction Strategies, and Future Perspectives.Biosensors · 2023Review
- Biological and Catalytic Properties of Selenoproteins.International journal of molecular sciences · 2023Review
- Evolutionarily Conserved Role of Thioredoxin Systems in Determining Longevity.Antioxidants (Basel, Switzerland) · 2023Review
- Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases.Translational neurodegeneration · 2023Review
- MitochondrialAntioxidants (Basel, Switzerland) · 2022Article
- Antioxidant Activities and Selenogene Transcription in the European Sea Bass (Dicentrarchus labrax) Liver Depend, in a Non-linear Manner, on the Se/Hg Molar Ratio of the Feeds.Biological trace element research · 2022Article
- Transcriptional changes of proteins of the thioredoxin and glutathione systems in Acanthamoeba spp. under oxidative stress - an RNA approach.Parasite (Paris, France) · 2022Article
- Glutaredoxin: Discovery, redox defense and much more.Redox biology · 2021Review
- Investigating the Thioredoxin and Glutathione Systems' Response in Lymphoma Cells after Treatment with [Au(d2pype)2]CL.Antioxidants (Basel, Switzerland) · 2021Article
- Thioredoxin and Glutaredoxin Systems as Potential Targets for the Development of New Treatments in Friedreich's Ataxia.Antioxidants (Basel, Switzerland) · 2020Review
- Enhanced thioredoxin, glutathione and Nrf2 antioxidant systems by safflower extract and aceglutamide attenuate cerebral ischaemia/reperfusion injury.Journal of cellular and molecular medicine · 2020Article
- TRIAP1 knockdown sensitizes non-small cell lung cancer to ionizing radiation by disrupting redox homeostasis.Thoracic cancer · 2020Article
- Sexual dimorphism in glutathione metabolism and glutathione-dependent responses.Redox biology · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMitochondrial thioredoxin (Trx) is critical for defense against oxidative stress-induced cell apoptosis. To date, mitochondrial thioredoxin reductase (TrxR) is the only known enzyme catalyzing Trx2 reduction in mitochondria. However, TrxR is sensitive to inactivation by exo/endogenous electrophiles, for example, 4-hydroxynonenal (HNE). In this study, we characterized the mitochondrial glutaredoxin 2 (Grx2) system as a backup for the mitochondrial TrxR. Meanwhile, as Grx2 is also present in the cytosol/nucleus of certain cancer cell lines, the reducing activity of Grx2 on Trx1 was also tested.
resultsGlutathione alone could reduce oxidized Trx2, and the presence of physiological concentrations of Grx2 markedly increased the reaction rate. HeLa cells with Grx2 overexpression (particularly in the mitochondria) exhibited higher viabilities than the wild-type cells after treatment with TrxR inhibitors (Auranofin or HNE), whereas knockdown of Grx2 sensitized the cells to TrxR inhibitors. Accordingly, Grx2 overexpression in the mitochondria had protected Trx2 from oxidation by HNE treatment, whereas Grx2 knockdown had sensitized Trx2 to oxidation. On the other hand, Grx2 reduced Trx1 with similar activities as that of Trx2. Overexpression of Grx2 in the cytosol had protected Trx1 from oxidation, indicating a supportive role of Grx2 in the cytosolic redox balance of cancer cells. INNOVATION: This work explores the reductase activity of Grx2 on Trx2/1, and demonstrates the physiological importance of the activity by using in vivo redox western blot assays.
conclusionGrx2 system could help to keep Trx2/1 reduced during an oxidative stress, thereby contributing to the anti-apoptotic signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.