ArticleFree radical biology & medicine2009
Novel mechanism for regulation of extracellular SOD transcription and activity by copper: role of antioxidant-1.
Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Superoxide Dismutase Administration: A Review of Proposed Human Uses.Molecules (Basel, Switzerland) · 2021Pooled it
- Sprayable nanozyme hydrogel epigenetically remodels inflammation for diabetic wound regeneration.Nature communications · 2026Article
- Antioxidant System Response ofInternational journal of molecular sciences · 2025Article
- Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.Metallomics : integrated biometal science · 2024Review
- Molecular mechanisms and therapeutic strategies for ferroptosis and cuproptosis in ischemic stroke.Brain, behavior, & immunity - health · 2024Review
- Exploration of SOD3 from gene to therapeutic prospects: a brief review.Molecular biology reports · 2024Review
- Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Gene expression variation underlying tissue-specific responses to copper stress inbioRxiv : the preprint server for biology · 2023Article
- Ramifications of Heat Stress on Rabbit Production and Role of Nutraceuticals in Alleviating Its Negative Impacts: An Updated Review.Antioxidants (Basel, Switzerland) · 2023Review
- Oral Administration of Copper Chloride Damages DNA, Lowers Antioxidant Defense, Alters Metabolic Status, and Inhibits Membrane Bound Enzymes in Rat Kidney.Biological trace element research · 2023Article
- Copper chaperone antioxidant 1: multiple roles and a potential therapeutic target.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Brain copper may protect from cognitive decline and Alzheimer's disease pathology: a community-based study.Molecular psychiatry · 2022Article
- Article
- Superoxide Radicals in the Execution of Cell Death.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Copper chloride inhibits brush border membrane enzymes, alters antioxidant and metabolic status and damages DNA in rat intestine: a dose-dependent study.Environmental science and pollution research international · 2021Article
- Impact of EcSOD Perturbations in Cancer Progression.Antioxidants (Basel, Switzerland) · 2021Review
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Extracellular superoxide dismutase (SOD3), a secretory copper-containing antioxidant enzyme, plays an important role in various oxidative stress-dependent cardiovascular diseases. Although cofactor copper is required for SOD3 activity, it remains unknown whether it can regulate SOD3 transcription. We previously demonstrated that SOD3 activity requires the copper chaperone antioxidant-1 (Atox1), involved in copper delivery to SOD3 at the trans-Golgi network (TGN). Here we show that copper treatment in mouse fibroblasts significantly increases mRNA and protein levels of SOD3, but not SOD1, which is abolished in Atox1-deficient cells. Copper promotes Atox1 translocation to the nucleus. Promoter deletion analysis identifies copper- and Atox1-response elements (REs) at the SOD3 promoter. Gel-shift and ChIP assays reveal that Atox1 directly binds to the Atox1 RE in a copper-dependent manner in vitro and in vivo. Adenovirus-mediated reexpression in Atox1(-/-) cells of nucleus-targeted Atox1 (Atox1-NLS), but not TGN-targeted Atox1 (Atox1-TGN), increases SOD3 transcription without affecting SOD3 activity. Importantly, reexpression of both Atox1-NLS and Atox1-TGN together, but not either alone, in Atox1(-/-) cells increases SOD3 activity. SOD3 transcription is positively regulated by copper through the transcription factor function of Atox1, whereas the full activity of SOD3 requires both the copper chaperone and the transcription factor functions of Atox1. Thus, Atox1 is a potential therapeutic target for oxidant stress-dependent cardiovascular disease.
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Registered trials
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.