ArticleMetallomics : integrated biometal science2023
Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione.
Article in Metallomics : integrated biometal science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Integrated Multi-Endpoint Analysis of Soluble Copper(II) Chloride-Induced Oxidative Stress, Mitochondrial Dysfunction, and Genotoxicity in RAW264.7 Macrophages.Biological trace element research · 2026Article
- Investigation on the Cytotoxicity of Hydroxycinnamic and Hydroxybenzoic Acid-Based Natural Antioxidant Conjugated Terpyridine Analogues toward Triple-Negative Breast Cancer.ACS medicinal chemistry letters · 2026Article
- Antioxidant Supplementation ReducesCurrent developments in nutrition · 2026Article
- High copper levels induce oxidative stress and inflammatory processes in a cell culture model of Wilson's disease.Molecular and cellular biochemistry · 2026Article
- Antioxidant Potential ofMolecules (Basel, Switzerland) · 2026Article
- Copper ionophore elicits calpain-dependent paraptosis coincident with proteotoxic stress.Cell communication and signaling : CCS · 2025Article
- Trace element-linked DNA methylation sites and their association with type 2 diabetes and cardiovascular diseases: EPIC-Potsdam cohort study.Clinical epigenetics · 2025Article
- IsotopicBiomolecules · 2025Article
- [Progress on the research of hepatolenticular degeneration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Copper-Induced Stimulation of Ectophosphatase Activity ofPathogens (Basel, Switzerland) · 2025Article
- Feasibility of controlled nitric oxide generationDalton transactions (Cambridge, England : 2003) · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- When Metal Complexes Evolve, and a Minor Species is the Most Active: the Case of Bis(Phenanthroline)Copper in the Catalysis of Glutathione Oxidation and Hydroxyl Radical Generation.Angewandte Chemie (International ed. in English) · 2025Article
- Understanding the relationship between cuproptosis and the development of hepatocellular carcinoma: implications for targeted therapies.Frontiers in immunology · 2025Review
- Leptospira interrogans biofilm transcriptome highlights adaption to starvation and general stress while maintaining virulence.NPJ biofilms and microbiomes · 2024Article
- Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies.International journal of molecular sciences · 2024Review
- Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review.Journal of cancer research and clinical oncology · 2024Review
- Multiple Physiological and Biochemical Functions of Ascorbic Acid in Plant Growth, Development, and Abiotic Stress Response.International journal of molecular sciences · 2024Review
- Exploring the Antioxidant Potential ofNutrients · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Copper (Cu) is essential for most organisms, but it can be poisonous in excess, through mechanisms such as protein aggregation, trans-metallation, and oxidative stress. The latter could implicate the formation of potentially harmful reactive oxygen species (O2•-, H2O2, and HO•) via the redox cycling between Cu(II)/Cu(I) states in the presence of dioxygen and physiological reducing agents such as ascorbate (AscH), cysteine (Cys), and the tripeptide glutathione (GSH). Although the reactivity of Cu with these reductants has been previously investigated, the reactions taking place in a more physiologically relevant mixture of these biomolecules are not known. Hence, we report here on the reactivity of Cu with binary and ternary mixtures of AscH, Cys, and GSH. By measuring AscH and thiol oxidation, as well as HO• formation, we show that Cu reacts preferentially with GSH and Cys, halting AscH oxidation and also HO• release. This could be explained by the formation of Cu-thiolate clusters with both GSH and, as we first demonstrate here, Cys. Moreover, we observed a remarkable acceleration of Cu-catalyzed GSH oxidation in the presence of Cys. We provide evidence that both thiol-disulfide exchange and the generated H2O2 contribute to this effect. Based on these findings, we speculate that Cu-induced oxidative stress may be mainly driven by GSH depletion and/or protein disulfide formation rather than by HO• and envision a synergistic effect of Cys on Cu toxicity.
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