{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:20:46Z","timestamp":1790835646611,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T00:00:00Z","timestamp":1687564800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["CHAPCOP-ANR-19-CE44-0018"],"award-info":[{"award-number":["CHAPCOP-ANR-19-CE44-0018"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2022\u2212, H2O2, and HO\u2022) 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\u2022 formation, we show that Cu reacts preferentially with GSH and Cys, halting AscH oxidation and also HO\u2022 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\u2022 and envision a synergistic effect of Cys on Cu toxicity.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfad040","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T05:11:46Z","timestamp":1687583506000},"source":"Crossref","is-referenced-by-count":43,"title":["Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1944-3552","authenticated-orcid":false,"given":"Enrico","family":"Falcone","sequence":"first","affiliation":[{"name":"Institut de Chimie (UMR 7177), University of Strasbourg\u2014CNRS , 4 Rue Blaise Pascal, 67081 Strasbourg , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Stellato","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Roma Tor Vergata , Via della Ricerca Scientifica 1\u201400133 Roma , Italy"},{"name":"INFN, Sezione di Roma Tor Vergata , Via della Ricerca Scientifica 1\u201400133 Roma , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Vileno","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177), University of Strasbourg\u2014CNRS , 4 Rue Blaise Pascal, 67081 Strasbourg , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merwan","family":"Bouraguba","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177), University of Strasbourg\u2014CNRS , 4 Rue Blaise Pascal, 67081 Strasbourg , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Lebrun","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177), University of Strasbourg\u2014CNRS , 4 Rue Blaise Pascal, 67081 Strasbourg , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Ilbert","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9 , CNRS, BIP, UMR 7281, IMM, 31 Chemin Aiguier, 13009 Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Morante","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Roma Tor Vergata , Via della Ricerca Scientifica 1\u2014 00133 Roma , Italy"},{"name":"INFN, Sezione di Roma Tor Vergata , Via della Ricerca Scientifica 1\u2014 00133 Roma , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-0806","authenticated-orcid":false,"given":"Peter","family":"Faller","sequence":"additional","affiliation":[{"name":"Institut de Chimie (UMR 7177), University of Strasbourg\u2014CNRS , 4 Rue Blaise Pascal, 67081 Strasbourg , France"},{"name":"Institut Universitaire de France (IUF) , 1 rue Descartes, 75231 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"issue":"21","key":"2023071009405707500_bib1","doi-asserted-by":"crossref","first-page":"R877","DOI":"10.1016\/j.cub.2011.09.040","article-title":"Copper: An essential metal in biology","volume":"21","author":"Festa","year":"2011","journal-title":"Curr. 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