{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:49:08Z","timestamp":1773888548038,"version":"3.50.1"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Trace Elements in Medicine and Biology"],"published-print":{"date-parts":[[2026,4]]},"DOI":"10.1016\/j.jtemb.2026.127854","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T17:21:37Z","timestamp":1772558497000},"page":"127854","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Exposure to copper induces oxidative stress and apoptosis in human MEG-01 cells"],"prefix":"10.1016","volume":"94","author":[{"given":"Zhanqin","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meidie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtemb.2026.127854_bib1","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0753-3322(03)00012-X","article-title":"Trace elements in human physiology and pathology","volume":"57","author":"Tapiero","year":"2003","journal-title":"Copper Biomed. Pharmacother."},{"issue":"11","key":"10.1016\/j.jtemb.2026.127854_bib2","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1016\/j.spinee.2024.06.018","article-title":"Copper deficiency myelopathy mimicking cervical spondylitic myelopathy: a systematic review of the literature with case report","volume":"24","author":"Chen","year":"2024","journal-title":"Spine J."},{"issue":"11","key":"10.1016\/j.jtemb.2026.127854_bib3","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/17474086.2022.2142113","article-title":"Copper deficiency, a rare but correctable cause of pancytopenia: a review of literature","volume":"15","author":"Tahir","year":"2022","journal-title":"Expert Rev. Hematol."},{"key":"10.1016\/j.jtemb.2026.127854_bib4","article-title":"Copper in human health and disease: insights from inherited disorders","volume":"10","author":"Petruzzelli","year":"2025","journal-title":"Physiology"},{"key":"10.1016\/j.jtemb.2026.127854_bib5","doi-asserted-by":"crossref","first-page":"81923","DOI":"10.1007\/s11356-022-21521-2","article-title":"Hepatic and renal toxicity following the injection of copper oxide nanoparticles (CuO NPs) in mature male Westar rats: histochemical and caspase 3 immunohistochemical reactivities","volume":"29","author":"Ghonimi","year":"2022","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"10.1016\/j.jtemb.2026.127854_bib6","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/toxres\/tfad011","article-title":"Evaluation of oxidative stress-mediated cytotoxicity and genotoxicity of copper and flubendiamide: amelioration by antioxidants in vivo and in vitro","volume":"12","author":"Mandil","year":"2023","journal-title":"Toxicol. Res."},{"key":"10.1016\/j.jtemb.2026.127854_bib7","article-title":"Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1\/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis","volume":"26","author":"Li","year":"2023","journal-title":"iScience"},{"key":"10.1016\/j.jtemb.2026.127854_bib8","doi-asserted-by":"crossref","DOI":"10.3390\/toxics13010063","article-title":"The role of autophagy in copper-induced apoptosis and developmental neurotoxicity in SH-SY5Y Cells","volume":"13","author":"Lu","year":"2025","journal-title":"Toxics"},{"key":"10.1016\/j.jtemb.2026.127854_bib9","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12920-024-01960-1","article-title":"Macrothrombocytopenia with leukocyte inclusions in a patient with Wilson disease: a case report and literature review","volume":"17","author":"Lin","year":"2024","journal-title":"BMC Med. Genom."},{"key":"10.1016\/j.jtemb.2026.127854_bib10","first-page":"61","article-title":"Wilson disease with thrombocytopenia (case report)","author":"Zhvania","year":"2014","journal-title":"Georgian Med. N."},{"key":"10.1016\/j.jtemb.2026.127854_bib11","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.revmed.2016.08.010","article-title":"[Ecchymosis as the presenting manifestation of Wilson disease: a case report]","volume":"38","author":"Bayer","year":"2017","journal-title":"Rev. Med. Interne"},{"key":"10.1016\/j.jtemb.2026.127854_bib12","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s12881-020-01062-6","article-title":"Genotype-phenotype variable correlation in Wilson disease: clinical history of two sisters with the similar genotype","volume":"21","author":"Sapuppo","year":"2020","journal-title":"BMC Med. Genet."},{"issue":"4","key":"10.1016\/j.jtemb.2026.127854_bib13","article-title":"An unusual presentation of Wilson's disease","volume":"16","author":"Kanitkar","year":"2024","journal-title":"Cureus"},{"issue":"10","key":"10.1016\/j.jtemb.2026.127854_bib14","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.7150\/ijms.44338","article-title":"Cirrhosis in Wilson disease is characterized by impaired hepatic synthesis, leukopenia and thrombocytopenia","volume":"17","author":"Zhong","year":"2020","journal-title":"Int. J. Med. Sci."},{"issue":"3-4","key":"10.1016\/j.jtemb.2026.127854_bib15","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1159\/000355276","article-title":"Worsening of Wilson disease following penicillamine therapy","volume":"71","author":"Kalita","year":"2014","journal-title":"Eur. Neurol."},{"issue":"14","key":"10.1016\/j.jtemb.2026.127854_bib16","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.3390\/diagnostics13142424","article-title":"Copper deficiency as Wilson's disease overtreatment: a systematic review","volume":"13","author":"Litwin","year":"2023","journal-title":"Diagnostics"},{"issue":"8","key":"10.1016\/j.jtemb.2026.127854_bib17","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S0025-6196(25)38111-5","article-title":"Hematologic (cytopenic) manifestations of Wilson's disease (hepatolenticular degeneration)","volume":"53","author":"Hogland","year":"1978","journal-title":"Mayo Clin. Proc."},{"key":"10.1016\/j.jtemb.2026.127854_bib18","doi-asserted-by":"crossref","first-page":"16867","DOI":"10.18632\/aging.103585","article-title":"Oxidative stress, apoptosis and inflammatory responses involved in copper-induced pulmonary toxicity in mice","volume":"12","author":"Jian","year":"2020","journal-title":"Aging"},{"key":"10.1016\/j.jtemb.2026.127854_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2025.117783","article-title":"Copper excess induces autophagy dysfunction and mitochondrial ROS-ferroptosis progression, inhibits cellular biosynthesis of milk protein and lipid in bovine mammary epithelial cells","volume":"291","author":"Fan","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.jtemb.2026.127854_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2020.111730","article-title":"Mechanism of CuSO4 cytotoxicity in goat erythrocytes after high-level in vitro exposure to isotonic media","volume":"208","author":"Tao","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.jtemb.2026.127854_bib21","first-page":"315","article-title":"Genotoxicity of aluminium oxide, iron oxide, and copper nanoparticles in mouse bone marrow cells","volume":"72","author":"Sadiq","year":"2021","journal-title":"Arh. Hig. Rada. Toksikol."},{"key":"10.1016\/j.jtemb.2026.127854_bib22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12989-016-0169-x","article-title":"Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles","volume":"13","author":"Lee","year":"2016","journal-title":"Part. Fibre Toxicol."},{"key":"10.1016\/j.jtemb.2026.127854_bib23","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/17435390.2018.1530390","article-title":"Toxicity of copper oxide and basic copper carbonate nanoparticles after short-term oral exposure in rats","volume":"13","author":"De Jong","year":"2019","journal-title":"Nanotoxicology"},{"issue":"1","key":"10.1016\/j.jtemb.2026.127854_bib24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0014-4827(91)90560-H","article-title":"Production of platelet-like particles by a human megakaryoblastic leukemia cell line (MEG-01)","volume":"193","author":"Takeuchi","year":"1991","journal-title":"Exp. Cell Res."},{"issue":"6586","key":"10.1016\/j.jtemb.2026.127854_bib25","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.jtemb.2026.127854_bib26","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41392-022-01229-y","article-title":"Copper homeostasis and cuproptosis in health and disease","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"10.1016\/j.jtemb.2026.127854_bib27","doi-asserted-by":"crossref","first-page":"5042","DOI":"10.1007\/s12011-022-03107-8","article-title":"Copper oxide nanoparticles exhibit cell death through oxidative stress responses in human airway epithelial cells: a mechanistic study","volume":"200","author":"Farshori","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"issue":"20","key":"10.1016\/j.jtemb.2026.127854_bib28","doi-asserted-by":"crossref","first-page":"9457","DOI":"10.1039\/D5CS00544B","article-title":"Mechanism of oxidative stress and neurotoxicity associated with heme and copper-A\u03b2 relevant to Alzheimer's disease","volume":"54","author":"Dey","year":"2025","journal-title":"Chem. Soc. Rev."},{"issue":"6","key":"10.1016\/j.jtemb.2026.127854_bib29","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s10534-025-00728-z","article-title":"Copper and vanadium induce oxidative stress and pyroptosis in the duck brain via activating the TLR4\/NF-\u03baB-p65 signaling pathway","volume":"38","author":"Chen","year":"2025","journal-title":"Biometals"},{"issue":"2","key":"10.1016\/j.jtemb.2026.127854_bib30","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00204-024-03921-0","article-title":"Cellular mechanisms of copper neurotoxicity in human, differentiated neurons","volume":"99","author":"Witt","year":"2025","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.jtemb.2026.127854_bib31","article-title":"Repurposing melatonin's therapeutic potential in Wilson disease: addressing copper overload and redox imbalance","volume":"89","author":"Pandey","year":"2025","journal-title":"Redox Biol."},{"issue":"6","key":"10.1016\/j.jtemb.2026.127854_bib32","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202403002R","article-title":"Spermidine alleviates copper-induced oxidative stress, inflammation and cuproptosis in the liver","volume":"39","author":"Wang","year":"2025","journal-title":"FASEB J."},{"key":"10.1016\/j.jtemb.2026.127854_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2025.110779","article-title":"Melatonin ameliorates copper accumulation-induced cognitive impairment in Wilson disease via activation of the SIRT3\/FOXO3\u03b1 signaling pathway","volume":"284","author":"Wang","year":"2026","journal-title":"Neuropharmacology"},{"issue":"21","key":"10.1016\/j.jtemb.2026.127854_bib34","doi-asserted-by":"crossref","first-page":"15580","DOI":"10.3390\/ijms242115580","article-title":"Effects of copper or zinc organometallics on cytotoxicity, DNA damage and epigenetic changes in the HC-04 human liver cell line","volume":"24","author":"Desaulniers","year":"2023","journal-title":"Int J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.jtemb.2026.127854_bib35","doi-asserted-by":"crossref","DOI":"10.1093\/mtomcs\/mfad040","article-title":"Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione","volume":"15","author":"Falcone","year":"2023","journal-title":"Metallomics"},{"key":"10.1016\/j.jtemb.2026.127854_bib36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s44371-025-00275-z","article-title":"Reactive oxygen species (ROS): sources, generation, disease pathophysiology, and antioxidants","volume":"2","author":"Ansari","year":"2025","journal-title":"Discov. Chem."},{"issue":"8","key":"10.1016\/j.jtemb.2026.127854_bib37","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.3390\/biom15081130","article-title":"Therapeutic Applications and Mechanisms of Superoxide Dismutase (SOD) in Different Pathogenesis","volume":"15","author":"Anwar","year":"2025","journal-title":"Biomolecules"},{"key":"10.1016\/j.jtemb.2026.127854_bib38","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00775-021-01908-1","article-title":"Nitric oxide, chronic iron and copper overloads and regulation of redox homeostasis in rat liver","volume":"27","author":"Lairion","year":"2022","journal-title":"J. Biol. Inorg. Chem."},{"issue":"1","key":"10.1016\/j.jtemb.2026.127854_bib39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/sj.cdd.4402060","article-title":"Caspase function in programmed cell death","volume":"14","author":"Kumar","year":"2007","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.jtemb.2026.127854_bib40","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.cbpc.2016.03.010","article-title":"Copper induced apoptosis in Caco-2 and Hep-G2 cells: Expression of caspases 3, 8 and 9, AIF and p53","volume":"185-186","author":"Santos","year":"2016","journal-title":"Comp. Biochem. Physiol. C. Toxicol. Pharmacol."},{"key":"10.1016\/j.jtemb.2026.127854_bib41","article-title":"Copper induces oxidative stress and apoptosis in the mouse liver","volume":"2020","author":"Liu","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.jtemb.2026.127854_bib42","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26185591","article-title":"Curcumin and nano-curcumin mitigate copper neurotoxicity by modulating oxidative stress, inflammation, and Akt\/GSK-3beta signaling","volume":"26","author":"Sarawi","year":"2021","journal-title":"Molecules"},{"issue":"4","key":"10.1016\/j.jtemb.2026.127854_bib43","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00018-015-2087-8","article-title":"Mitophagy programs: mechanisms and physiological implications of mitochondrial targeting by autophagy","volume":"73","author":"Hamacher-Brady","year":"2016","journal-title":"Cell Mol. Life Sci."},{"issue":"6","key":"10.1016\/j.jtemb.2026.127854_bib44","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adj8027","article-title":"Three-step docking by WIPI2, ATG16L1, and ATG3 delivers LC3 to the phagophore","volume":"10","author":"Rao","year":"2024","journal-title":"Sci. Adv."},{"issue":"3","key":"10.1016\/j.jtemb.2026.127854_bib45","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4161\/auto.7.3.14487","article-title":"Selective autophagy mediated by autophagic adapter proteins","volume":"7","author":"Johansen","year":"2011","journal-title":"Autophagy"},{"issue":"6","key":"10.1016\/j.jtemb.2026.127854_bib46","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1080\/15548627.2023.2297623","article-title":"S-acylation regulates SQSTM1\/p62-mediated selective autophagy","volume":"20","author":"Huang","year":"2024","journal-title":"Autophagy"},{"issue":"11","key":"10.1016\/j.jtemb.2026.127854_bib47","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.3390\/cells10113118","article-title":"Direct interaction of ATP7B and LC3B proteins suggests a cooperative role of copper transportation and autophagy","volume":"10","author":"Pantoom","year":"2021","journal-title":"Cells"},{"issue":"1","key":"10.1016\/j.jtemb.2026.127854_bib48","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41420-023-01641-5","article-title":"ATP7B R778L mutant hepatocytes resist copper toxicity by activating autophagy and inhibiting necroptosis","volume":"9","author":"Tang","year":"2023","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.jtemb.2026.127854_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2019.104639","article-title":"Copper-induced apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction in male germ cells","volume":"61","author":"Kang","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.jtemb.2026.127854_bib50","doi-asserted-by":"crossref","DOI":"10.1590\/1414-431x2022e12252","article-title":"Nanosized copper particles induced mesangial cell toxicity via the autophagy pathway","volume":"55","author":"Xu","year":"2022","journal-title":"Braz. J. Med. Biol. Res."},{"issue":"1","key":"10.1016\/j.jtemb.2026.127854_bib51","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/toxics13010063","article-title":"The role of autophagy in copper-induced apoptosis and developmental neurotoxicity in SH-SY5Y cells","volume":"13","author":"Lu","year":"2025","journal-title":"Toxics"}],"container-title":["Journal of Trace Elements in Medicine and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0946672X26000404?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0946672X26000404?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:30:16Z","timestamp":1773873016000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0946672X26000404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":51,"alternative-id":["S0946672X26000404"],"URL":"https:\/\/doi.org\/10.1016\/j.jtemb.2026.127854","relation":{},"ISSN":["0946-672X"],"issn-type":[{"value":"0946-672X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exposure to copper induces oxidative stress and apoptosis in human MEG-01 cells","name":"articletitle","label":"Article Title"},{"value":"Journal of Trace Elements in Medicine and Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtemb.2026.127854","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"127854"}}