{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:48:55Z","timestamp":1792842535007,"version":"4.5.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:00:00Z","timestamp":1494892800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>Ferroptosis is a recently identified iron\u2010dependent form of nonapoptotic cell death implicated in brain, kidney, and heart pathology. However, the biological roles of iron and iron metabolism in ferroptosis remain poorly understood. Here, we studied the functional role of iron and iron metabolism in the pathogenesis of ferroptosis. We found that ferric citrate potently induces ferroptosis in murine primary hepatocytes and bone marrow\u2013derived macrophages. Next, we screened for ferroptosis in mice fed a high\u2010iron diet and in mouse models of hereditary hemochromatosis with iron overload. We found that ferroptosis occurred in mice fed a high\u2010iron diet and in two knockout mouse lines that develop severe iron overload (<jats:italic toggle=\"yes\">Hjv\u2013\/\u2013\n                           <\/jats:italic> and <jats:italic toggle=\"yes\">Smad4Alb\/Alb\n                           <\/jats:italic> mice) but not in a third line that develops only mild iron overload (<jats:italic toggle=\"yes\">Hfe<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice). Moreover, we found that iron overload\u2013induced liver damage was rescued by the ferroptosis inhibitor ferrostatin\u20101. To identify the genes involved in iron\u2010induced ferroptosis, we performed microarray analyses of iron\u2010treated bone marrow\u2013derived macrophages. Interestingly, solute carrier family 7, member 11 (<jats:italic toggle=\"yes\">Slc7a11<\/jats:italic>), a known ferroptosis\u2010related gene, was significantly up\u2010regulated in iron\u2010treated cells compared with untreated cells. However, genetically deleting <jats:italic toggle=\"yes\">Slc7a11<\/jats:italic> expression was not sufficient to induce ferroptosis in mice. Next, we studied iron\u2010treated hepatocytes and bone marrow\u2013derived macrophages isolated from <jats:italic toggle=\"yes\">Slc7a11\u2013\/\u2013\n                           <\/jats:italic> mice fed a high\u2010iron diet. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> We found that iron treatment induced ferroptosis in <jats:italic toggle=\"yes\">Slc7a11\u2013\/\u2013\n                           <\/jats:italic> cells, indicating that deleting <jats:italic toggle=\"yes\">Slc7a11<\/jats:italic> facilitates the onset of ferroptosis specifically under high\u2010iron conditions; these results provide compelling evidence that iron plays a key role in triggering Slc7a11\u2010mediated ferroptosis and suggest that ferroptosis may be a promising target for treating hemochromatosis\u2010related tissue damage. (H<jats:sc>epatology<\/jats:sc> 2017;66:449\u2013465).<\/jats:p>","DOI":"10.1002\/hep.29117","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T12:28:54Z","timestamp":1486988934000},"page":"449-465","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":627,"title":["Characterization of ferroptosis in murine models of hemochromatosis"],"prefix":"10.1097","volume":"66","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"An","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjun","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexian","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoli","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Program in Molecular and Cell Biology, School of Medicine,Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxia","family":"Min","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fudi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhengzhou University; School of Public Health, The First Affiliated Hospital, Institute of Translational Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,School of Medicine, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,5,16]]},"reference":[{"key":"hep29117-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1152\/physrev.00008.2013","article-title":"Systemic iron homeostasis","volume":"93","year":"2013","journal-title":"Physiol 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Cell"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.29117","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201708000-00016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:03:38Z","timestamp":1729209818000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201708000-00016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,16]]},"references-count":47,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.29117","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,16]]},"assertion":[{"value":"2016-11-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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