{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:37:31Z","timestamp":1787225851853,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970556"],"award-info":[{"award-number":["81970556"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8217031247"],"award-info":[{"award-number":["8217031247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200716"],"award-info":[{"award-number":["82200716"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Acute pancreatitis (AP) is associated with acinar cell death and inflammatory responses. Ferroptosis is characterized by an overwhelming lipid peroxidation downstream of metabolic dysfunction, in which NADPH\u2010related redox systems have been recognized as the mainstay in ferroptosis control. Nevertheless, it remains unknown how ferroptosis is regulated in AP and whether we can target it to restrict AP development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Metabolomics were applied to explore changes in metabolic pathways in pancreatic acinar cells (PACs) in AP. Using wild\u2010type and Ptf1a<jats:sup>CreERT2\/+<\/jats:sup>IDH2<jats:sup>fl\/fl<\/jats:sup> mice, AP was induced by caerulein and sodium taurocholate (NaT). IDH2 overexpressing adenovirus was constructed for infection of PACs. Mice or PACs were pretreated with inhibitors of FSP1 or glutathione reductase. Pancreatitis severity, acinar cell injury, mitochondrial morphological changes and pancreatic lipid peroxidation were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Unsaturated fatty acid biosynthesis and the tricarboxylic acid cycle pathways were significantly altered in PACs during AP. Inhibition of ferroptosis reduced mitochondrial damage, lipid peroxidation and the severity of AP. During AP, the NADPH abundance and IDH2 expression were decreased. Acinar cell\u2010specific deletion of IDH2 exacerbated acinar cell ferroptosis and pancreatic injury. Pharmacological inhibition of NADPH\u2010dependent GSH\/GPX4 and FSP1\/CoQ<jats:sub>10<\/jats:sub> pathways abolished the protective effect of IDH2 overexpression on ferroptosis in acinar cells. CoQ<jats:sub>10<\/jats:sub> supplementation attenuated experimental pancreatitis via inhibiting acinar cell ferroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We identified the IDH2\u2010NADPH pathway as a novel regulator in protecting against AP via restricting acinar cell ferroptosis. Targeting the pathway and its downstream may shed light on AP treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16469","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T19:35:23Z","timestamp":1722108923000},"page":"4067-4084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["IDH2\u2010NADPH pathway protects against acute pancreatitis via suppressing acinar cell ferroptosis"],"prefix":"10.1111","volume":"181","author":[{"given":"Qi","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengli","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingpiao","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-9083","authenticated-orcid":false,"given":"Jianbo","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-6127","authenticated-orcid":false,"given":"Guoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital  Shanghai China"},{"name":"Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.12539"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1705-2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.10.012"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.054"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210518"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20154-8"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw013"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0181-1"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1707-0"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.07.009"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202205436"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3064"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.041"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32409"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.09.003"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016030349"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.215178"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304058"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06546-y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.02.093"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0158-2"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165971"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000002096"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.09.008"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06225-2"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.20317"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5818479"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12676"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.243"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20061638"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.054"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2015.11.016"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106900"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.021"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00441-1"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw4543"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.02.027"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-015-1192-3"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.015"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2006.105833"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-016-0406-x"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.002"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.011"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111847"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T15:19:07Z","timestamp":1728487147000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,27]]},"references-count":50,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/bph.16469"],"URL":"https:\/\/doi.org\/10.1111\/bph.16469","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,27]]},"assertion":[{"value":"2023-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}