{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:19:47Z","timestamp":1793049587979,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Severe acute pancreatitis (SAP) is an acute abdominal disease with extremely high mortality; autophagy\u2010dependent ferroptosis plays a crucial role in acute pancreatitis. However, the specific underlying mechanism remains unclear. To investigate the role of nuclear receptor coactivator 4 (NCOA4) in SAP and the mechanism by which tetrandrine influences it. Experimental SAP models were established using L\u2010arginine (L\u2010Arg) induction to observe changes in NCOA4 expression. Knockout and overexpression experiments of NCOA4 were conducted to assess the impact on SAP. Additionally, in\u00a0vitro cell experiments were performed to verify these findings. Furthermore, the impact of N\u2010glycosylation of NCOA4 on its function, particularly its binding ability with ferritin heavy chain 1 (FTH1), was studied. Finally, the effects of tetrandrine on N\u2010glycosylation of NCOA4, the binding between NCOA4 and FTH1, and the progression of SAP were analyzed. NCOA4 expression was significantly upregulated in SAP. Knockout of NCOA4 improved the phenotype of SAP, whereas its overexpression exacerbated SAP. This was also confirmed in\u00a0vitro. N\u2010glycosylation of NCOA4 is crucial for its binding with FTH1, which in turn affects ferroptosis. Tetrandrine targets the N\u2010glycosylation of NCOA4, weakening the interaction between NCOA4 and FTH1, thereby inhibiting the progression of SAP. This study demonstrates that tetrandrine targets the N\u2010glycosylation of NCOA4, inhibiting autophagy\u2010dependent ferroptosis mediated by its binding to FTH1 and thus ameliorates SAP. This finding provides us with a novel therapeutic approach for SAP and offers a new perspective on understanding the mechanism of action of tetrandrine in SAP.<\/jats:p>","DOI":"10.1096\/fj.202500404r","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T09:49:35Z","timestamp":1746524975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tetrandrine Improves Severe Acute Pancreatitis by Inhibiting\n                    <scp>NCOA4<\/scp>\n                    Glycosylation\u2010Mediated Binding to\n                    <scp>FTH1<\/scp>\n                    and Inducing Autophagy\u2010Dependent Ferroptosis"],"prefix":"10.1096","volume":"39","author":[{"given":"Sen","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[{"name":"Endocrinology Department Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junting","family":"Hu","sequence":"additional","affiliation":[{"name":"Neurosurgery Department Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6031-6268","authenticated-orcid":false,"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.20317"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.041"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.03.002"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2319901"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2170960"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2152209"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00294-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3982"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00850-0"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107133"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01188-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28062701"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107659"},{"key":"e_1_2_11_15_1","first-page":"1057","article-title":"Tetrandrine and Related Bis\u2010Benzylisoquinoline Alkaloids From Medicinal Herbs: Cardiovascular Effects and Mechanisms of Action","volume":"23","author":"Kwan C. 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