{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:31:05Z","timestamp":1788337865233,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":166,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["BX20200154"],"award-info":[{"award-number":["BX20200154"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFC1604900"],"award-info":[{"award-number":["2019YFC1604900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100372"],"award-info":[{"award-number":["82100372"]}],"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":["82192911"],"award-info":[{"award-number":["82192911"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Triptolide exhibits promising efficacy in various cancers and immune diseases while its clinical application has been strongly restricted by its severe side effects, especially cardiotoxicity. However, the underlying mechanism of triptolide\u2010induced cardiotoxicity (TIC) remains unclear. The RNA\u2010seq analysis of triptolide\u2010injured AC16 human cardiomyocyte cell line hinted that ferroptosis is involved in TIC. Further experimental validations proved that triptolide triggered ferroptosis, as evidenced by significant accumulation of lipid peroxidation (4\u2010HNE and MDA levels) and ferrous iron, as well as depletion of intracellular GSH. Furthermore, triptolide\u2010induced iron overload involved the upregulation of TF\/TRFC\/DMT1 signal axis and the degradation of ferritin, which contribute to ROS generation\n                    <jats:italic>via<\/jats:italic>\n                    Fenton reaction. In addition, inhibition of the antioxidant Nrf2\/HO\u20101 pathway was observed in TIC, which may also lead to the overproduction of lethal lipid peroxides. Mechanistically, using streptavidin\u2013biotin affinity pull\u2010down assay and computational molecular docking, we unveiled that triptolide directly binds to SLC7A11 to inactivate SLC7A11\/GPX4 signal axis. More importantly, employment of a ferroptosis inhibitor Ferrostatin\u20101 alleviated TIC by partially reversing the inhibitory effects of triptolide on SLC7A11\/GPX4 signal. Altogether, our study demonstrated that SLC7A11\/GPX4 inactivation\u2010mediated ferroptosis contributed to the pathogenesis of TIC. Combating ferroptosis may be a promising therapeutic avenue to prevent TIC.\n                  <\/jats:p>","DOI":"10.1155\/2022\/3192607","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T16:05:16Z","timestamp":1655395516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["SLC7A11\/GPX4 Inactivation\u2010Mediated Ferroptosis Contributes to the Pathogenesis of Triptolide\u2010Induced 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