{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:57Z","timestamp":1787022177163,"version":"build-2736575974"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2021JJ40476"],"award-info":[{"award-number":["2021JJ40476"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2021JJ40506"],"award-info":[{"award-number":["2021JJ40506"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["202203014395"],"award-info":[{"award-number":["202203014395"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014472","name":"Scientific Research Foundation of Hunan Provincial Education Department","doi-asserted-by":"publisher","award":["21B0414"],"award-info":[{"award-number":["21B0414"]}],"id":[{"id":"10.13039\/100014472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Homocysteine can cause damage to cardiomyocytes, but the exact mechanism underlying that injury is unknown. And, ferroptosis contributes to both the initiation and progression of cardiac diseases. This study aims to focus on homocysteine to investigate the involvement of \u03b2-catenin\/GPX4 signaling in ferroptosis of cardiomyocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, C57BL\/6 mice were utilized to establish an experimental model. Hyperhomocysteinemia was induced in the animal model by administering homocysteine at a concentration of 1.8\u2009g\/L in the drinking water. Model mice received the treatment of deferoxamine (DFO) and ferrostatin-1 (Fer-1) as therapeutic interventions. Western blot was utilized to detect \u03b2-catenin, FTH1, and GPX4. Lipid ROS, Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , and GSH were detected by biochemical assays. In addition, \u03b2-catenin and GPX4 expression were assessed by immunostaining techniques. Cell viability was assessed using CCK-8 assay, and mitochondrial damage was examined by transmission electron microscopy. ChIP combining dual luciferase reporter gene assay was performed to analyze the interaction between \u03b2-catenin protein with the promoter of GPX4 gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Homocysteine inhibited \u03b2-catenin activity and GPX4 expression, and promoted cardiomyocytes ferroptosis\n                      <jats:italic>\n                        <jats:italic>in vitro<\/jats:italic>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        <jats:italic>in vivo<\/jats:italic>\n                      <\/jats:italic>\n                      . Overexpression of \u03b2-catenin promoted the expression of GPX4 and subsequently inhibited homocysteine-induced ferroptosis in cardiomyocytes. Further, results from the ChIP assay and dual-luciferase reporter assay indicated that GPX4 acted as a target gene of \u03b2-catenin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Homocysteine induces ferroptosis in cardiomyocytes by disrupting \u03b2-catenin activity, subsequently downregulating its target gene, GPX4.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0329792","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:32:21Z","timestamp":1754501541000},"page":"e0329792","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Homocysteine induces ferroptosis in cardiomyocytes by disrupting \u03b2-catenin\/GPX4 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