{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T10:17:39Z","timestamp":1786270659320,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81774415; 82174493"],"award-info":[{"award-number":["81774415; 82174493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Doxorubicin (DOX) is an effective anticancer drug, but it has a problem of cardiotoxicity that cannot be ignored. Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/calmodulin\u2010dependent protein kinase II (CaMKII) is tightly associated with the pathological progression of DOX\u2010induced cardiotoxicity. Ubiquitin\u2010specific protease 10 (USP10) plays an important role in many biological processes and cancers. However, its association with DOX\u2010induced cardiotoxicity and CaMKII remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>H9C2 cells, HL\u20101 cells and C57BL\/6 mice were used to establish the DOX\u2010induced cardiotoxicity model, and the CaMKII\u2010specific inhibitor KN\u201093 and USP10 specific inhibitor Spautin\u20101 were used to observe the CaMKII and USP10 effect. In cell experiments, CCK\u20108 method was used to assess cell viability, LDH kit was used to assess lactate dehydrogenase expression, DCFH\u2010DA staining was used to observe changes in active oxygen content, TUNEL staining was used to observe cell apoptosis, and Western blotting method was used to detect relevant protein markers. The expression of p\u2010CaMKII and USP10 was assessed by immunofluorescence staining. In animal experiments, mouse echocardiograph was used were used to evaluate cardiac function, and HE staining and Masson staining were used to evaluate myocardial injury. Cardiomyocyte apoptosis was detected by TUNEL staining. Western blotting method was used to detect relevant protein markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that activation of CaMKII and inhibition of USP10 pathway related to DOX\u2010induced cardiotoxicity. Inhibition of CaMKII with KN\u201093 ameliorated DOX\u2010induced cardiac dysfunction and cytotoxicity. In addition, CaMKII inhibition prevented DOX\u2010induced apoptosis and ubiquitination. Furthermore, CaMKII inhibition increased USP10 expression in DOX\u2010treated mouse hearts, H9C2 cells and HL\u20101 cells. At last, the USP10 inhibitor, Spautin\u20101, blocked the regulatory effect of CaMKII inhibition on apoptosis and ubiquitination in DOX\u2010induced cardiotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings revealed that DOX\u2010induced myocardial apoptosis and activated CaMKII through cellular and animal levels, while providing a novel probe into the mechanism of CaMKII action: promoting ubiquitination by inhibiting USP10 aggravated apoptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70286","type":"journal-article","created":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:45:29Z","timestamp":1731113129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>CaMKII<\/scp>\n                    Exacerbates Doxorubicin\u2010Induced Cardiotoxicity by Promoting Ubiquitination Through\n                    <scp>USP10<\/scp>\n                    Inhibition"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5836-3882","authenticated-orcid":false,"given":"Yitong","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Children's Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"Department of Children's Respiratory Asthma Second Affiliated Hospital of Shaanxi University of Chinese Medicine  Xianyang Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Children's Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Children's Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Xijing\u00a0Hospital, Air Force Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Children's Hospital of Xi'an Jiaotong University  Xi'an Shaanxi 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