{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T10:58:33Z","timestamp":1782039513064,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"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":["81371632"],"award-info":[{"award-number":["81371632"]}],"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":["81671762"],"award-info":[{"award-number":["81671762"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There are increasing concerns related to the cardiotoxicity of doxorubicin in the clinical setting. Recently, melatonin has been shown to exert a cardioprotective effect in various cardiovascular diseases, including cardiotoxic conditions. In this study, we examined the possible protective effects of melatonin on doxorubicin\u2010induced cardiotoxicity and explored the underlying mechanisms related to this process. We found that in vitro doxorubicin treatment significantly decreased H9c2 cell viability and induced apoptosis as manifested by increased TUNEL\u2010positive cells, down\u2010regulation of anti\u2010apoptotic protein Bcl\u20102, as well as up\u2010regulation of pro\u2010apoptotic protein Bax. This was associated with increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potentials (MMP). In vivo, five weeks of doxorubicin treatment significantly decreased cardiac function, as evaluated by echocardiography. TUNEL staining results confirmed the increased apoptosis caused by doxorubicin. On the other hand, combinational treatment of doxorubicin with melatonin decreased cardiomyocyte ROS and apoptosis levels, along with increasing MMP. Such doxorubicin\u2010melatonin co\u2010treatment alleviated in vivo doxorubicin\u2010induced cardiac injury. Western Blots, along with in vitro immunofluorescence and in vivo immunohistochemical staining confirmed that doxorubicin treatment significantly down\u2010regulated Yes\u2010associated protein (YAP) expression, while YAP levels were maintained under co\u2010treatment of doxorubicin and melatonin. YAP inhibition by siRNA abolished the protective effects of melatonin on doxorubicin\u2010treated cardiomyocytes, with reversed ROS level and apoptosis. Our findings suggested that melatonin treatment attenuated doxorubicin\u2010induced cardiotoxicity through preserving YAP levels, which in turn decreases oxidative stress and apoptosis.<\/jats:p>","DOI":"10.1111\/jcmm.15057","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T12:49:20Z","timestamp":1582030160000},"page":"3634-3646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Melatonin attenuates doxorubicin\u2010induced cardiotoxicity through preservation of YAP expression"],"prefix":"10.1111","volume":"24","author":[{"given":"Hai\u2010ru","family":"Li","sequence":"first","affiliation":[{"name":"Department of Ultrasound The Second Affiliated Hospital of Harbin Medical University Harbin China"},{"name":"Key Laboratories of Myocardial Ischemia Mechanism and Treatment Harbin Medical University, Ministry of Education Harbin 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