| Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53. | |
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MedLine Citation:
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PMID: 21278141 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of clinical antineoplastic activity, but increased apoptosis has been implicated in its cardiotoxicity. Resveratrol (RES) was shown to harbor major health benefits in diseases associated with oxidative stress. In this study we hope to determine the effect of RES on DOX-induced myocardial apoptosis in mice. Methods and results Male Balb/c mice were randomized to 1 of 4 treatments: saline, RES, DOX, and RES plus DOX (10 mice in each group). DOX treatment markedly depressed the cardiac function, decreased the heart weight, body weight and the ratio of heart weight/body weight, but inversely increased the level of protein carbonyl, malondialdehyde, and serum lactate dehydrogenase, induced mitochondrial cytochrome c release and cardiomyocyte apoptosis. However, these effects of DOX were ameliorated by its combinative treatment with RES. Further studies with coimmunoprecipitation assay revealed the interaction between p53 and Sirtuin 1 (SIRT1). It was found by Western blot and electrophoretic mobility shift assay that DOX treatment increased p53 protein acetylation and cytochrome c release from mitochondria, activated p53 binding at the Bax promoter, and up-regulated Bax expression, but supplement with RES could weaken all these effects. Conclusions The protective effect of RES against DOX-induced cardiomyocyte apoptosis is associated with the up-regulation in SIRT1-mediated deacetylation of p53. |
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Authors:
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Chi Zhang; Yansheng Feng; Shunlin Qu; Xing Wei; Honglin Zhu; Qi Luo; Meidong Liu; Guangwen Chen; Xianzhong Xiao |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-27 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P. R. China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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