SIRT1 mediates the protective function of Nkx2.5 during stress in cardiomyocytes
Autor: | Zhen Xu, Hou-Zao Chen, Zhi-Gang She, Yun-Biao Lu, Jing Xu, Wei Zheng, Shu-ting Liang, Zhu-Qin Zhang, De-Pei Liu, Ruifeng Yang, Qing-Jun Zhang, Li Li, De-Long Hao, Yu-Sheng Wei, Jie Lu, Bei-Bei Mao |
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Rok vydání: | 2013 |
Předmět: |
Genetically modified mouse
Cell Survival Physiology Apoptosis Mice Transgenic Rats Sprague-Dawley Mice Sirtuin 1 stomatognathic system Stress Physiological Physiology (medical) Animals Homeostasis Myocyte Myocytes Cardiac Transcription factor Cells Cultured Homeodomain Proteins biology Rats Up-Regulation Cell biology Doxorubicin Models Animal Sirtuin Homeobox Protein Nkx-2.5 cardiovascular system biology.protein Signal transduction Cardiology and Cardiovascular Medicine Chromatin immunoprecipitation Signal Transduction Transcription Factors |
Zdroj: | Basic Research in Cardiology. 108 |
ISSN: | 1435-1803 0300-8428 |
Popis: | Nkx2.5 plays protective roles in cardiac homeostasis and survival in the postnatal hearts. However, the underlying molecular mechanisms that mediate the protective functions of Nkx2.5 remain unknown. Here, we showed that Nkx2.5 was downregulated in response to various stresses and was required for protection against the stress-induced apoptosis of cardiomyocytes. SIRT1, a member of the sirtuin family of proteins, was found to be a direct transcriptional target of Nkx2.5 and was required for the Nkx2.5-mediated protection of cardiomyocytes from doxorubicin (DOX)-induced apoptosis. Moreover, using chromatin immunoprecipitation assays, we found that Nkx2.5 was able to bind to the SIRT1 promoter and that this binding was significantly decreased in DOX-treated mouse hearts. Furthermore, the cardiac-specific overexpression of SIRT1 decreased the DOX-induced apoptosis of cardiomyocytes in SIRT1 transgenic mouse hearts compared with the hearts of their wild-type littermates. These findings demonstrate that SIRT1 acts as a direct transcriptional target of Nkx2.5 that maintains cardiomyocyte homeostasis and survival. |
Databáze: | OpenAIRE |
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