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01.07.2013 | Original Contribution

SIRT1 mediates the protective function of Nkx2.5 during stress in cardiomyocytes

verfasst von: Wei Zheng, Yun-Biao Lu, Shu-Ting Liang, Qing-Jun Zhang, Jing Xu, Zhi-Gang She, Zhu-Qin Zhang, Rui-Feng Yang, Bei-Bei Mao, Zhen Xu, Li Li, De-Long Hao, Jie Lu, Yu-Sheng Wei, Hou-Zao Chen, De-Pei Liu

Erschienen in: Basic Research in Cardiology | Ausgabe 4/2013

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Abstract

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.

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Titel: SIRT1 mediates the protective function of Nkx2.5 during stress in cardiomyocytes
verfasst von: Wei Zheng
Yun-Biao Lu
Shu-Ting Liang
Qing-Jun Zhang
Jing Xu
Zhi-Gang She
Zhu-Qin Zhang
Rui-Feng Yang
Bei-Bei Mao
Zhen Xu
Li Li
De-Long Hao
Jie Lu
Yu-Sheng Wei
Hou-Zao Chen
De-Pei Liu
Publikationsdatum: 01.07.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 4/2013
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-013-0364-y

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