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Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes

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Abstract

Cardiomyocytes apoptosis following reperfusion injury causes irreversible damage to cardiac function. Understanding the mechanisms underlying cardiomyocytes death under these conditions can be helpful to identify strategies to abrogate such detrimental effects. Stem cell-specific proteins and regulatory pathways become important in understanding reparative processes in the myocardium. One such regulatory protein named nucleostemin (NS) has vital roles in cardiac ischemia. Although the relationship between NS and cell apoptosis has been studied, it is unknown how NS is controlled and how it participates in cardiomyocytes apoptosis induced by ischemia reperfusion (I/R). In the present study, we aimed to investigate the direct role of NS in myocardial I/R. In vivo, NS was highly expressed in cardiac tissues after I/R. Double immunofluorescent staining showed that NS located in the nucleolar of cardiomyocytes and correlated with cardiomyocytes apoptosis. Furthermore, in vitro primary rat cardiomyocytes increased NS expression induced by hypoxia-reoxygenation (H/R) treatment, in line with results in vivo. Suppression of NS expression by siNS promoted the expression of terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)-positive cells p53 and cleaved caspase-3, which demonstrates I/R may require increased expression of NS to suppress p53 activation and maintain cardiomyocytes survival.

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Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (Nos. 81401365, 81373223, 81200918, 81172879), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Nantong University graduate scientific and technological innovation projects (No. YKS14010).

Conflict of interest

The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Chi Zhang, Chao Zhang & Xiang Wu

    2. Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Jiahai Shi, Long Qian, Kunpeng Wu, Chen Yang & Daliang Yan

    3. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Xiaojuan Liu

    4. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

      Chi Zhang, Jiahai Shi, Long Qian, Chao Zhang, Kunpeng Wu, Chen Yang, Daliang Yan, Xiang Wu & Xiaojuan Liu

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    1. Chi Zhang
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    Correspondence to Xiang Wu.

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    Editor: Tetsu Okamoto

    Chi Zhang, Jiahai Shi, Xiang Wu and Xiaojuan Liu contributed equally to this work.

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    Zhang, C., Shi, J., Qian, L. et al. Nucleostemin exerts anti-apoptotic function via p53 signaling pathway in cardiomyocytes. In Vitro Cell.Dev.Biol.-Animal 51, 1064–1071 (2015). https://doi.org/10.1007/s11626-015-9934-7

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