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Calcineurin B subunit acts as a potential agent for preventing cardiac ischemia/reperfusion injury

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Abstract

Calcineurin B subunit (CnB) is the regulatory subunit of calcineurin (Cn), a Ca2+/calmodulin-dependent serine/threonine protein phosphatase. It has been reported that mice deleting the CnB gene lose nearly all Cn activity and show poor tolerance to cardiac stress; CnB gene expression is downregulated in the hearts of rats that have suffered ischemia/reperfusion (I/R) injury. Therefore, we wonder whether injection of exogenous CnB protein can prevent the rats from suffering I/R injury. In cardiomyocytes, fluorogenic labeling shows that exogenous CnB quickly enters the cell. Pretreatment of cardiomyocytes with CnB reduces apoptosis in response to hypoxia/reoxygenation injury (an in vitro model mimicking ischemia/reperfusion injury), and CsA reverses this effect by inhibiting Cn activity. Furthermore, CnB upregulates Bcl-2 and Bcl-XL expression in the process of hypoxia/reoxygenation injury, which may contribute to protecting cardiomyocytes against apoptosis. In vivo experiments shows that pretreatment with CnB improves cardiac contractile function and reduces the frequency of arrhythmias induced by global I/R injury. These findings reveal a novel function for CnB protein in cardiac stress response and suggest a possible application of CnB in coronary disease therapy.

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Acknowledgments

This work was partially supported by the National Natural Science Foundation of China, the International Cooperation Project, the National Important Novel Medicine Research Project, and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Genetic Engineering Medicine and Biotechnology, Beijing Normal University, Beijing, 100875, China

    Junxia Guo, Jing Li, Wei Liu, Yanxia Yin & Qun Wei

  2. Beijing Key Laboratory of Bioactive Substances and Functional Foods, College of Arts and Science of Beijing Union University, Beijing, 100191, China

    Junxia Guo & Shengquan Mi

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  1. Junxia Guo
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  2. Shengquan Mi
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Correspondence to Qun Wei.

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Guo, J., Mi, S., Li, J. et al. Calcineurin B subunit acts as a potential agent for preventing cardiac ischemia/reperfusion injury. Mol Cell Biochem 370, 163–171 (2012). https://doi.org/10.1007/s11010-012-1407-7

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  • DOI: https://doi.org/10.1007/s11010-012-1407-7

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