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Alcohol Intake Provoked Cardiomyocyte Apoptosis Via Activating Calcium-Sensing Receptor and Increasing Endoplasmic Reticulum Stress and Cytosolic [Ca2+]i

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Abstract

Background

Cardiomyocyte apoptosis plays an important role in alcoholic cardiac injury. However, the association between calcium-sensing receptor (CaSR) and alcohol-induced cardiomyocyte apoptosis remain unclear. Therefore, we investigated the role and its moleculer mechanism of CaSR in rat cardiomyocyte apoptosis induced by alcohol.

Methods

Alcohol-induced cardiomyocyte apoptosis in vivo and in vitro model of rats were applied in this study. The expression of CaSR, endoplasmic reticulum stress markers and apoptosis were tested by immunohistological staining, western blot, TUNEL and flow cytometry, respectively. [Ca2+]i were detected by confocal laser scanning microscopy.

Results

Compared with the control group, alcohol intake (AI) led to abnormal arrangements of cardiomyocytes and obvious increase of myocardial apoptosis. Moreover, AI also significantly upregulated protein expression of CaSR, GRP94, caspase-12 and CHOP. Alcohol induced apoptosis of cultured cardiomyocytes of rats in a dose-dependent way. Activation of CaSR markedly enhanced cardiomyocyte apoptosis and ERS induced by alcohol, ERS inducer also significantly increased cardiomyocyte apoptosis without activating CaSR. Furthermore, GdCl3 augmented alcohol-induced increase of [Ca2+]i in cardiomyocytes, which was attenuated by NPS2390 but not 4-PBA pre-treatment.

Conclusions

Alcohol could induce cardiomyocyte apoptosis in rats in vivo and in vitro, which was mediated probably via activating CaSR, and then ERS and the increase of the cytosolic [Ca2+]i. This provides a potential target for preventing cardiomyocyte apoptosis and cardiomyopathy induced by alochol.

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Acknowledgements

The authors thank Feng XIN, Lijuan YAN and Liping LIU for the technical work in this research. This work was supported by the National Natural Science Foundation of China (81370319, 81700318).

Author Contributions

W.L. designed research and wrote the paper; W.L., M.Z. and X.Z. performed research; W.L., J.C. and X.Z. analysed data and revised the manuscript; Y.L. and X.Y. supervised the experiments, revised and approved the manuscript.

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Authors and Affiliations

  1. Department of Cardiology, First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001, PR China

    Wenxiu Liu, Meng Zhao, Xin Zhang, Jinyu Chi, Xinhua Yin & Yue Liu

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  1. Wenxiu Liu
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Liu, W., Zhao, M., Zhang, X. et al. Alcohol Intake Provoked Cardiomyocyte Apoptosis Via Activating Calcium-Sensing Receptor and Increasing Endoplasmic Reticulum Stress and Cytosolic [Ca2+]i. Cell Biochem Biophys 81, 707–716 (2023). https://doi.org/10.1007/s12013-023-01167-8

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