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Involvement of dopamine D2 receptors activation in ischemic post-conditioning-induced cardioprotection through promoting PKC-ε particulate translocation in isolated rat hearts

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Abstract

Dopamine D2 receptors (DR2) are important regulators in many organs, including cardiac system. Protein kinase C (PKC) activation and translocation is associated with cardioprotection against ischemic post-conditioning (PC); however, the regulatory role of DR2 during this process has been unknown. This study hypothesized that the prevention of cardiomyocyte damage by DR2 activation is associated with PKC translocation to the cell membrane. In the present study, we found that the ischemia/reperfusion (I/R) increased the expressions of DR2 mRNA and protein, which were further enhanced by PC. Bromocriptine (DR2 agonist) up-regulated the PC-induced DR2 expressions, and Haloperidol (DR2 antagonist) reversed the increase of DR2 expressions by Bromocriptine. PC reduced I/R-induced cardiomyocytes damage, apoptosis and myocardial infarct size, and improved cardiac function. Compared with PC, Bromocriptine further enhanced the cardioprotective roles of PC, but Haloperidol canceled the protection effect of Bromocriptine. PC up-regulated PKC-ε translocation in the particulate fraction, which was further strengthened by Bromocriptine but canceled by Haloperidol. In the cytosolic fraction, the changes of the PKC-ε translocation were opposite to the particulate fraction. These findings suggest that DR2 activation provides cardioprotection via promoting PC-induced translocation of PKC-ε.

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Acknowledgments

This research is supported by the National Natural Science Foundation of China (No. 81000059, No. 81270273, No. 81270311, No. 81070123, No. 81200160), the Supporting Certificate of Heilongjiang Postdoctoral Science-Research Foundation (No. LBH-Q11054).

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Authors and Affiliations

  1. Department of Pathophysiology, Harbin Medical University, Baojian Road, Harbin, 150081, China

    Jun Gao, Hongxia Li, Shuzhi Bai, Hong Li, Bo Wu, Lina Wang, Yuhui Xi, Ye Tian, Changqing Xu & Hongzhu Li

  2. The First Hospital of Harbin, Harbin, 150010, China

    Jun Gao

  3. Department of Cerebral Palsy, Tertiary Hospital of Jiamusi University, Jiamusi, 154003, China

    Jin Guo

  4. The School of Kinesiology, Lakehead University, Thunder Bay, ON, P7B5E1, Canada

    Guangdong Yang

  5. Department of Biology, Lakehead University, Thunder Bay, ON, P7B5E1, Canada

    Rui Wang

  6. Department of Health Science, Lakehead University, Thunder Bay, ON, P7B5E1, Canada

    Lingyun Wu

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  1. Jun Gao
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  2. Jin Guo
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  3. Hongxia Li
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  5. Hong Li
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  11. Rui Wang
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  13. Changqing Xu
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  14. Hongzhu Li
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Corresponding authors

Correspondence to Changqing Xu or Hongzhu Li.

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Jun Gao and Jin Guo contributed equally to this study.

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Gao, J., Guo, J., Li, H. et al. Involvement of dopamine D2 receptors activation in ischemic post-conditioning-induced cardioprotection through promoting PKC-ε particulate translocation in isolated rat hearts. Mol Cell Biochem 379, 267–276 (2013). https://doi.org/10.1007/s11010-013-1648-0

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  • DOI: https://doi.org/10.1007/s11010-013-1648-0

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