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Article

Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy

  • Authors:
    • Hu Shan
    • Jin Wei
    • Ming Zhang
    • Lin Lin
    • Rui Yan
    • Rong Zhang
    • Yan‑He Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710004, P.R. China, Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
  • Pages: 4720-4726
    |
    Published online on: January 27, 2015
       https://doi.org/10.3892/mmr.2015.3260
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Abstract

Mitochondrial connexin 43 (Cx43) is important in cardioprotection by ischemic preconditioning; however, whether mitochondrial Cx43 is involved in mitochondrial dysfunction in the pathogenesis of dilated cardiomyopathy (DCM) remains to be elucidated. The present study was performed to investigate the changes in expression and the phosphorylation state of mitochondrial Cx43 in a rat model of DCM, and to determine whether the altered phosphorylation state of mitochondrial Cx43 was involved in mitochondrial dysfunction. A rat model of DCM was generated by daily oral administration of furazolidone (FZD) for 30 weeks. Reverse transcription polymerase chain reaction and western blot analysis revealed a decrease in the overall expression of Cx43, accompanied by reduced levels of serine 368‑phosphorylated‑Cx43 immunoreactivity in the myocardium and myocardial mitochondria. In addition, the mitochondrial membrane potential and the activities of cytochrome c oxidase, succinate dehydrogenase and protein kinase C (PKC) ε were all significantly reduced compared with those of the control group. Phorbol‑12‑myristate‑13‑acetate (PMA), a specific PKC activator, partially reversed the FZD‑induced mitochondrial Cx43 dephosphorylation at serine 368 and mitochondrial dysfunction in the cardiomyocytes. However, pretreatment with 18β‑glycerrhetinic acid, a connexin channel inhibitor, eliminated the mitochondrial protective effect of PMA in the cardiomyocytes sparsely plated without cell to cell contact. These results suggested that dephosphorylation of mitochondrial Cx43 at serine 368, due to the suppression of PKCε activity, may be a novel mechanism for mitochondrial dysfunction in the pathogenesis of DCM.
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Copy and paste a formatted citation
Spandidos Publications style
Shan H, Wei J, Zhang M, Lin L, Yan R, Zhang R and Zhu YH: Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy. Mol Med Rep 11: 4720-4726, 2015.
APA
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., & Zhu, Y. (2015). Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy. Molecular Medicine Reports, 11, 4720-4726. https://doi.org/10.3892/mmr.2015.3260
MLA
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., Zhu, Y."Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy". Molecular Medicine Reports 11.6 (2015): 4720-4726.
Chicago
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., Zhu, Y."Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy". Molecular Medicine Reports 11, no. 6 (2015): 4720-4726. https://doi.org/10.3892/mmr.2015.3260
Copy and paste a formatted citation
x
Spandidos Publications style
Shan H, Wei J, Zhang M, Lin L, Yan R, Zhang R and Zhu YH: Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy. Mol Med Rep 11: 4720-4726, 2015.
APA
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., & Zhu, Y. (2015). Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy. Molecular Medicine Reports, 11, 4720-4726. https://doi.org/10.3892/mmr.2015.3260
MLA
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., Zhu, Y."Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy". Molecular Medicine Reports 11.6 (2015): 4720-4726.
Chicago
Shan, H., Wei, J., Zhang, M., Lin, L., Yan, R., Zhang, R., Zhu, Y."Suppression of PKCε-mediated mitochondrial connexin 43 phosphorylation at serine 368 is involved in myocardial mitochondrial dysfunction in a rat model of dilated cardiomyopathy". Molecular Medicine Reports 11, no. 6 (2015): 4720-4726. https://doi.org/10.3892/mmr.2015.3260
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