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Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca2+‑ATPase

  • Authors:
    • Zhidong Li
    • Jia Guo
    • Yunfei Bian
    • Mingsheng Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Cardiology, Shanxi Medical University First Hospital, Taiyuan, Shanxi 030001, P.R. China, Department of Cardiology, Shanxi Medical University Second Hospital, Taiyuan, Shanxi 030001, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 107
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    Published online on: December 1, 2020
       https://doi.org/10.3892/mmr.2020.11746
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Abstract

Intermedin (IMD) is a calcitonin/calcitonin‑related peptide that elicits cardioprotective effects in a variety of heart diseases, such as cardiac hypertrophy and heart failure. However, the molecular mechanism of IMD remains unclear. The present study investigated the effects of IMD on neonatal rat ventricular myocytes treated with thapsigargin. The results of the present study demonstrated that thapsigargin induced apoptosis in cardiomyocytes in a dose‑ and time‑dependent manner. Thapsigargin induced endoplasmic reticulum stress, as determined by increased expression levels of 78‑kDa glucose‑regulated protein, C/EBP‑homologous protein and caspase‑12, which were dose‑dependently attenuated by pretreatment with IMD. In addition, IMD treatment counteracted the thapsigargin‑induced suppression of sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA) activity and protein expression levels, and cytoplasmic Ca2+ overload. IMD treatment also augmented the phosphorylation of phospholamban, which is a crucial regulator of SERCA. Additionally, treatment with the protein kinase A antagonist H‑89 inhibited the IMD‑mediated cardioprotective effects, including SERCA activity restoration, anti‑Ca2+ overload, endoplasmic reticulum stress inhibition and antiapoptosis effects. In conclusion, the results of the present study suggested that IMD may protect cardiomyocytes against thapsigargin‑induced endoplasmic reticulum stress and the associated apoptosis at least partly by activating the protein kinase A/SERCA pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Li Z, Guo J, Bian Y and Zhang M: Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase. Mol Med Rep 23: 107, 2021.
APA
Li, Z., Guo, J., Bian, Y., & Zhang, M. (2021). Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase. Molecular Medicine Reports, 23, 107. https://doi.org/10.3892/mmr.2020.11746
MLA
Li, Z., Guo, J., Bian, Y., Zhang, M."Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase". Molecular Medicine Reports 23.2 (2021): 107.
Chicago
Li, Z., Guo, J., Bian, Y., Zhang, M."Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase". Molecular Medicine Reports 23, no. 2 (2021): 107. https://doi.org/10.3892/mmr.2020.11746
Copy and paste a formatted citation
x
Spandidos Publications style
Li Z, Guo J, Bian Y and Zhang M: Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase. Mol Med Rep 23: 107, 2021.
APA
Li, Z., Guo, J., Bian, Y., & Zhang, M. (2021). Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase. Molecular Medicine Reports, 23, 107. https://doi.org/10.3892/mmr.2020.11746
MLA
Li, Z., Guo, J., Bian, Y., Zhang, M."Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase". Molecular Medicine Reports 23.2 (2021): 107.
Chicago
Li, Z., Guo, J., Bian, Y., Zhang, M."Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase". Molecular Medicine Reports 23, no. 2 (2021): 107. https://doi.org/10.3892/mmr.2020.11746
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