Intermedin protects thapsigargin‑induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco/endoplasmic reticulum Ca<sup>2+</sup>‑ATPase

Li,Zhidong; Guo,Jia; Bian,Yunfei; Zhang,Mingsheng

doi:10.3892/mmr.2020.11746

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
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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
Published online on: December 1, 2020 https://doi.org/10.3892/mmr.2020.11746
Article Number: 107
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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