CaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress‑associated apoptotic pathways during ischemia/reperfusion

  • Authors:
    • Chong Liu
    • Huanming Li
    • Huishuang Zheng
    • Meili Zhai
    • Fanghao Lu
    • Shiyun Dong
    • Tao Fang
    • Weihua Zhang
  • View Affiliations

  • Published online on: June 24, 2019     https://doi.org/10.3892/ijmm.2019.4255
  • Pages: 1117-1126
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Abstract

Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca2+ ([Ca2+]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca2+]i. The calcium‑sensing receptor (CaSR), a G protein‑coupled receptor, can increase the release of [Ca2+]i from the ER through the inositol triphosphate receptor (IP3R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress‑associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl3 (a CaSR activator) was used to elevate the intracellular Ca2+ concentration, but the Ca2+ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl3, expression levels of CaSR, glucose‑regulated protein 78 (GRP78), Caspase‑12, phosphorylated JNK and Caspase‑3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCδ translocated into the ER to induce an ER stress response and participate in the ER stress‑related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress‑associated apoptotic pathways during I/R in vivo.

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September 2019
Volume 44 Issue 3

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Copy and paste a formatted citation
APA
Liu, C., Li, H., Zheng, H., Zhai, M., Lu, F., Dong, S. ... Zhang, W. (2019). CaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress‑associated apoptotic pathways during ischemia/reperfusion. International Journal of Molecular Medicine, 44, 1117-1126. https://doi.org/10.3892/ijmm.2019.4255
MLA
Liu, C., Li, H., Zheng, H., Zhai, M., Lu, F., Dong, S., Fang, T., Zhang, W."CaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress‑associated apoptotic pathways during ischemia/reperfusion". International Journal of Molecular Medicine 44.3 (2019): 1117-1126.
Chicago
Liu, C., Li, H., Zheng, H., Zhai, M., Lu, F., Dong, S., Fang, T., Zhang, W."CaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress‑associated apoptotic pathways during ischemia/reperfusion". International Journal of Molecular Medicine 44, no. 3 (2019): 1117-1126. https://doi.org/10.3892/ijmm.2019.4255