Molecular and Cellular Biochemistry

, Volume 361, Issue 1–2, pp 123–134 | Cite as

Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress

  • Runtao Gan
  • Guangxia Hu
  • Yajun Zhao
  • Hulun Li
  • Zhanfeng Jin
  • Huan Ren
  • Shiyun Dong
  • Xin Zhong
  • Hongzhu Li
  • Baofeng Yang
  • Changqing Xu
  • Fanghao Lu
  • Weihua Zhang
Article
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Abstract

Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP3) formation, leading to an elevation in [Ca2+] i released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER function, which cause cardiomyocyte apoptosis during ischemia/reperfusion (I/R). The aim of this study was to determine whether the protection of post-conditioning (PC) from I/R heart injury involved relieving calcium-sensing receptor (CaR)-induced ER stress. Male Wistar rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. The rats were post-conditioned after the 30 min of ischemia by three cycles of 10 s of reperfusion followed by 10 s of ischemia at the onset of reperfusion. Meanwhile, GdCl3, an activator of CaR, and NPS-2390, a specific inhibitor, were administered. We found that the PC and PC with NPS-2390 groups improved the recovery of cardiac function during reperfusion compared to the IR and PC groups with GdCl3, respectively. [Ca2+] i and [Ca2+]ER were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca2+] i was significantly increased, whereas [Ca2+]ER was significantly decreased in the I/R and PC groups with GdCl3. The rate of apoptotic cells was significantly decreased as shown by TUNEL (Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling) assay in PC and PC with NPS-2390 groups compared to the I/R and PC groups with GdCl3. In the I/R and PC groups with GdCl3, the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH2-terminal kinase) were increased compared to the PC and PC with GdCl3 groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress.

Keywords

Calcium-sensing receptor (CaR) Ischemic post-conditioning Ischemic/reperfusion Endoplasmic reticulum stress (ER stress) Heart 
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Notes

Acknowledgments

This study was supported by a Yu Weihan grant for excellent young scientists at Harbin Medical University (for Weihua Zhang), the National Natural Science Foundation of China (81170289, 81170218,81170178) and Ministry of education of Heilongjiang Province (11541111).

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Runtao Gan
    • 1
  • Guangxia Hu
    • 2
  • Yajun Zhao
    • 2
  • Hulun Li
    • 6
  • Zhanfeng Jin
    • 3
  • Huan Ren
    • 5
  • Shiyun Dong
    • 2
  • Xin Zhong
    • 2
  • Hongzhu Li
    • 2
  • Baofeng Yang
    • 4
  • Changqing Xu
    • 2
    • 4
  • Fanghao Lu
    • 2
  • Weihua Zhang
    • 2
    • 4
  1. 1.Department of CardiologyThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of PathophysiologyHarbin Medical UniversityHarbinChina
  3. 3.Department of PathologyHarbin Medical UniversityHarbinChina
  4. 4.Bio-pharmaceutical Key Laboratory of Heilongjiang ProvinceHarbin Medical UniversityHarbinChina
  5. 5.Department of ImmunologyHarbin Medical UniversityHarbinChina
  6. 6.Department of NeurobiologyHarbin Medical UniversityHarbinChina

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