Calcium-sensing receptors induce apoptosis in rat cardiomyocytes via the endo(sarco)plasmic reticulum pathway during hypoxia/reoxygenation

Fanghao Lu, Zhiliang Tian, Weihua Zhang*, Yajun Zhao, Shuzhi Bai, Huan Ren, He Chen, Xue Yu, Jingxiao Wang, Lina Wang, Hong Li, Zhenwei Pan, Ye Tian, Baofeng Yang, Rui Wang, Changqing Xu

*此作品的通讯作者

科研成果: 期刊稿件文章同行评审

30 引用 (Scopus)

摘要

The calcium-sensing receptor (CaR) is a G protein-coupled receptor. The CaR stimulation elicits phospholipase C-mediated inositol triphosphate formation, leading to an elevation in the level of intracellular calcium released from endoplasmic reticulum (ER). Depletion of ER Ca2+ leads to ER stress, which is thought to induce apoptosis. Intracellular calcium overload-induced apoptosis in cardiac myocytes during hypoxia-reoxygenation (H/Re) has been demonstrated. However, the links between CaR, ER stress and apoptosis during H/Re are unclear. This study hypothesized that the CaR could induce apoptosis in neonatal rat cardiomyocytes during H/Re via the ER stress pathway. Neonatal rat cardiomyocytes were subjected to 3 hr of hypoxia, followed by 6 hr of reoxygenation. CaR expression was elevated and the number of apoptotic cells was significantly increased, as shown by transferase-mediated dUTP nick end-labelling, with exposure to CaCl2, a CaR activator, during H/Re. The intracellular calcium concentration was significantly elevated and the Ca2+ concentration in the ER was dramatically decreased during H/Re with CaCl2; both intracellular and ER calcium concentrations were detected by laser confocal microscopy. Expression of GRP78 (glucose-regulated protein 78), the cleavage products of ATF6 (activating transcription factor 6), phospho-PERK [pancreatic ER kinase (PKR)-like ER kinase], the activated fragments of caspase-12, and phospho-JNK (c-Jun NH2-terminal kinase) were increased following exposure to CaCl2 during H/Re. Our results confirmed that the activated CaR can induce cardiomyocyte apoptosis via ER stress-associated apoptotic pathways during H/Re.

源语言英语
页(从-至)396-405
页数10
期刊Basic and Clinical Pharmacology and Toxicology
106
5
DOI
出版状态已出版 - 5月 2010
已对外发布

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