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作者

Xing, Wen-Jing Kong, Fan-Juan Li, Guang-Wei Qiao, Kun Zhang, Wei-Hua Zhang, Li Bai, Shu-Zhi Xi, Yu-Hui Li, Hong-Xia Tian, Ye Ren, Huan Wu, Ling-Yun Wang, Rui Xu, Chang-Qing

作者单位

Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin, China Immunology Harbin Medical University Department of Oncology, Taishan Medical University, Taian, China Departments of Pathophysiology Department of Pathophysiology, Qiqihar Medical University, Qiqihar Department of Biology, Lakehead University, ON, Canada

刊名

Clinical & Experimental Pharmacology & Physiology

年份

2011

卷号

Vol.38 No.9

页码

605

ISSN

0305-1870

摘要

1. Calcium-sensing receptors exist in a variety of tissues. In 2010, we first identified its functional expression in Buffalo rat liver cells and demonstrated that the activation of CaSR was involved in an increased intracellular calcium through the Gq subunit-phospholipase C-inositol triphosphate pathway. However, its role and related mechanism in hepatic ischaemia/reperfusion injury is still unclear. 2. Therefore, in the present study, BRL cells were incubated in ischaemia-mimetic solution ...更多

1. Calcium-sensing receptors exist in a variety of tissues. In 2010, we first identified its functional expression in Buffalo rat liver cells and demonstrated that the activation of CaSR was involved in an increased intracellular calcium through the Gq subunit-phospholipase C-inositol triphosphate pathway. However, its role and related mechanism in hepatic ischaemia/reperfusion injury is still unclear. 2. Therefore, in the present study, BRL cells were incubated in ischaemia-mimetic solution for 4 h, then reincubated in the normal culture medium for 10 h to establish a simulated I/R model. We assayed the apoptotic ratio of BRL cells by flow cytometry and Hoechst 33342 staining; analyzed the expression of CaSR, cytochrome c , caspase-3, Bcl-2, Bax, extracellular signal-regulated protein kinase , and p38 by Western blotting; and measured the concentration of intracellular calcium by laser-scanning confocal microscopy. 3. The results showed that simulated I/R increased the expression of CaSR and induced apoptosis in BRL cells. GdCl3, a specific activator of CaSR, further increased CaSR expression, intracellular calcium, and apoptosis in BRL cells during I/R. The activation of CaSR downregulated Bcl-2 expression, upregulated Cyt- c, caspase-3, and Bax expressions, and promoted p38 and ERK-1/2 phosphorylation. 4. In conclusion, increased CaSR expression plays a vital role in apoptosis induced by I/R injury, in which its mechanism is related with calcium overload and the activation of the mitochondrial and mitogen-activated protein kinase apoptotic pathways. The regulation of CaSR activity might serve as a novel pharmacological target to prevent and treat liver disease.收起

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