Document Detail


Calcium-sensing receptors induce apoptosis during simulated ischemia-reperfusion in BRL cells.
MedLine Citation:
PMID:  21692826     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Calcium-sensing receptors (CaSRs) exist in a variety of tissues. In 2010, we first identified its functional expression in BRL cells and demonstrated that activation of CaSR was involved in an increased intracellular calcium through Gq-PLC-IP(3) pathway. However, its role and related mechanism in hepatic ischemia/reperfusion (I/R) injury is still unclear. Therefore, in the present study, BRL cells were incubated in ischemia-mimetic solution for 4h, then re-incubated in the normal culture medium for 10h to establish a simulated I/R model. We assayed the apoptotic ratio of BRL cells by flow cytometry and Hoechst 33342 stained; analyzed the expression of CaSR, cytochrome c (Cyt-c), caspase-3, Bcl-2, Bax, extracellular signal-regulated protein kinase (ERK), and p38 by Western blotting; and measured the concentration of intracellular calcium by laser scanning confocal microscope (LCSM). The results showed that simulated I/R increased the expression of CaSR and induced apoptosis in BRL cells. GdCl(3) , a specific activator of CaSR, further increased CaSR expression, intracellular calcium and apoptosis in BRL cells during I/R. Activation of CaSR down-regulated Bcl-2 expression, up-regulated Cyt-c, caspase-3 and Bax expression and promoted P38 and ERK1/2 phosphorylation. In conclusion, increased CaSR expression plays a vital role in apoptosis induced by I/R injury, which mechanism is related with calcium overload, and activation of mitochondrial and MAPK apoptotic pathways. Regulation of CaSR activity may serve as a novel pharmacological target to prevent and treat liver disease.
Authors:
Wen-Jing Xing; Fan-Juan Kong; Guang-Wei Li; Kun Qiao; Wei-Hua Zhang; Li Zhang; Shu-Zhi Bai; Yu-Hui Xi; Hong-Xia Li; Ye Tian; Huan Ren; Ling-Yun Wu; Rui Wang; Chang-Qing Xu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-22
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Pathophysiology, Harbin Medical University, Harbin 150086, China Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Harbin 150086, China Department of Biology, Lakehead University, Thunder Bay, Ont., Canada P7B5E1 Department of Immunology, Harbin Medical University, Harbin 150086, China Department of Pathophysiology, Qiqihar Medical University, Qiqihar 161006, China Department of Oncology, Taishan Medical University, Taian 271000, China.
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