Molecular mechanisms of adenosine-induced apoptosis in human HepG2 cells

作     者：Ling-fei WU~(2,4) Guo-ping LI~2 Jia-lin FENG~3 Ze-jin PU~2 ~2Department of Gastroenterology:~3Department of Information,Second Affiliated Hospital,Shantou University Medical College,Shantou 515041.China 

作者机构：Department of Gastroenterology Second Affiliated Hospital Shantou University Medical College Shantou China Department of Information Second Affiliated Hospital Shantou University Medical College Shantou China 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2006年第27卷第4期

页      面：477-484页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Project supported by the Foundation of Guangdong Science Technique Agency(№2003C30307) 

主　　题：adenosins adenosine receptor apoptosis caspase HepG2 mitochondria 

摘      要：Aim:To investigate effects of adenosine on cell proliferation and apoptosis inhuman HepG2 ***:HepG2 cells were incubated in the presence ofadenosine(0.1-5 mmol/L)for 12-48 h,and the effect of adenosine on cell prolifera-tion was evaluated by using 3-(4,5-dimethyl-2-yl)-2,5-diphenyl-2H-tetrazolium bro-mide(MTT)*** 33342 fluorescent staining,dUTP-fluoresceinisothiocyanate(FITC)fluorescence and flow cytometric analysis techniques wereused to observe cell *** effects of adenosine receptor(A1,A2a,A3and nonspecific receptor)antagonists(8-cpt,DMPX,MRS 1191,and theophylline)and an adenosine transporter protein inhibitor(dipyridamole)on adenosine-in-duced cell apoptosis were *** membrane potential was ana-lyzed using DePsipher fluorescent staining,and caspase activity was detectedusing a Fluorometric assay kit and a fluorescence microplate ***:Adenosine significantly reduced cell viability in a dose-and *** cytotoxicity of adenosine was related to the induction of cell *** adenosine receptor antagonists had no effect on cell ***,dipyridamole significantly reduced the percentage of adenosine-induced apoptoticcells from 27.3% to 7.1%(P0.05).At 48 h after treatment,3 mmol/L adenosineincreased caspase-3 activity 3.5-fold;dipyridamole markedly decreased caspase-3 activity 1.6-fold,and decreased apoptotic cell *** HepG2 cells weretreated with 3 mmol/L adenosine,mitochondrial membrane potential and theactivity of caspase-8 or-9 remained ***:Our results suggestthat adenosine-induced apoptosis in HepG2 cells is related to intracellular eventsrsther than cell surface receptors,and that a caspase-3 cascade activation isrequired,which is not mediated via a mitochondrial pathway.