Bicyclol protects HepG2 cells against D-galacto-samine-induced apoptosis through inducing heat shock protein 27 and mitochondria associated pathway  

作　　者：Xiu-qi BAO Geng-tao LIU 

机构地区：[1]Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出　　处：《Acta Pharmacologica Sinica》2010年第2期219-226,共8页中国药理学报（英文版）

摘　　要：Aim： To study the inducing effect of bicyclol on heat shock protein 27 （HSP27） and its role on anti-apoptosis in HepG2 cells intoxicated with D-galactosamine （D-GaIN）. Methods： HepG2 cells were treated with various concentrations of bicyclol and then subjected to D-GaIN intoxication. Apoptosis was assayed by hoechst 33258 staining and flow cytometry analysis. HSP27, cytochrome c, apoptosis inducing factor （AIF） and c-Jun N-terminal kinase （JNK） were assayed by Western blot. Heat shock factor 1 （HSF1） was determined by electrophoretic mobility shift assay and the interactions of HSP27 with cytochrome c and AIF were detected by co-immunoprecipitation. Results： The results showed that bicyclol induced HSP27 protein and mRNA expression in HepG2 cells in both time- and dose-dependent manners （the maximal response： 1.23 fold increase at 100 pmol/L）. Bicyclol treatment stimulated HSF1 activation and increased the HSF1-HSE binding activity （the maximal response： 2.1 fold increase at 100 μmol/L）. This inducing effect of bicyclol on HSP27 and HSF1 was markedly blocked by quercetin. Pretreatment of the cells with bicyclol markedly attenuated D-GaiN-induced apoptosis and the release of cytochrome c and AIF from mitochondria. The induced HSP27 by bicyclol suppressed the activity of caspase-3 and the phosphorylation of JNK caused by D-GaIN in HepG2 cells. All the above effect of bicyclol against D-GaiN-induced hepatocytes apoptosis were significantly reversed by quercetin. Conclusion： HSP27 is involved in the anti-hepatocytes apoptosis of bicyclol, and this effect of bicyclol-induced HSP27 is mainly through inhibition of mitochondria and JNK apoptotic pathways.Aim： To study the inducing effect of bicyclol on heat shock protein 27 （HSP27） and its role on anti-apoptosis in HepG2 cells intoxicated with D-galactosamine （D-GaIN）. Methods： HepG2 cells were treated with various concentrations of bicyclol and then subjected to D-GaIN intoxication. Apoptosis was assayed by hoechst 33258 staining and flow cytometry analysis. HSP27, cytochrome c, apoptosis inducing factor （AIF） and c-Jun N-terminal kinase （JNK） were assayed by Western blot. Heat shock factor 1 （HSF1） was determined by electrophoretic mobility shift assay and the interactions of HSP27 with cytochrome c and AIF were detected by co-immunoprecipitation. Results： The results showed that bicyclol induced HSP27 protein and mRNA expression in HepG2 cells in both time- and dose-dependent manners （the maximal response： 1.23 fold increase at 100 pmol/L）. Bicyclol treatment stimulated HSF1 activation and increased the HSF1-HSE binding activity （the maximal response： 2.1 fold increase at 100 μmol/L）. This inducing effect of bicyclol on HSP27 and HSF1 was markedly blocked by quercetin. Pretreatment of the cells with bicyclol markedly attenuated D-GaiN-induced apoptosis and the release of cytochrome c and AIF from mitochondria. The induced HSP27 by bicyclol suppressed the activity of caspase-3 and the phosphorylation of JNK caused by D-GaIN in HepG2 cells. All the above effect of bicyclol against D-GaiN-induced hepatocytes apoptosis were significantly reversed by quercetin. Conclusion： HSP27 is involved in the anti-hepatocytes apoptosis of bicyclol, and this effect of bicyclol-induced HSP27 is mainly through inhibition of mitochondria and JNK apoptotic pathways.

关 键 词：BICYCLOL heat shock protein MITOCHONDRIA c-Jun N-terminal kinase apoptosis HepG2 cells cytochrome c D-GALACTOSAMINE 

分 类 号：Q51[生物学—生物化学] Q255