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   BCL2 promotor methylation and miR-15a/16-1 upregulation is associated with sanguinarine-induced apoptotic death in rat HSC-T6 cells  
   
نویسنده zhang d.-s. ,li y.-y. ,chen x.-j. ,li y.-j. ,liu z.-y. ,xie w.-j. ,sun z.-l.
منبع journal of pharmacological sciences - 2015 - دوره : 127 - شماره : 1 - صفحه:135 -144
چکیده    Previous studies show that several pathways are involved in sanguinarine-induced apoptotic cell death,including akt downregulation,inhibition of nf-kb activation,mediation of ros production,downregulation of anti-apoptosis proteins xiap and ciap-1,upregulation of bax,and downregulation of bcl2. in this study,we found out that the quenching of ros generation by n-acetyl-l-cysteine (nac),a scavenger of ros,reversed sanguinarine-induced apoptosis effects,also we found out that sanguinarine-induced rat hepatic stellate t6 cells (hsc-t6 cells) apoptosis was correlated with the generation of increased ros,which was followed by the activation of caspase-8 (-3,-6,and -9),and the decreasing in the miltochondrial membrane potential (mmp) and the down-regulation of anti-apoptotic protein bcl-2. it is not clear whether bcl2's downregulation relates to its promoter methylation and mir-15a/16-1 expression which can bind to bcl2 3′-utr (un-translation reagon). we showed that sanguinarine-induced down regulation of bcl2 was associated with the increased methylation rate of bcl2 promotor district and the increased expression of mir-15a/16-1. hsc-t6 cells treatment with 5-aza-2'-deoxycytidine (5′-aza-cdr) impeded sanguinarine-induced bcl2 promotor district methylation and recovered bcl2's expression. over expression of bcl2 using pegfp-n1 vector decreased sanguinarine-induced hsc-t6 cells apoptotic death significantly but not completely. these observations clearly showed that bcl2 down regulation was associated with its promoter methylation and mir-15a/16-1 upregulation in sanguinarine-induced rat hsc-t6 cells. © 2014 japanese pharmacological society.
کلیدواژه Apoptosis; Methylation; MiR-15a/16-1; ROS; Sanguinarine
آدرس college of veterinary medicine,hunan agricultural university,changsha,hunan,410128, China, college of veterinary medicine,hunan agricultural university,changsha,hunan,410128, China, college of veterinary medicine,hunan agricultural university,changsha,hunan,410128, China, college of veterinary medicine,hunan agricultural university,changsha,hunan,410128, China, college of veterinary medicine,hunan agricultural university,changsha,hunan,410128, China, department of pharmaceutics,hunan university of traditional chinese medicine,xueshi road 300,changsha,hunan,410208, China, college of veterinary medicine,hunan agricultural university,changsha,hunan,410128,china,medicine resources for livestock and innovative engineering research center in veterinary medicine, China
 
     
   
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