1-脱氧甘露糖野尻霉素诱导人肝癌SMMC7721细胞发生内质网应激  

1-deoxymannojirimycin induced endoplasmic reticulum stress in hepatocellular carcinoma cell line 7721

作　　者：徐莺莺[1] 陆祎[1] 申宗侯[1] 

机构地区：[1]复旦大学上海医学院生物化学与分子生物学系,上海200032

出　　处：《复旦学报（医学版）》2006年第4期437-440,450,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(No.30370343)资助

摘　　要：目的探讨人肝癌SMMC7721细胞中1-脱氧甘露糖野尻霉素(1-deoxymannojirimycin,DMJ)对高尔基体中α-甘露糖苷酶Ⅰ活性的抑制作用与内质网应激的关系。方法人肝癌SMMC7721细胞经DMJ诱导后,用RT-PCR和Western blot检测内质网应激中的重要分子葡萄糖调节蛋白78(glucose regulated protein78,GRP78)、X盒结合蛋白1(X box binding protein1,XBP1)、C/EBP同源蛋白(C/EBP homologus protein,CHOP)及caspase-12的表达变化。结果GRP78的mRNA和蛋白质表达量升高;XBP1的mRNA发生剪接,蛋白相对分子质量从33 000变为54 000;CHOP蛋白表达量上调;caspase-12剪切激活。结论DMJ可诱导SMMC7721细胞发生内质网应激。Purpose To study the relation between the inhibition of Golgi α-1,2mannosidase Ⅰ by 1- deoxymannojirimycin（DMJ） and endoplasmic reticulum stress（ER stress） in hepatocellular cell line SMMC7721. Methods SMMC7721 cells were treated with DMJ. Then the key molecules involving in ER stress such as glucose regulated protein 78（GRP78）, X box binding protein 1 （XBP1）, C/EBP homologus protein（CHOP） and caspase-12 was analyzed on mRNA or protein levels with RT-PCR or Western blot. Results GRP78 expression on both mRNA and protein levels were upregulated, the spliced forms of XBP1 mRNA and relative protein were found, CHOP protein was increased and caspase-12 was activated in SMMC7721 with DMJ treatment. Conclusions These results suggested that DMJ could induce cellular ER stress in SMMC7721.

关 键 词：内质网应激 1-脱氧甘露糖野尻霉素 α-甘露糖苷酶Ⅰ 

分 类 号：R735.7[医药卫生—肿瘤]