腺花素通过peroxiredoxinⅠ对端粒酶表达和细胞死亡的影响  

Effects of adenanthin to cell death and expression of telomerase through peroxiredoxin Ⅰ

作　　者：崔佳毅 曹阳[1] 雷虎[1] 徐含章[1] 吴英理[1] 

机构地区：[1]上海交通大学医学院病理生理学教研室细胞分化与凋亡教育部重点实验室,上海200025

出　　处：《上海交通大学学报（医学版）》2015年第1期36-40,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委资助项目(11JC1406500);上海市教委资助项目(13YZ028)~~

摘　　要：目的探讨腺花素对白血病细胞端粒酶的影响和作用机制。方法用不同浓度腺花素(0、2、4、6μmol/L)处理NB4-LR1细胞不同时间(0、6、12、24 h),Western blotting检测人端粒酶逆转录酶(h TERT)蛋白的表达,Real-time PCR检测h TERT mRNA水平。用RNA干扰方法在NB4-LR1细胞内降低peroxiredoxinⅠ(PrdxⅠ)的水平,Western blotting检测h TERT蛋白的表达水平。在NB4-LR1细胞内过表达h TERT,锥虫蓝拒染法检测不同浓度(2、4μmol/L)的腺花素处理NB4-LR1-h TERT-GFP、NB4-LR1-GFP细胞后,细胞的增殖和活力的改变。结果 Western blotting检测结果显示,腺花素能够呈时间-剂量依赖性抑制h TERT的表达。敲除PrdxⅠ后h TERT的表达下降。在NB4-LR1细胞过表达h TERT可以部分抑制腺花素对细胞的毒性作用但不能抑制其诱导的细胞分化。结论腺花素通过PrdxⅠ抑制端粒酶表达,促进细胞的死亡。Objective To investigate the effects of adenanthin on telomerase of leukemia NB4-LR1 ceils and relevant mechanisms. Methods NB4-LR1 ceils were treated with different concentrations of adenanthin （0, 2, 4, and 6 μmol/L） for different periods of time （0, 6, 12, and 24 h） . The expression of human telomerase reverse transcriptase （hTERT） protein was detected by Western blotting, and the expression of hTERT mRNA was detected by Real-time PCR. The RNA interference method was adopted to decrease the expression of peroxiredoxin I （Prdx I ） in NB4-LR1 cells. Then the expression of hTERT protein was detected by Western blotting, hTERT was over-expressed in NB4-LR1 cells and the NB4-LRI-hTERT-GFP and NB4-LR1-GFP ceils were treated with different concentrations of adenanthin （2 and 4μmol/L）. The variations of proliferation and viability of ceils were detected by trypan blue exclusion assay. Results The results of Western blotting showed that adenanthin inhibited the expression of hTERT in a dose-time dependent manner. The expression of hTERT decreased after Prdx I was knocked down. Over-expression of hTERT in NB4-LR1 cells partially inhibited the toxic effect of adenanthin on cells, but could not inhibit cell differentiation induced by adenanthin. Conclusion Adenanthin inhibits the expression of telomerase through Prdx I and contributes to the death of cells.

关 键 词：端粒酶 PEROXIREDOXIN I 腺花素 白血病 细胞死亡 

分 类 号：R733.7[医药卫生—肿瘤]