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HIV-1 Tat蛋白对DNA修复基因及细胞周期相关基因表达的影响
  • ISSN号:1004-0188
  • 期刊名称:《西南国防医药》
  • 时间:0
  • 分类:R512.91[医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]解放军第452医院,四川成都610021, [2]军事医学科学院放射与辐射医学研究所,北京100850
  • 相关基金:国际原子能机构合作项目(12510/R0);国家自然科学基金项目(30400120)
中文摘要:

目的:探讨HIV-1Tat蛋白对DNA修复基因及细胞周期相关基因表达影响。方法:使用包含102个与DNA损伤修复和细胞周期相关的基因微阵列检测人横纹肌肉瘤细胞(TE671)及已转染tat基因的TE671细胞(TT2)基因表达谱的改变;使用半定量RT—PCR分析DNA-PKcs在mRNA水平表达;Western印迹法检测DNA-PKcs表达变化;荧光染色法检测电离辐射后细胞凋亡。结果:在基因芯片的检测中,发现与DNA损伤修复及细胞周期调控相关的6个基因CdC25C、KIF2C、CdC20、DNA-PKcs、CTS1、WEE1在转染tal基因的细胞中表达下调;DNA-PKcs的表达在表达Tat蛋白细胞中不论是在mRNA和蛋白水平均被抑制;接受电离辐射后,表达Tat蛋白的细胞凋亡增加。结论:HIV-1 Tat蛋白使细胞对电离辐射敏感,部分通过抑制DNA-PKcs表达来降低DNA双链断裂的修复能力,本研究为了解AIDS合并肿瘤患者对放射治疗敏感性提供了重要实验数据。

英文摘要:

Objective: To explore effects of HIV - I Tat protein on expression of DNA repair genes and cell cycle related genes. Methods : A human rhabdomyosarcoma cell lines TE671 and TI'2 cells transfected with tat gene of the HIV - 1 strain were employed in this study. Microarray, which contains the oligonueleotide probes corresponding to 102 human DNA repair genes and cell cycle - related genes, was used to analyze the changes of gene expression in above two cell lines. The DNA - PKcs expression on mRNA and protein level was analyzed by RT - PCR and Western blot, respectively;the extent of apoptosis induced by ionizing radiation in Tat - expressing cells was detected by fluorescence staining. Results: Microarray assay demonstrated that cell cycle related genes CdC25C, KIF2C, CdC20, DNA - PKes, CTS1 and WEE1 were down - regulated in Tat - expressing TI'2 cells;DNA - PKcs expression was inhibited whether on mRNA or on protein level. Furthermore, the extent of apoptosis induced by ionizing radiation in Tat - expressing cells was significantly higher than that in control cells. Conclusion : HIV - 1 Tat protein may sensitize cells to ionizing radiation via at least partially depressing DNA - PKcs expression to lower repair ability of a cell following DNA double - strand break. Dysregulated cell cycle checkpoint in Tat - expressing cells could provide new information to understand the radiation responsiveness of AIDS patients with cancer to radiotherapy.

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期刊信息
  • 《西南国防医药》
  • 中国科技核心期刊
  • 主管单位:成都军区联勤部卫生部
  • 主办单位:成都军区医学科学技术委员会
  • 主编:牛文忠
  • 地址:成都市天仙桥北路12号
  • 邮编:610021
  • 邮箱:xinanguofang@126.com,mjnfsw@sina.com
  • 电话:028-86598539 86598516
  • 国际标准刊号:ISSN:1004-0188
  • 国内统一刊号:ISSN:51-1361/R
  • 邮发代号:
  • 获奖情况:
  • 连续四次获得军队优秀医学期刊一等奖
  • 国内外数据库收录:
  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,中国中国科技核心期刊
  • 被引量:16907