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咖啡因抑制由紫外光引起的hRRM1和hRRM2的受激转录

发表时间:2013-09-15  浏览量:866  下载量:452
全部作者: 曾珍,王丹,王子天,周征
作者单位: 湖南大学生物学院
摘 要: 研究以HeLa细胞作为人体细胞模型,在给予或者不给予咖啡因处理的条件下,使其受到紫外光辐射。首先通过集落形成实验证实HeLa细胞在受到紫外光辐射后,咖啡因促使其凋亡。然后通过对比2种不同条件下,受ATM-ATR调控的基因的转录变化,发现了CHK1,p53,E2F1和核苷酸还原酶(ribonucleotide reductase,RNR)亚基基因hRRM1,hRRM2及p53R2转录受咖啡因的影响。结果显示,在HeLa细胞受到紫外光刺激后,咖啡因使CHK1及p53基因的转录较显著增加,可促使HeLa细胞的细胞周期停止和程序性凋亡。同时,咖啡因还使RNR亚基基因中hRRM1和hRRM2的受激转录受到明显抑制,从而抑制紫外光引起的脱氧核苷三磷酸(dNTP)库的增加。研究阐明,咖啡因通过抑制2种RNR亚基基因的受激转录阻碍dNTP库的增加,影响DNA损伤修复的进行,从而不利于细胞在经紫外辐射后的生存,也降低了细胞带着未修复的DNA损伤继续生存以致突变和癌变的可能。
关 键 词: 分子生物学;DNA损伤应答;核苷酸还原酶;紫外光;咖啡因
Title: Caffeine suppresses the UV-induced transcriptional response of hRRM1 and hRRM2 in HeLa cells
Author: ZENG Zhen, WANG Dan, WANG Zitian, ZHOU Zheng
Organization: College of Biology, Hunan University
Abstract: Our data have demonstrated that caffeine reduces the UV survival of HeLa cells which was tested by the colony-forming assay. Since caffeine inhibits the activity of the ATM-ATR mediated DNA damage response (DDR) network, we speculate that the UV-induced transcriptional response of genes regulated by this network may be influenced by caffeine. Our data display that the mRNA level of several genes, regulated by ATM-ATR DDR network, is affected by caffeine in HeLa cells following UV irradiation. Caffeine upregualtes the transcription of CHK1 and p53 but suppresses the transcription of hRRM1 and hRRM2, which code two ribonucleotide reductase (RNR) that significantly affect dNTP pool in human cells. Since the repair of UV-caused DNA lesions requires increased dNTP supply, repressed expression of ribonucleotide reductases results in reduced DNA damage repair efficiency, which causes human cells more likely to trigger apoptosis. Our data suggest that caffeine promotes the apoptosis of UV-treated HeLa cells by repressing the expression of hRRM1 and hRRM2, implying that the lower cancer risk results from decreased UV survival of human cells influenced by caffeine.
Key words: molecular biology; DNA damage response; ribonucleotide reductase; ultraviolet light; caffeine
发表期数: 2013年9月第17期
引用格式: 曾珍,王丹,王子天,等. 咖啡因抑制由紫外光引起的hRRM1和hRRM2的受激转录[J]. 中国科技论文在线精品论文,2013,6(17):1600-1606.
 
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