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首页> 外文期刊>International Journal of Genomics >The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells
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The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells

机译：基因酞酞对人细胞基因组DNA甲基化的影响

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摘要

Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 muM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p < 0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFkappaB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugscan have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health.
机译：常用的药物可能会改变细胞的表观遗传状态，导致对人体健康的不同程度的长期影响。为了测试这一假设，我们在50毫米西酞普兰（一种常见的抗抑郁药）存在下培养HEK-293细胞，持续30天，并使用Nimblegen人DNA甲基化3x720K启动子加上CpG岛阵列进行全基因组DNA甲基化分析。总共626个基因启动子，总共25,437个询问基因（2.46％），显示出显着的差异甲基化（P <0.01）;其中，272例是甲甲基化，354例在处理的与对照中高甲基化。使用巧精力途径分析，我们发现差异调节的主要基因网络和信号通路包括参与神经系统发育和功能和细胞生长和增殖的那些。涉及抑郁症的基因以及涉及核酸代谢，小分子生物化学和细胞周期调节的遗传网络被显着修饰。基于其下游靶的差异甲基化预测上游调节因子如BDNF，FSH和NFKappab的参与。该研究验证了我们的假设，即医药药物植物有偏离目标表观遗传效应，并揭示受影响的网络和途径。我们将本研究视为理解处方药对人体健康的长期表观遗传后果的第一步。

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  • 来源
    《International Journal of Genomics》 |2018年第2期|共12页
  • 作者

    Riva R. Kanherkar; Bruk Getachew; Joseph Ben-Sheetrit;

  • 作者单位

    Epigenetics Laboratory Department of Anatomy Howard University 520 W St. NW Washington DC 20059 USA;

    Department of Pharmacology Howard University 520 W St. NW Washington DC 20059 USA;

    Tel-Aviv Briill Community Mental Health Center Clalit Health Services 9 Hatzvi St. 6719709 Tel-Aviv Israel;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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