Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology
Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology
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DOI：
10.1371/journal.pgen.1000812
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发表时间：
2010-01-01
期刊：
影响因子：
4.5
通讯作者：
Van Houten, Bennett
中科院分区：
文献类型：
--
作者：
Haugen, Astrid C.;Di Prospero, Nicholas A.;Van Houten, Bennett
神经退行性疾病弗里德赖希共济失调 (FRDA) 是最常见的常染色体隐性遗传性共济失调，由 frataxin 基因第一个内含子中的 GAA 三联体重复扩增引起。在这种疾病中，frataxin（一种参与铁稳态的线粒体蛋白）的转录受损，导致 mRNA 和蛋白水平显着降低。与对照组相比，对 FRDA 患者的外周血样本进行了整体基因表达分析，这表明与基因毒性应激有关的表达模式发生了改变。然后，我们通过使用基因特异性定量 PCR 检测证实了基因毒性 DNA 损伤的存在，并发现这些患者血液中线粒体和核 DNA 损伤均有所增加 (p
The neurodegenerative disease Friedreich's ataxia ( FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p