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Electrochemical detection of specific interactions between apolipoprotein E isoforms and DNA sequences related to Alzheimer's disease.
Bioelectrochemistry ( IF 5 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.bioelechem.2019.107447
Dhésmon Lima 1 , Ana Carolina M Hacke 1 , Juliana Inaba 1 , Christiana A Pessôa 1 , Kagan Kerman 2
Affiliation  

Apolipoprotein E4 (ApoE4) has a key role on the onset and progression of Alzheimer's disease (AD), since it favours the deposition of toxic amyloid-beta (Aβ) aggregates in the brain. These effects might result from the interaction between ApoE4 and specific DNA promoters related to cellular autophagy pathways and to the expression of neuroprotective proteins, like sirtuin-1. Herein, we modified gold electrodes with mixed self-assembled monolayers of 6-mercapto-1-hexanol and thiolated DNA oligonucleotides related to CLEAR (associated with autophagic processes that enable the clearance of toxic species, such as Aβ) and SirT1 (related to the expression of sirtuin-1) promoter sequences. The interactions of the immobilized DNA sequences with isoforms of ApoE (ApoE4/ApoE3/ApoE2) were investigated by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) measurements. By monitoring current and charge transfer resistance (Rct) variations, CLEAR showed to interact specifically with ApoE4, whereas SirT1 showed a higher affinity to ApoE4 compared to ApoE3 and ApoE2. To the best of our knowledge, this is the first report about the application of electrochemical techniques to investigate the sequence-specific interaction between ApoE isoforms and CLEAR and SirT1 oligonucleotides.

中文翻译:

载脂蛋白E亚型和与阿尔茨海默氏病有关的DNA序列之间特异性相互作用的电化学检测。

载脂蛋白E4(ApoE4)在阿尔茨海默氏病(AD)的发作和进展中起关键作用,因为它有助于在大脑中沉积有毒的淀粉样β(Aβ)聚集体。这些作用可能是由于ApoE4与特定的DNA启动子之间的相互作用引起的,这些启动子与细胞自噬途径以及神经保护蛋白(如sirtuin-1)的表达有关。在本文中,我们用6-巯基-1-己醇和与CLEAR(与能清除Aβ等有毒物质的自噬过程相关的自噬过程)和SirT1(与ACL有关的自噬过程)混合的自组装单层6-巯基-1-己醇和硫醇化DNA寡核苷酸修饰了金电极。 sirtuin-1)启动子序列的表达。固定化的DNA序列与ApoE(ApoE4 / ApoE3 / ApoE2)亚型的相互作用通过差分脉冲伏安法(DPV)和电化学阻抗谱(EIS)测量进行了研究。通过监视电流和电荷转移电阻(Rct)的变化,CLEAR显示出与ApoE4的特异性相互作用,而SirT1与ApoE3和ApoE2相比,对ApoE4的亲和力更高。据我们所知,这是关于电化学技术研究ApoE亚型与CLEAR和SirT1寡核苷酸之间的序列特异性相互作用的第一份报告。而SirT1对ApoE4的亲和力高于ApoE3和ApoE2。据我们所知,这是关于电化学技术研究ApoE亚型与CLEAR和SirT1寡核苷酸之间的序列特异性相互作用的第一份报告。而SirT1对ApoE4的亲和力高于ApoE3和ApoE2。据我们所知,这是关于电化学技术研究ApoE亚型与CLEAR和SirT1寡核苷酸之间的序列特异性相互作用的第一份报告。
更新日期:2019-12-23
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