Biomarkers of nucleic acid oxidation - A summary state-of-the-art.

Biomarkers of nucleic acid oxidation - A summary state-of-the-art.
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核酸氧化的生物标志物-最新技术概述。

DOI:
10.1016/j.redox.2021.101872
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发表时间:
2021-06
期刊:
影响因子:
11.4
通讯作者:
Cooke MS
Cooke MS
中科院分区:
生物学1区
文献类型:
--
作者:
Chao MR;Evans MD;Hu CW;Ji Y;Møller P;Rossner P;Cooke MS

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氧化产生的DNA损伤与多种疾病的发病机制有关。人们对其他核酸、RNA和(2 ' -脱氧-)核糖核苷酸库损伤的影响也越来越感兴趣,越来越多的证据表明,这些也可能在疾病中发挥重要作用。LC-MS/MS能够提供特定生物标志物的绝对定量,例如核和线粒体DNA中的8-oxo-7,8-二氢-2 ' -脱氧郭(8-oxodG),以及RNA中的8-oxoGuo。然而,由于需要大量的组织,限制了其在人体生物监测研究中的应用。相比之下,彗星试验所需的材料要少得多,只需5 μL的血液,提供了一种评估体内氧化应激的微创方法,但这仅限于核DNA损伤。尿液是非侵入性研究核酸衍生的氧化应激生物标志物的理想基质,并且在强有力地验证这些测量方面取得了相当大的进展,尤其是通过欧洲尿(DNA)损伤分析标准委员会的努力。对于尿液,LC-MS/MS被认为是金标准方法,尽管ELISA方法已经有所改进,但这在很大程度上仅限于8-oxodG。新兴的DNA内合组学方法,要么全面评估DNA中加合物的总数,要么绘制细胞核和线粒体基因组的DNA损伤图谱,提供了极大地提高我们对氧化损伤核酸在疾病中的机制作用的理解的潜力。氧化损伤的核酸与疾病的发病机制有关。LC-MS/MS、comet assay和ELISA是研究氧化损伤DNA的常用方法。尿氧化损伤核酸无创反映氧化应激。DNA内收组学将有助于理解活性氧损伤DNA在疾病中的作用。
Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. Increasingly, interest is also focusing upon the effects of damage to the other nucleic acids, RNA and the (2′-deoxy-)ribonucleotide pools, and evidence is growing that these too may have an important role in disease. LC-MS/MS has the ability to provide absolute quantification of specific biomarkers, such as 8-oxo-7,8-dihydro-2′-deoxyGuo (8-oxodG), in both nuclear and mitochondrial DNA, and 8-oxoGuo in RNA. However, significant quantities of tissue are needed, limiting its use in human biomonitoring studies. In contrast, the comet assay requires much less material, and as little as 5 μL of blood may be used, offering a minimally invasive means of assessing oxidative stress in vivo, but this is restricted to nuclear DNA damage only. Urine is an ideal matrix in which to non-invasively study nucleic acid-derived biomarkers of oxidative stress, and considerable progress has been made towards robustly validating these measurements, not least through the efforts of the European Standards Committee on Urinary (DNA) Lesion Analysis. For urine, LC-MS/MS is considered the gold standard approach, and although there have been improvements to the ELISA methodology, this is largely limited to 8-oxodG. Emerging DNA adductomics approaches, which either comprehensively assess the totality of adducts in DNA, or map DNA damage across the nuclear and mitochondrial genomes, offer the potential to considerably advance our understanding of the mechanistic role of oxidatively damaged nucleic acids in disease. Oxidatively damaged nucleic acids are implicated in the pathogenesis of disease. LC-MS/MS, comet assay and ELISA are often used to study oxidatively damaged DNA. Urinary oxidatively damaged nucleic acids non-invasively reflect oxidative stress. DNA adductomics will aid understanding the role of ROS damaged DNA in disease.
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发表时间: 2018-02-23
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2-氧化丙氨酸通过2-oxo-ATP的细胞内积累和ATP的耗竭诱导细胞毒性,而不是通过p38 MAPK途径诱导细胞毒性。
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