8-Oxoguanine DNA glycosylase-1-driven DNA base excision repair: role in asthma pathogenesis.
8-Oxoguanine DNA glycosylase-1-driven DNA base excision repair: role in asthma pathogenesis.
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DOI：
10.1097/aci.0000000000000135
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发表时间：
2015-02
影响因子：
2.8
通讯作者：
Boldogh I
中科院分区：
文献类型：
--
作者：
Ba X;Aguilera-Aguirre L;Sur S;Boldogh I
提供与哮喘相关的慢性炎症和组织学改变中氧化DNA碱基损伤和修复信号的潜在病因的概述和证据。哮喘由免疫、遗传/表观遗传和环境因素引发/维持。这是一个全球性的健康问题，因为目前的治疗方法只是抑制症状，而不是预防/逆转疾病，这在很大程度上是由于对其分子机制的理解存在差距。炎症、氧化应激和DNA损伤是不可分割的现象，但它们在哮喘发病中的分子作用尚不清楚。研究发现，在氧化修饰的DNA碱基中，8-氧鸟嘌呤（8-oxoG）是最丰富的碱基之一，其在DNA和体液中的水平被认为是正在进行的哮喘过程的生物标志物。游离的8-oxoG与8-氧鸟嘌呤DNA糖基化酶-1 （OGG1）形成复合物，激活ras家族gtpase，诱导基因表达调动先天和适应性免疫系统，以及调节特应性和非特应性哮喘气道增生、高反应性和肺重塑的基因。为了防止突变，必须保持DNA的完整性，因此它的持续修复和下游信号传导“为”哮喘中的慢性炎症过程“加油”，并形成了基本机制，其阐明将允许开发新的药物靶点来预防/逆转肺部疾病。
To provide both an overview and evidence of the potential etiology of oxidative DNA base damage and repair-signaling in chronic inflammation and histological changes associated with asthma. Asthma is initiated/maintained by immunological, genetic/epigenetic and environmental factors. It is a world-wide health problem, as current therapies suppress symptoms rather than prevent/reverse the disease, largely due to gaps in understanding its molecular mechanisms. Inflammation, oxidative stress and DNA damage are inseparable phenomena, but their molecular roles in asthma pathogenesis are unclear. It was found that among oxidatively modified DNA bases, 8-oxoguanine (8-oxoG) is one of the most abundant, and its levels in DNA and body fluids are considered a biomarker of ongoing asthmatic processes. Free 8-oxoG forms a complex with 8-oxoguanine DNA glycosylase-1 (OGG1) and activates RAS-family GTPases that induce gene expression to mobilize innate and adaptive immune systems, along with genes regulating airway hyperplasia, hyper-responsiveness and lung remodeling in atopic and non-atopic asthma. DNA’s integrity must be maintained to prevent mutation, so its continuous repair and downstream signaling “fuels” chronic inflammatory processes in asthma, and forms the basic mechanism whose elucidation will allow the development of new drug targets for the prevention/reversal of lung diseases.