Ma Xiaodi, Ming Hewei, Liu Lexin, Zhu Jiahui, Pan Lang, Chen Yu, Xiang Yang
School of Basic Medicine, Central South University, Changsha 410078, China.
Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China.
Antioxidants (Basel). 2022 May 9;11(5):933. doi: 10.3390/antiox11050933.
As the organ executing gas exchange and directly facing the external environment, the lungs are challenged continuously by various stimuli, causing the disequilibration of redox homeostasis and leading to pulmonary diseases. The breakdown of oxidants/antioxidants system happens when the overproduction of free radicals results in an excess over the limitation of cleaning capability, which could lead to the oxidative modification of macromolecules including nucleic acids. The most common type of oxidative base, 8-oxoG, is considered the marker of DNA oxidative damage. The appearance of 8-oxoG could lead to base mismatch and its accumulation might end up as tumorigenesis. The base 8-oxoG was corrected by base excision repair initiated by 8-oxoguanine DNA glycosylase-1 (OGG1), which recognizes 8-oxoG from the genome and excises it from the DNA double strand, generating an AP site for further processing. Aside from its function in DNA damage repairment, it has been reported that OGG1 takes part in the regulation of gene expression, derived from its DNA binding characteristic, and showed impacts on inflammation. Researchers believe that OGG1 could be the potential therapy target for relative disease. This review intends to make an overall summary of the mechanism through which OGG1 regulates gene expression and the role of OGG1 in pulmonary diseases.
作为执行气体交换并直接面对外部环境的器官,肺不断受到各种刺激的挑战,导致氧化还原稳态失衡并引发肺部疾病。当自由基的过度产生导致超过清除能力的限制时,氧化剂/抗氧化剂系统就会崩溃,这可能导致包括核酸在内的大分子发生氧化修饰。最常见的氧化碱基8-氧代鸟嘌呤(8-oxoG)被认为是DNA氧化损伤的标志物。8-oxoG的出现可能导致碱基错配,其积累最终可能导致肿瘤发生。8-氧代鸟嘌呤DNA糖基化酶-1(OGG1)启动碱基切除修复来纠正8-oxoG碱基,OGG1从基因组中识别8-oxoG并将其从DNA双链中切除,产生一个无嘌呤嘧啶位点以供进一步处理。除了在DNA损伤修复中的作用外,据报道OGG1还因其DNA结合特性参与基因表达的调控,并对炎症产生影响。研究人员认为OGG1可能是相关疾病的潜在治疗靶点。本综述旨在对OGG1调节基因表达的机制以及OGG1在肺部疾病中的作用进行全面总结。