Lin Ziying, Xu Wenya, Li Chunyan, Wang Yahong, Yang Lawei, Zou Bao'an, Gao Shenglan, Yao Weimin, Song Zeqing, Liu Gang
1 Clinical Research Center, Affiliated Hospital of Guangdong Medical University , Zhanjiang, China .
2 Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University , Zhanjiang, China .
DNA Cell Biol. 2017 Dec;36(12):1071-1080. doi: 10.1089/dna.2017.3769.
8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that α-OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of β-OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed β-OGG1 has the same role as α-OGG1 in protecting human bronchial epithelial cells from apoptosis and mitochondrial dysfunction. Furthermore, flow cytometry, confocal microscopy, and western blotting showed that the overexpression of β-OGG1 could block oxidant-induced apoptosis in human bronchial epithelial cells. Additionally, knocking down OGG1 enhanced oxidative damage-induced apoptosis and mitochondrial dysfunction, whereas the overexpression of β-OGG1 had the opposite effects and led to the downregulation of Bax and PARP. The antiapoptotic function of β-OGG1 involved the JNK signaling pathway. These findings suggest that β-OGG1 and α-OGG1 have a similar function on preventing oxidative damage-mediated apoptosis and mitochondrial dysfunction; these effects might be important in the molecular events underlying oxidant-induced cytotoxicity.
8-氧代鸟嘌呤DNA糖基化酶(OGG1)负责修复8-氧代-7,8-二氢鸟嘌呤(8-氧代鸟嘌呤,8-oxoG)。我们之前的研究表明,α-OGG1可保护细胞免受氧化损伤诱导的细胞凋亡和人肺癌细胞中的线粒体功能障碍。然而,β-OGG1的功能仍有待阐明。在本研究中,我们证明过表达的β-OGG1在保护人支气管上皮细胞免受细胞凋亡和线粒体功能障碍方面与α-OGG1具有相同的作用。此外,流式细胞术、共聚焦显微镜和蛋白质印迹分析表明,β-OGG1的过表达可阻断人支气管上皮细胞中氧化剂诱导的细胞凋亡。此外,敲低OGG1可增强氧化损伤诱导的细胞凋亡和线粒体功能障碍,而过表达β-OGG1则具有相反的作用,并导致Bax和PARP的下调。β-OGG1的抗凋亡功能涉及JNK信号通路。这些发现表明,β-OGG1和α-OGG1在预防氧化损伤介导的细胞凋亡和线粒体功能障碍方面具有相似的功能;这些作用可能在氧化剂诱导的细胞毒性的分子事件中很重要。