β-8-Oxoguanine DNA Glycosylase Overexpression Reduces Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis Through the JNK Signaling Pathway in Human Bronchial Epithelial Cells
β-8-Oxoguanine DNA Glycosylase Overexpression Reduces Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis Through the JNK Signaling Pathway in Human Bronchial Epithelial Cells
复制标题
β-8-氧化鸟嘌呤 DNA 糖基化酶过表达通过人支气管上皮细胞中的 JNK 信号通路减少氧化应激诱导的线粒体功能障碍和细胞凋亡
DOI：
10.1089/dna.2017.3769
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发表时间：
2017
影响因子：
3.1
通讯作者：
Liu Gang
中科院分区：
文献类型：
--
作者：
Lin Ziying;Xu Wenya;Li Chunyan;Wang Yahong;Yang Lawei;Zou Bao'an;Gao Shenglan;Yao Weimin;Song Zeqing;Liu Gang
8-氧鸟嘌呤DNA糖基化酶（OGG1）负责修复8-氧-7,8-二氢鸟嘌呤（8-oxoG）。我们之前的研究表明α-OGG1保护细胞免受氧化损伤诱导的细胞凋亡和线粒体功能障碍。然而，β-OGG1的功能仍有待阐明。在本研究中，我们证明了过表达的β-OGG1与α-OGG1在保护人支气管上皮细胞凋亡和线粒体功能障碍方面具有相同的作用。此外，流式细胞术、共聚焦显微镜和western blotting结果显示，β-OGG1过表达可阻断氧化诱导的支气管上皮细胞凋亡。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β-OGG1的过表达则具有相反的作用，可导致Bax和PARP的下调。β-OGG1的抗凋亡功能涉及JNK信号通路。这些结果表明，β-OGG1和α-OGG1在防止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；这些效应可能在氧化诱导细胞毒性的分子事件中是重要的。
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.