β-8-Oxoguanine DNA Glycosylase Overexpression Reduces Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis Through the JNK Signaling Pathway in Human Bronchial Epithelial Cells

Abstract

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.