4.6 Article

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

Journal

DNA AND CELL BIOLOGY
Volume 36, Issue 12, Pages 1071-1080

Publisher

MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2017.3769

Keywords

-OGG1; mitochondrial dysfunction; apoptosis; JNK signaling pathway; BEAS-2B

Funding

  1. Natural Science Foundation of China [81600049, NSFC81570062]
  2. Guangdong Natural Science Foundation [2016A030313681]
  3. Guangdong medical University scientific research fund [M2015009]
  4. Chinese Government Scholarship (CSC)
  5. Guangdong Medical Scientific Fund [A2017010]

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8-Oxoguanine DNA glycosylase (OGG1) is responsible for repairing 8-oxo-7,8-dihydroguanine (8-oxoG). Our previous study demonstrated that -OGG1 protects cells from oxidative damage-induced apoptosis and mitochondrial dysfunction in human lung cancer cells. However, the function of -OGG1 remains to be elucidated. In this study, we demonstrated that overexpressed -OGG1 has the same role as -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 -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 -OGG1 had the opposite effects and led to the downregulation of Bax and PARP. The antiapoptotic function of -OGG1 involved the JNK signaling pathway. These findings suggest that -OGG1 and -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.

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