Browse

Human 8-oxoguanine DNA glycosylase suppresses the oxidative stress induced apoptosis through a p53-mediated signaling pathway in human fibroblasts

Cited 33 time in Web of Science Cited 35 time in Scopus
Authors
Youn, Cha-Hyung.; Song, Peter I.; Kim, Mi-Hwa; Kim, Jin Sook; Hyun, Jin-Won; Choi, Sang-Joon; Yoon, Sang Pil; Chung, Myung Hee; Chang, In-Youb; You, Ho Jin
Issue Date
2007-10-24
Publisher
American Association for Cancer Research
Citation
Mol Cancer Res. 2007 Oct;5(10):1083-98.
Keywords
*Apoptosis/geneticsCaspase 3/metabolismCaspase 7/metabolismCell Line, TumorCell SurvivalDNA Damage/geneticsDNA Glycosylases/genetics/*physiologyFibroblasts/enzymologyHumansHydrogen Peroxide/toxicity*Oxidative Stress/geneticsRNA, Small Interfering/pharmacologySignal TransductionTumor Suppressor Protein p53/antagonists & inhibitors/genetics/*metabolism
Abstract
Human 8-oxoguanine DNA glycosylase (hOGG1) is the main defense enzyme against mutagenic effects of cellular 7,8-dihydro-8-oxoguanine. In this study, we investigated the biological role of hOGG1 in DNA damage-related apoptosis induced by hydrogen peroxide (H(2)O(2))-derived oxidative stress. The down-regulated expression of hOGG1 by its small interfering RNA prominently triggers the H(2)O(2)-induced apoptosis in human fibroblasts GM00637 and human lung carcinoma H1299 cells via the p53-mediated apoptotic pathway. However, the apoptotic responses were specifically inhibited by hOGG1 overexpression. The p53-small interfering RNA transfection into the hOGG1-deficient GM00637 markedly inhibited the H(2)O(2)-induced activation of p53-downstream target proteins such as p21, Noxa, and caspase-3/7, which eventually resulted in the increased cell viability. Although the cell viability of hOGG1-knockdown H1299 p53 null cells was similar to that of the hOGG1 wild-type H1299, after the overexpression of p53 the hOGG1-knockdown H1299 showed the significantly decreased cell viability compared with that of the hOGG1 wild-type H1299 at the same experimental condition. Moreover, the array comparative genome hybridization analyses revealed that the hOGG1-deficient GM00637 showed more significant changes in the copy number of large regions of their chromosomes in response to H(2)O(2) treatment. Therefore, we suggest that although p53 is a major modulator of apoptosis, hOGG1 also plays a pivotal role in protecting cells against the H(2)O(2)-induced apoptosis at the upstream of the p53-dependent pathway to confer a survival advantage to human fibroblasts and human lung carcinomas through maintaining their genomic stability.
ISSN
1541-7786 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17951408

http://hdl.handle.net/10371/29692
DOI
https://doi.org/10.1158/1541-7786.MCR-06-0432
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse