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Human 8-oxoguanine DNA glycosylase suppresses the oxidative stress induced apoptosis through a p53-mediated signaling pathway in human fibroblasts
DC Field | Value | Language |
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dc.contributor.author | Youn, Cha-Hyung. | - |
dc.contributor.author | Song, Peter I. | - |
dc.contributor.author | Kim, Mi-Hwa | - |
dc.contributor.author | Kim, Jin Sook | - |
dc.contributor.author | Hyun, Jin-Won | - |
dc.contributor.author | Choi, Sang-Joon | - |
dc.contributor.author | Yoon, Sang Pil | - |
dc.contributor.author | Chung, Myung Hee | - |
dc.contributor.author | Chang, In-Youb | - |
dc.contributor.author | You, Ho Jin | - |
dc.date.accessioned | 2010-01-12T05:32:15Z | - |
dc.date.available | 2010-01-12T05:32:15Z | - |
dc.date.issued | 2007-10-24 | - |
dc.identifier.citation | Mol Cancer Res. 2007 Oct;5(10):1083-98. | en |
dc.identifier.issn | 1541-7786 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17951408 | - |
dc.identifier.uri | https://hdl.handle.net/10371/29692 | - |
dc.description.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. | en |
dc.language.iso | en | en |
dc.publisher | American Association for Cancer Research | en |
dc.subject | Caspase 3/metabolism | en |
dc.subject | Caspase 7/metabolism | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cell Survival | en |
dc.subject | DNA Damage/genetics | en |
dc.subject | DNA Glycosylases/genetics/*physiology | en |
dc.subject | Fibroblasts/enzymology | en |
dc.subject | Humans | en |
dc.subject | Hydrogen Peroxide/toxicity | en |
dc.subject | RNA, Small Interfering/pharmacology | en |
dc.subject | Signal Transduction | en |
dc.subject | Tumor Suppressor Protein p53/antagonists & inhibitors/genetics/*metabolism | en |
dc.subject | Apoptosis/genetics | - |
dc.subject | Oxidative Stress/genetics | - |
dc.title | Human 8-oxoguanine DNA glycosylase suppresses the oxidative stress induced apoptosis through a p53-mediated signaling pathway in human fibroblasts | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 윤차경 | - |
dc.contributor.AlternativeAuthor | 김미화 | - |
dc.contributor.AlternativeAuthor | 김진숙 | - |
dc.contributor.AlternativeAuthor | 현진원 | - |
dc.contributor.AlternativeAuthor | 최상준 | - |
dc.contributor.AlternativeAuthor | 윤상필 | - |
dc.contributor.AlternativeAuthor | 정명희 | - |
dc.contributor.AlternativeAuthor | 장인엽 | - |
dc.contributor.AlternativeAuthor | 유호진 | - |
dc.identifier.doi | 10.1158/1541-7786.MCR-06-0432 | - |
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