Triphlorethol-a improves the non-homologous end joining and base-excision repair capacity impaired by formaldehyde
Zhang, R; Kang, KA; Piao, MJ; Kim, KC; Lee, NH; You, HJ; Hyun, JW
HERO ID
1578368
Reference Type
Journal Article
Year
2011
Language
English
PMID
| HERO ID | 1578368 |
|---|---|
| In Press | No |
| Year | 2011 |
| Title | Triphlorethol-a improves the non-homologous end joining and base-excision repair capacity impaired by formaldehyde |
| Authors | Zhang, R; Kang, KA; Piao, MJ; Kim, KC; Lee, NH; You, HJ; Hyun, JW |
| Journal | Journal of Toxicology and Environmental Health, Part A: Current Issues |
| Volume | 74 |
| Issue | 12 |
| Page Numbers | 811-821 |
| Abstract | Formaldehyde (HCHO) generates reactive oxygen species (ROS) that induce DNA base modifications and DNA strand breaks and contributes to mutagenesis and other pathological processes. DNA non-homologous end-joining (NHEJ), a major mechanism for repairing DNA double-stranded breaks (DSB) in mammalian cells, involves the formation of a Ku protein heterodimer and recruitment of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the site of DNA damage. HCHO treatment induced DSB and decreased the protein expressions of Ku 70 and phosphorylated DNA-PKcs. Triphlorethol-A reduced DNA strand breaks and restored the expression of NHEJ-related proteins. In response to oxidative DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in repair of 8-hydroxy-2'-deoxyguanosine (8-OhdG) via the base-excision repair (BER) process. In this study, HCHO significantly increased 8-OhdG levels, whereas triphlorethol-A lowered 8-OhdG levels. Suppression of 8-OhdG formation by triphlorethol-A was related to enhanced OGG1 protein expression. Triphlorethol-A also enhanced the expression of phosphorylated Akt (the active form of Akt), a regulator of OGG1, which was found to be decreased by HCHO treatment. The phosphoinositol 3-kinase (PI3K)-specific inhibitor LY294002 abolished the cytoprotective effects induced by triphlorethol-A, suggesting that OGG1 restoration by triphlorethol-A is involved in the PI3K/Akt pathway. These results suggest that triphlorethol-A may protect cells against HCHO-induced DNA damage via enhancement of NHEJ and BER capacity. |
| Doi | 10.1080/15287394.2011.567957 |
| Pmid | 21541882 |
| Wosid | WOS:000290408600006 |
| Url | /www.tandfonline.com/doi/pdf/10.1080/15287394.2011.567957 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000290408600006 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Animals; Cells, Cultured; Cricetinae; Cricetulus; DNA Breaks, Double-Stranded/drug effects; DNA Damage/drug effects; DNA Repair/ drug effects; DNA-Activated Protein Kinase/metabolism; Deoxyguanosine/analogs & derivatives/metabolism; Fibroblasts/cytology/drug effects; Formaldehyde/ toxicity; Lung/cytology/drug effects/metabolism; Phloroglucinol/ analogs & derivatives/chemistry/pharmacology; Reactive Oxygen Species/metabolism |