論文 - 詳細
| RRC ID | 48112 |
|---|---|
| 著者 | Amanuma Y, Ohashi S, Itatani Y, Tsurumaki M, Matsuda S, Kikuchi O, Nakai Y, Miyamoto S, Oyama T, Kawamoto T, Whelan KA, Nakagawa H, Chiba T, Matsuda T, Muto M. |
| タイトル | Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium. |
| ジャーナル | Sci Rep |
| Abstract |
Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N(2)-ethylidene-2'-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N(2)-ethylidene-2'-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. |
| 巻・号 | 5 |
| ページ | 14142 |
| 公開日 | 2015-9-16 |
| DOI | 10.1038/srep14142 |
| PII | srep14142 |
| PMID | 26374466 |
| PMC | PMC4570974 |
| MeSH | Acetaldehyde / toxicity* Aldehyde Dehydrogenase / genetics* Aldehyde Dehydrogenase / metabolism Aldehyde Dehydrogenase, Mitochondrial Animals DNA Damage / drug effects* Esophagus* Ethanol / adverse effects Gene Expression Humans Keratinocytes / drug effects Keratinocytes / metabolism Male Mice Mice, Knockout Mucous Membrane / drug effects* Mucous Membrane / metabolism* Mucous Membrane / pathology |
| IF | 3.998 |
| 引用数 | 21 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMV-Tag2B_ALDH2 (RDB13740) pLEX_ALDH2WT (RDB13741) pLEX_ALDH2Glu504Lys (RDB13742) |