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タイトル: | Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium. |
著者: | Amanuma, Yusuke Ohashi, Shinya Itatani, Yoshiro https://orcid.org/0000-0001-7356-7065 (unconfirmed) Tsurumaki, Mihoko Matsuda, Shun Kikuchi, Osamu https://orcid.org/0000-0001-5012-5897 (unconfirmed) Nakai, Yukie Miyamoto, Shin'ichi Oyama, Tsunehiro Kawamoto, Toshihiro Whelan, Kelly A Nakagawa, Hiroshi Chiba, Tsutomu Matsuda, Tomonari https://orcid.org/0000-0002-6177-1066 (unconfirmed) Muto, Manabu https://orcid.org/0000-0002-3127-8203 (unconfirmed) |
著者名の別形: | 武藤, 学 |
発行日: | 16-Sep-2015 |
出版者: | Nature Publishing Group |
誌名: | Scientific reports |
巻: | 5 |
論文番号: | 14142 |
抄録: | 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. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/202562 |
DOI(出版社版): | 10.1038/srep14142 |
PubMed ID: | 26374466 |
出現コレクション: | 学術雑誌掲載論文等 |
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