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Title: Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium.
Authors: Amanuma, Yusuke  kyouindb  KAKEN_id
Ohashi, Shinya  kyouindb  KAKEN_id
Itatani, Yoshiro  kyouindb  KAKEN_id
Tsurumaki, Mihoko
Matsuda, Shun
Kikuchi, Osamu  kyouindb  KAKEN_id  orcid 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  kyouindb  KAKEN_id
Muto, Manabu  kyouindb  KAKEN_id
Author's alias: 武藤, 学
Issue Date: 16-Sep-2015
Publisher: Nature Publishing Group
Journal title: Scientific reports
Volume: 5
Thesis number: 14142
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.
Rights: 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(Published Version): 10.1038/srep14142
PubMed ID: 26374466
Appears in Collections:Journal Articles

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