Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium
| Autor: | Kelly A. Whelan, Tsutomu Chiba, Tsunehiro Oyama, Osamu Kikuchi, Toshihiro Kawamoto, Shinya Ohashi, Shun Matsuda, Shin'ichi Miyamoto, Yusuke Amanuma, Manabu Muto, Yoshiro Itatani, Hiroshi Nakagawa, Mihoko Tsurumaki, Yukie Nakai, Tomonari Matsuda |
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| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
Male Pathology medicine.medical_specialty DNA damage Gene Expression Aldehyde dehydrogenase Acetaldehyde Biology Article Mice chemistry.chemical_compound Esophagus medicine Animals Humans Deoxyguanosine Carcinogen ALDH2 Mice Knockout Mucous Membrane Multidisciplinary Ethanol Aldehyde Dehydrogenase Mitochondrial Aldehyde Dehydrogenase Epithelium 3. Good health medicine.anatomical_structure chemistry Cancer research biology.protein DNA Damage |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 N2-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 N2-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 N2-ethylidene-2′-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. |
| Databáze: | OpenAIRE |
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