RRC ID 48112
Author 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.
Title Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium.
Journal 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.
Volume 5
Pages 14142
Published 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
Times Cited 21
DNA material pCMV-Tag2B_ALDH2 (RDB13740) pLEX_ALDH2WT (RDB13741) pLEX_ALDH2Glu504Lys (RDB13742)