Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism.
In alcohol metabolism, acetaldehyde, a highly reactive intermediate that may cause cellular and DNA damages, is converted to acetate by mitochondrial aldehyde dehydrogenase ALDH2. Although the majority of ingested alcohol is eliminated in the liver, the first-pass metabolism of ethanol in the upper digestive tract is also important for prevention and management of ethanol-related gastrointestinal diseases. However, the tissue-distribution of Aldh2 in mice has been poorly investigated. In this study, therefore, we investigated the tissue-distribution of Aldh2 as well as Aldh1, Cyp1a1, Cyp2e1, and Cyp4b1 in wild type and Aldh2-null mice by immuno-histochemical analysis. The human liver and esophageal tissues were also examined. In mice, the Aldh2 protein was detected in the liver, lung, heart, kidney, testis, esophagus, stomach, colon, and pancreas, suggesting that the tissue-distribution of Aldh2 in mice is similar to that in humans. Therefore, Aldh2-null mice may be useful model animals for the investigation of alcohol metabolism and related diseases. Compared with the wild type, the expression level of Cyp2e1 was increased in the liver from Aldh2-null mice based on Western blot analysis, whereas the levels of Aldh1, Cyp1a1, and Cyp4b1 were indistinguishable. This observation suggests that a metabolite(s) of Aldh2 might down-regulate the expression of Cyp2e1 gene.
Oyama
Tsunehiro
T
Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. oyama@med.uoeh-u.ac.jp <oyama@med.uoeh-u.ac.jp>
Isse
Toyohi
T
Kagawa
Norio
N
Kinaga
Tsuyoshi
T
Kim
Yong-Dae
YD
Morita
Masaru
M
Sugio
Kenji
K
Weiner
Henry
H
Yasumoto
Kosei
K
Kawamoto
Toshihiro
T
D000438:Alcohols / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014018:Tissue Distribution
D000438:Alcohols; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial