| Co-Investigator(Kenkyū-buntansha) |
OYAMA Tsunehiro University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (00309965)
TOYOHI Isse University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 助手 (80341494)
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| Research Abstract |
[Introduction] In consequence of decreased acetaldehyde metabolism, an aldehyde dehydrogenase 2 (ALDH2) allele is associated with alcohol-induced flushing, and is also positively related to liver disease, oral cancer and esophageal cancer. It is also well-known that half of the Japanese population shows alcohol-induced flushing. Mice (C57BL/6) lacking Aldh2 (Aldh2 knock-out mice ; Aldh2 KO mice) should be useful model animals to investigate the effects of ALDH2 deficiency. Thus, we investigated the tissue distribution of Aldh2 as well as Aldh1 and Cyp enzymes in wild-type mice and the expression levels of the enzymes were compared with those in Aldh2 KO mice to investigate the effects of Aldh2 deficiency on the expression of enzymes involved in alcohol metabolism. We also examined the expressions of ALDH and CYP enzymes in the human esophageal epithelium.
[Materials and Methods](1)Immunohistochemical staining for the detection of Aldh1,Aldh2,Cyp1a1,Cyp2e1 and Cyp4b1 was performed using
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organs from at least 5 wild-type mice. (male C57BL/6 mice, 6-10 weeks of age) and 5 Aldh2 KO mice (6-10 weeks of age). Nine organs (lung, heart, kidney, testis, liver, esophagus, stomach, colon and pancreas) were dissected from each mouse. Organs were stained using the avidin-biotin complex (ABC) method.
(2)Cytosolic proteins from mouse livers were used for the detection of Aldh1, mitochondrial proteins for Aldh2, and microsomes for Cyp1a1,Cyp2e1 and Cyp4b1. These proteins were used for Western blot analysis.
(3)The ALDH2 expression was analyzed in the human specimens of esophageal epithelium from 51 esophageal cancer patients. Human specimens were stained using the avidin-biotin complex (ABC) method with a peroxidase-labeled streptavidin-biotin antibody (LSAB) kit.
[Results and conclusions] All Aldh and Cyp enzymes were detected in multiple organs, in particular, they were abundantly expressed in the liver and gastrointestinal tract in wild-type and Aldh2 KO mice, although Aldh2 was not expressed in the organs of Aldh2 KO mice. In Western blot analysis, the expression level of Cyp2e1 was enhanced in the liver of Aldh2 KO mice. The results of ALDH2 immunostaining in the 51 esophageal epithelium samples were compared with both the drinking habit and the occurrence of flushing, which are closely associated with ALDH2 deficiency. Aldh2 KO mice should be useful model animals to investigate the effects of ALDH2 deficiency, such as esophageal cancer. Less
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