Matsumoto Michinaga, Yokoyama Hirokazu, Suzuki Hidekazu, Shiraishi-Yokoyama Haruko, Hibi Toshifumi
Dept. of Internal Medicine, School of Medicine, Keio Univ., 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan.
Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G429-33. doi: 10.1152/ajpgi.00502.2004. Epub 2005 Apr 28.
Alcohol dehydrogenase (ADH) participates in the formation of retinoic acid from retinol in various organs including the gastric mucosa. However, its clinical significance still remains to be clarified. In this study, we identified the ADH isoforms responsible for the retinoic acid formation among various ADH isoforms and examined associations among the ADH activities, the retinoic acid formation level, and morphological changes in the human gastric mucosa. Human gastric samples were endoscopically obtained from 67 male subjects. Morphological changes were assessed by the Sydney system and activities of class I, III, and IV ADH isoforms were determined in each specimen. In 26 cases, levels of all-trans retinoic acid (ATRA) formation from all-trans retinol were examined. Among activities of the three ADH isoforms, class IV ADH activity was solely associated with the ATRA formation level. This association was found even when subjects' age and Helicobacter pylori infection status were adjusted. As the degrees of inflammation, atrophy, and intestinal metaplasia increased, the class IV ADH activity as well as the potential for the ATRA formation decreased. Class IV ADH is a major enzyme in the retinoic acid supply in the human gastric mucosa, and the reduction of its activity was associated with decreasing retinoic acid supply and progression of inflammation, atrophy, and intestinal metaplasia in the gastric mucosa. In that retinoic acid is a key molecule for maintaining normal morphology, the reduction of class IV ADH activity may be involved in the pathogenesis of these morphological changes in the human gastric mucosa.
酒精脱氢酶（ADH）参与包括胃黏膜在内的各个器官中视黄醇向视黄酸的转化过程。然而，其临床意义仍有待阐明。在本研究中，我们在多种ADH同工型中确定了负责视黄酸形成的ADH同工型，并检测了ADH活性、视黄酸形成水平与人胃黏膜形态变化之间的关联。通过内镜从67名男性受试者获取人胃样本。采用悉尼系统评估形态变化，并测定每个样本中I类、III类和IV类ADH同工型的活性。在26例样本中，检测了全反式视黄醇向全反式视黄酸（ATRA）的转化水平。在三种ADH同工型的活性中，只有IV类ADH活性与ATRA形成水平相关。即使对受试者的年龄和幽门螺杆菌感染状况进行校正后，这种关联依然存在。随着炎症、萎缩和肠化生程度的增加，IV类ADH活性以及ATRA形成潜力均降低。IV类ADH是人类胃黏膜视黄酸供应中的主要酶，其活性降低与视黄酸供应减少以及胃黏膜炎症、萎缩和肠化生的进展相关。鉴于视黄酸是维持正常形态的关键分子，IV类ADH活性降低可能参与了人类胃黏膜这些形态变化的发病机制。
