Retinoic acid formation from retinol in the human gastric mucosa: role of class IV alcohol dehydrogenase and its relevance to morphological changes
Retinoic acid formation from retinol in the human gastric mucosa: role of class IV alcohol dehydrogenase and its relevance to morphological changes
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DOI：
10.1152/ajpgi.00502.2004
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发表时间：
2005-09-01
影响因子：
4.5
通讯作者：
Hibi, T
中科院分区：
文献类型：
--
作者：
Matsumoto, M;Yokoyama, H;Hibi, T
乙醇脱氢酶（ADH）参与包括胃粘膜在内的多种器官中视黄醇形成视黄酸的过程。但其临床意义仍有待阐明。在这项研究中，我们鉴定了各种 ADH 异构体中负责视黄酸形成的 ADH 异构体，并检查了 ADH 活性、视黄酸形成水平和人胃粘膜形态变化之间的关联。人类胃样本是通过内窥镜从 67 名男性受试者身上获取的。通过悉尼系统评估形态变化，并测定每个样本中 I、III 和 IV 类 ADH 亚型的活性。在 26 个案例中，检查了全反式视黄醇形成的全反式视黄酸 (ATRA) 的水平。在三种 ADH 亚型的活性中，IV 类 ADH 活性仅与 ATRA 形成水平相关。即使调整了受试者的年龄和幽门螺杆菌感染状态，也发现了这种关联。随着炎症、萎缩和肠化生程度的增加，IV类ADH活性以及ATRA形成的潜力降低。 IV类ADH是人胃粘膜视黄酸供应的主要酶，其活性的降低与视黄酸供应的减少以及胃粘膜炎症、萎缩和肠化生的进展有关。由于视黄酸是维持正常形态的关键分子，IV类ADH活性的降低可能参与了人胃粘膜这些形态变化的发病机制。
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.