Cell-specific subcellular localization of soluble epoxide hydrolase in human tissues
Cell-specific subcellular localization of soluble epoxide hydrolase in human tissues
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DOI：
10.1369/jhc.5a6808.2005
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Grant, DF
中科院分区：
文献类型：
--
作者：
Enayetallah, AE;French, RA;Grant, DF
可溶性环氧化物水解酶（sEH）是具有N-末端磷酸酶活性和C-末端环氧化物水解酶活性的I相异生物质代谢酶。内源性水解酶底物包括花生四烯酸环氧化物，其参与调节血压和炎症。sEH的亚细胞定位一直存在争议。使用小鼠和大鼠肝脏的早期研究表明，sEH可能是胞质和/或过氧化物酶体。在这项研究中，我们应用免疫荧光和共聚焦显微镜使用不同的亚细胞区室的标记物，以评估sEH共定位在人体组织的阵列。结果显示，sEH在人肝细胞和肾近端小管中是胞质和过氧化物酶体，并且在其它含有sEH的组织中是胞质的，所述其它含有sEH的组织例如胰岛细胞、肠上皮、垂体前叶细胞、肾上腺、子宫内膜、淋巴滤泡、前列腺导管上皮、肺泡壁和血管。在所评价的任何组织中，sEH都不是唯一的过氧化物酶体。我们的数据表明，人类sEH亚细胞定位是组织依赖性的，并且sEH可能具有组织或细胞类型特异性功能。据我们所知，这是第一份报告显示的sEH在广泛的人体组织的亚细胞定位。
Soluble epoxide hydrolase (sEH) is a phase-I xenobiotic metabolizing enzyme having both an N-terminal phosphatase activity and a C-terminal epoxide hydrolase activity. Enclogenous hydrolase substrates include arachidonic acid epoxides, which have been involved in regulating blood pressure and inflammation. The subcellular localization of sEH has been controversial. Earlier studies using mouse and rat liver suggested that sEH may be cytosolic and/or peroxisomal. In this study we applied immunofluorescence and confocal microscopy using markers for different subcellular compartments to evaluate sEH colocalization in an array of human tissues. Results showed that sEH is both cytosolic and peroxisomal in human hepatocytes and renal proximal tubules and exclusively cytosolic in other sEH-containing tissues such as pancreatic islet cells, intestinal epithelium, anterior pituitary cells, adrenal gland, endometrium, lymphoid follicles, prostate ductal epithelium, alveolar wall, and blood vessels. sEH was not exclusively peroxisomal in any of the tissues evaluated. Our data suggest that human sEH subcellular localization is tissue dependent, and that sEH may have tissue- or cell-type-specific functionality. To our knowledge, this is the first report showing the subcellular localization of sEH in a wide array of human tissues.