Cellular distribution of endothelin-converting enzyme-1 in human tissues
Cellular distribution of endothelin-converting enzyme-1 in human tissues
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DOI：
10.1177/002215549904700403
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发表时间：
1999-04-01
影响因子：
3.2
通讯作者：
Pinet, F
中科院分区：
文献类型：
--
作者：
Korth, P;Bohle, RM;Pinet, F
内皮素转化酶-1（ECE-1）是内皮素生物合成的关键酶，催化内皮素的最终加工步骤。如ECE-1基因的靶向破坏所示，成熟内皮素必须在正常胚胎发育的特定位点产生。因此，了解ECE-1基因表达的确切模式是非常重要的。在这项研究中，我们研究了ECE-1在各种人体组织中的细胞分布，通过原位杂交和免疫组织化学。ECE-1基因的广泛表达被注意到，在正常人体组织中具有类似的mRNA和蛋白质分布模式，表明ECE-1的主要生物学作用。ECE-1水平在心血管、生殖和内分泌系统中特别高。ECE-1在所有检查器官的血管内皮细胞和各种非血管细胞，特别是一些腺细胞中有强烈和一致的标记。在睾丸间质细胞、卵巢颗粒细胞和卵泡膜细胞中检测到大量ECE-1蛋白和mRNA。在肾上腺中，ECE-1在皮质和髓质中被检测到，在肾小球中的标记最强。因此，ECE-1可能参与其他系统，如调节激素分泌，而不是专门从其前体产生ET-1。这些结果指出了目前正在开发的用于治疗心血管疾病的ECE-1抑制剂的潜在副作用。
Endothelin-converting enzyme-1 (ECE-1) is the key enzyme of endothelin biosynthesis, catalyzing the final processing step. As shown by the targeted disruption of the ECE-1 gene, mature endothelins must be produced at specific sites for normal embryonic development. Therefore, it is important to know the exact pattern of ECE-1 gene expression. In this study we investigated the cellular distribution of ECE-1 in a variety of human tissues by in situ hybridization and immunohistochemistry. Widespread expression of the ECE-1 gene was noted, with a similar distribution pattern for mRNA and protein in normal human tissues, suggesting a major biological role for ECE-1. ECE-1 levels were particularly high in the cardiovascular, reproductive, and endocrine systems. There was strong and consistent labeling for ECE-1 in the vascular endothelial cells of all organs examined and in various nonvascular cells, especially some glandular cells. A large amount of ECE-1 protein and mRNA was detected in the Leydig cells of the testis and in the granulosa and theca cells of the ovary. In the adrenal gland, ECE-1 was detected in the cortex and medulla, with the strongest labeling in the zona glomerulosa. Therefore, ECE-1 may be involved in other systems, such as the regulation of hormone secretion, rather than exclusively generating ET-1 from its precursor. These results point out the potential side effects of ECE-1 inhibitors that are currently under development for treatment of cardiovascular diseases.