A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9
A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9
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DOI：
10.1161/01.res.87.5.e1
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发表时间：
2000-09-01
影响因子：
20.1
通讯作者：
Acton, S
中科院分区：
文献类型：
--
作者：
Donoghue, M;Hsieh, F;Acton, S
血管紧张素转换酶(ACE)的第一个人类同源物ACE2是从一个人心力衰竭心室文库的5‘端测序中鉴定出来的。ACE2有一个明显的信号肽、一个单一的金属蛋白酶活性部位和一个跨膜区。ACE2和ACE的金属蛋白酶催化结构域有42%的同源性，基因组结构的比较表明这两个基因是通过复制产生的。与更为普遍的血管紧张素转换酶不同，血管紧张素转换酶2的转录本仅在23个被检查的人体组织中发现。免疫组织化学显示ACE2蛋白主要表达于冠状动脉和肾内血管内皮细胞以及肾小管上皮细胞。活性ACE2酶是通过将N-末端裂解到跨膜区而从转基因细胞中分泌出来的。重组ACE2将血管紧张素I的羧基末端亮氨酸水解生成血管紧张素1-9，在体外经血管紧张素转换为较小的血管紧张素肽，在培养的心肌细胞中可转化为较小的血管紧张素肽。ACE2还可以裂解Des-Arg缓激肽和神经降压素，但不能裂解缓激肽或其他15种测试的血管活性和荷尔蒙多肽。赖诺普利和卡托普利对ACE2无抑制作用。ACE2在器官和细胞中的特异性表达及其对关键血管活性多肽的独特切割表明，ACE2在心脏和肾脏的局部肾素-血管紧张素系统中发挥着重要作用。本文全文可在http://www.circresaha.org.上查阅
ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was identified from 5' sequencing of a human heart failure ventricle cDNA library. ACE2 has an apparent signal peptide, a single metalloprotease active site, and a transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are 42%, identical, and comparison of the genomic structures indicates that the two genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2 transcripts are found only in heart, kidney, and testis of 23 human tissues examined. Immunohistochemistry shows ACE2 protein predominantly in the endothelium of coronary and intrarenal vessels and in renal tubular epithelium. Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. ACE2 can also cleave des-arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested. ACE2 is not inhibited by lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney. The full text of this article is available at http://www.circresaha.org.