A memorial to Robert Tiegerstedt - The centennial of renin discovery

A memorial to Robert Tiegerstedt - The centennial of renin discovery
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DOI:
10.1161/01.hyp.32.6.953
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发表时间:
1998-12-01
期刊:
影响因子:
8.3
通讯作者:
Inagami, T
Inagami, T
中科院分区:
医学1区
文献类型:
--
作者:
Inagami, T

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血管紧张素原没有一般的蛋白质消化活性,因此满足了对特异性肽酶生成酶的要求。[7]一种特异性肽酶的发现也是一个重要的发现,后来在许多其他机制中找到了支持,这些机制从它们的激素原产生肽激素,这些激素原由一种专门用于每种激素原的特异性肽酶介导。Murakami和Brundell的研究小组用分子诱变和X射线晶体学研究了这种独特底物特异性的分子机制(综述见参考文献6)。纯化的肾素使我们和Hackenthal能够产生定义明确的肾素单特异性抗体。使用这些抗体,我们和Hackenthal的小组能够产生明确的证据表明肾小球细胞中的致密颗粒含有肾素,支持Goormaghtigh和Dunihue的早期假设。此外,这些细胞和垂体和睾丸中的其他含肾素细胞也被发现含有Ang II,表明可能通过肾素在细胞内产生Ang II(参见参考文献8的综述)。
angiotensinogen without a general protein digestive activity, thus fulfilling the requirement for a specific peptide hormone–generating enzyme. 7 The finding of a hormonespecific peptidase was also an important discovery that later found support in many other mechanisms generating peptide hormone from their prohormones, which are mediated by a specific peptidase dedicated for each prohormone. The molecular mechanism for the unique substrate specificity was investigated by Murakami and Brundell’s group with molecular mutagenesis and x-ray crystallographic studies (see Reference 6 for review).Purified renin allowed us and Hackenthal to produce well-defined monospecific antibodies to renin. Using these antibodies, we and Hackenthal’s group were able to produce definitive evidence that the dense granules in juxtaglomerular cells contain renin, supporting the earlier hypotheses by Goormaghtigh and Dunihue. Furthermore, these cells and other renin-containing cells in pituitary and testis were also found to contain Ang II, indicating possible intracellular generation of Ang II by renin (see Reference 8 for review).