Comparative studies on species-specific reactivity between renin and angiotensinogen

Autor: Akiyoshi Fukamizu, Toshihisa Hatae, Eriko Takimoto, Kazuo Murakami
Rok vydání: 1994
Předmět:
Zdroj: Molecular and Cellular Biochemistry. 131:43-47
ISSN: 1573-4919
0300-8177
Popis: The renin-angiotensin system (RAS) is the most important regulator of electrolyte homeostasis and blood pressure. Our recently generated transgenic mice carrying either the human renin (hREN) or human angiotensinogen (hANG) genes did not develop hypertension but dual gene strains obtained by cross-mating separate lines of mice exhibited a chronically sustained increase in blood pressure, suggesting the presence of species-specific reactivity between renin and angiotensinogen. In order to examine this specificity, the present study was designed to perform a strictly comparative study on hydrolysis of hANG by hREN and mouse submandibular renin (mREN) in vitro by using pure proteins. The recombinant hANG (rhANG) and the synthetic human-type tridecapeptide (hTDP), Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His, corresponding to the N-terminal sequences of hANG, were used to determine the species specificity of recombinant hREN (rhREN) and mREN. While hTDP was cleaved by both rhREN and mREN with similar Km and with the same order of kcat, rhANG was cleaved by mREN with 16.7-fold higher Km and with 28.2-fold lower kcat than by rhREN. These results showed that kcat/Km value of mREN for rhANG was 468-fold lower than that for rhREN acting on rhANG.
Databáze: OpenAIRE
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