Mouse mast cell protease-1 cleaves angiotensin I to form angiotensin II.
The ability to convert angiotensin (Ang) I to Ang II was compared between human alpha-chymase and two mouse beta-chymases, mouse mast cell protease (mMCP)-1 and mMCP-4. Human chymase hydrolyzed Ang I to produce Ang II without further degradation. mMCP-1 similarly generated Ang II from Ang I in a time-dependent manner and the formation of the fragment other than Ang II was marginal. In contrast, mMCP-4 hydrolyzed Ang I at two sites, Tyr(4)-Ile(5) and Phe(8)-His(9), with Ang II formation being tentative. Consistently, mMCP-4 but not human chymase hydrolyzed Ang II and mMCP-1 showed little hydrolytic activity against Ang II. These data suggest that not only human chymase but also mMCP-1 might possess a physiological role in Ang II formation. Our findings also imply that the Ang-converting activity of chymase may not be related to the categorization of chymase into alpha- or beta-type based on their primary structure.
Saito
Kayo
K
Suntory Biomedical Research Limited, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
Muto
Tsuyoshi
T
Tomimori
Yoshiaki
Y
Imajo
Seiichi
S
Maruoka
Hiroshi
H
Tanaka
Taisaku
T
Yamashiro
Kyoko
K
Fukuda
Yoshiaki
Y
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D053818:Chymases; D006801:Humans; D051379:Mice; D012697:Serine Endopeptidases / Q000378:metabolism*
D000804:Angiotensin II; D000803:Angiotensin I; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D053818:Chymases; C509230:Mcpt1 protein, mouse