Species differences in angiotensin II generation and degradation by mast cell chymases.
Although chymases are known to exhibit species differences in regard to angiotensin (Ang) II generation and degradation, their properties have never been compared under the same experimental conditions. We analyzed the processing of Ang I by chymases of a variety of species (human chymase, dog chymase, hamster chymase-1, rat mast cell protease-1 [rMCP-1], mouse mast cell protease-4 [mMCP-4]) at physiological ionic strength and under neutral pH conditions. Human chymase generated Ang II from Ang I without further degradation, whereas the chymases of other species generated Ang II, followed by degradation at the Tyr4-Ile5 site in a time-dependent manner. Kinetic analysis showed that in terms of Ang II generating activity (analyzed by cleavage of the Phe8-His9 bond using the model peptide Ang(5-10), Ile5-His6-Pro7-Phe8-His9-Leu10), the chymases ranked as follows: dog > human > hamster > mouse > rat (kcat/Km: 18, 11, 0.69, 0.059, 0.030 microM-1min-1), and that in terms of Ang II degrading activity (i.e., cleavage of the Tyr4-Ile5 bond of Ang II), the order was hamster > rat > mouse > dog (kcat/Km: 5.4, 4.8, 0.39, 0.29 microM-lmin-1). These results suggest species differences in the contribution of chymases to local Ang II generation and degradation.
Kunori
Yuichi
Y
TEIJIN Institute for Biomedical Research, Hino, Tokyo, Japan. y.kunori@teijin.co.jp
Muroga
Yumiko
Y
Iidaka
Minako
M
Mitsuhashi
Hiroaki
H
Kamimura
Takashi
T
Fukamizu
Akiyoshi
A
D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D053818:Chymases; D006224:Cricetinae; D004285:Dogs; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*; D013045:Species Specificity
D000804:Angiotensin II; C509227:Cma1 protein, mouse; D012697:Serine Endopeptidases; C066932:mast cell protease 4; C509226:CMA1 protein, human; D053818:Chymases; C509228:Cma1 protein, rat; C509230:Mcpt1 protein, mouse; C509231:Mcpt1 protein, rat