title: Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme.
abstract: Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension.
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, Brazil.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Aragão
authors.affiliation: Albert Einstein Research Institute, Brazil.
authors.forename: Maria Claudina C
authors.initials: MC
authors.lastname: de Andrade
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Ebihara
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, Brazil.
authors.forename: Ingrid K M
authors.initials: IK
authors.lastname: Watanabe
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, Brazil.
authors.forename: Dayane C B P
authors.initials: DC
authors.lastname: Magalhães
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Juliano
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Brazil.
authors.forename: Izaura Yoshico
authors.initials: IY
authors.lastname: Hirata
authors.affiliation: Department of Medicine, Nephrology Division, Federal University of São Paulo, Brazil. Electronic address: casarini.elena@unifesp.br.
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000378:metabolism; D050527:Mesangial Cells / Q000201:enzymology / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D057057:Serine Proteases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D000804:Angiotensin II; D000803:Angiotensin I; D057057:Serine Proteases; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-I converting enzyme; Shedding, Mesangial cells