title: Characterization of the renal renin-angiotensin system in transgenic mice that express rat tonin.
abstract: BACKGROUND
  Tonin is an enzyme that is able to generate angiotensin II (Ang II) from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to characterize the renal renin-angiotensin system in transgenic mice that express rat tonin (TGM`(rTon)).
  
  
  METHODS
  Mice were euthanized and the kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and angiotensin II-converting enzyme (ACE2) expression was analyzed by Western blotting.
  
  
  RESULTS
  Tonin activity was significantly increased in TGM`(rTon) compared to their respective wild-type (WT) littermates (1.7 ± 0.21 vs 0.11 ± 0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive correlation with tonin expression in both TGM`(rTon) and their respective wild-type littermates. The ACE activity and expression levels of 65-kDa N-domain angiotensin I-converting enzyme isoform were significantly increased in the TGM`(rTon) when compared with WT. ACE2 expression levels were statistically significantly higher in the TGM`(rTon) when compared with WT. Angiotensin 1-7 (Ang(1-7)) and Ang I levels were significantly lower in the TGM`(rTon).
  
  
  CONCLUSIONS
  We suggest that the environment of tonin abundance may increase N-domain ACE activity liberated by a secretase able to cleave somatic ACE.
authors.affiliation: Department of Medicine, Nephrology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Ribeiro
authors.affiliation: Department of Medicine, Nephrology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
authors.forename: Zaira
authors.initials: Z
authors.lastname: Palomino
authors.affiliation: Department of Basic Nursing, Nursing School, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Mércia P
authors.initials: MP
authors.lastname: Lima
authors.affiliation: Heart Institute, Medical School of University of São Paulo, Brazil.
authors.forename: Leandro E
authors.initials: LE
authors.lastname: Souza
authors.affiliation: Department of Biophysics, Universidade Federal de São Paulo, Brazil.
authors.forename: Daniele S
authors.initials: DS
authors.lastname: Ferreira
authors.affiliation: Department of Biophysics, Universidade Federal de São Paulo, Brazil.
authors.forename: João B
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Heart Institute, Medical School of University of São Paulo, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Irigoyen
authors.affiliation: Department of Biophysics, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Pesquero
authors.affiliation: Department of Medicine, Nephrology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil casarini.elena@unifesp.br.
authors.forename: Dulce E
authors.initials: DE
authors.lastname: Casarini
mesh_terms: D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*; D013194:Staining and Labeling; D020840:Tissue Kallikreins / Q000378:metabolism*
chemical_list: D000809:Angiotensins; D007527:Isoenzymes; D007703:Peptidyl-Dipeptidase A; C117017:tonin; D020840:Tissue Kallikreins; D012083:Renin
keywords: N-domain ACE; Tonin; angiotensin II; renal renin angiotensin system; transgenic mice