A scrutiny of the biochemical pathways from Ang II to Ang-(3-4) in renal basolateral membranes

A scrutiny of the biochemical pathways from Ang II to Ang-(3-4) in renal basolateral membranes

Author Axelband, Flavia Google Scholar
Dias, Juliana Google Scholar
Miranda, Filipe Google Scholar
Ferrao, Fernanda M. Google Scholar
Barros, Nilana M. Autor UNIFESP Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Lara, Lucienne S. Google Scholar
Vieyra, Adalberto Google Scholar
Institution Universidade Federal do Rio de Janeiro (UFRJ)
Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi
Universidade Federal de São Paulo (UNIFESP)
Abstract In a previous paper we demonstrated that Ang-(3-4) counteracts inhibition of the Ca(2+)-ATPase by Ang II in the basolateral membranes of kidney proximal tubules cells (BLM). We have now investigated the enzymatic routs by which Ang II is converted to Ang-(3-4). Membrane-bound angiotensin converting enzyme, aminopeptidases and neprilysin were identified using fluorescent substrates. HPLC showed that Plummer's inhibitor but not Z-pro-prolinal blocks Ang if metabolism, suggesting that carboxypeptidase N catalyzes the conversion Ang II -> Ang-(1-7). Different combinations of bestatin, thiorphan, Plummer's inhibitor, Ang II and Ang-(1-5), and use of short proteolysis times, indicate that Ang-(1-7)-> Ang-(1-5)-> Ang-(1-4)-> Ang-(3-4) is a major route. When Ang III was combined with the same inhibitors, the following pathway was demonstrated: Ang III -> Ang IV -> Ang-(3-4). Ca(2+)-ATPase assays with different Ang II concentrations and different peptidase inhibitors confirm the existence of these pathways in BLM and show that a prolylcarboxypeptidase may be an alternative catalyst for converting Ang II to Ang-(1-7). Overall, we demonstrated that BLM have all the peptidase machinery required to produce Ang-(3-4) in the vicinity of the Ca(2+)-ATPase, enabling a local RAS axis to effect rapid modulation of active Ca(2+) fluxes. (C) 2009 Elsevier B.V. All rights reserved.
Keywords Ang-(3-4)
Plasma membrane Ca(2+)-ATPase
Peptidases
Angiotensin metabolism
Kidney cells
Basolateral membranes
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Jose Bonifacio Foundation
Date 2009-11-27
Published in Regulatory Peptides. Amsterdam: Elsevier B.V., v. 158, n. 1-3, p. 47-56, 2009.
ISSN 0167-0115 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 47-56
Origin http://dx.doi.org/10.1016/j.regpep.2009.08.004
Access rights Closed access
Type Article
Web of Science ID WOS:000271556100008
URI http://repositorio.unifesp.br/handle/11600/31954

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