Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling

Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling

Author Guimarães, Paola Bianchi Autor UNIFESP Google Scholar
Alvarenga, Erika Costa Autor UNIFESP Google Scholar
Siqueira, Paula D. Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Sabatini, Regiane Angelica Autor UNIFESP Google Scholar
Morais, Rafael Leite Tavares de Autor UNIFESP Google Scholar
Reis, Rosana I. Google Scholar
Santos, Edson L. Google Scholar
Teixeira, Luis Gustavo de Deus Autor UNIFESP Google Scholar
Casarini, Dulce Elena Autor UNIFESP Google Scholar
Martin, Renan Paulo Autor UNIFESP Google Scholar
Shimuta, Suma Imura Autor UNIFESP Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Nakaie, Clovis Ryuichi Autor UNIFESP Google Scholar
Jasiulionis, Miriam Galvonas Autor UNIFESP Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Pesquero, Jorge L. Google Scholar
Oliveira, Suzana M. Autor UNIFESP Google Scholar
Bader, Michael Autor UNIFESP Google Scholar
Costa-Neto, Claudio M. Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Fundacao Univ Fed Grande Dourados
Max Delbruck Ctr Mol Med
Abstract Angiotensin (Ang) I-converting enzyme (ACE) is involved in the control of blood pressure by catalyzing the conversion of Ang I into the vasoconstrictor Ang II and degrading the vasodilator peptide bradykinin. Human ACE also functions as a signal transduction molecule, and the binding of ACE substrates or its inhibitors initiates a series of events. in this study, we examined whether Ang II could bind to ACE generating calcium signaling. Chinese hamster ovary cells transfected with an ACE expression vector reveal that Ang II is able to bind with high affinity to ACE in the absence of the Ang II type 1 and type 2 receptors and to activate intracellular signaling pathways, such as inositol 1,4,5-trisphosphate and calcium. These effects could be blocked by the ACE inhibitor, lisinopril. Calcium mobilization was specific for Ang II, because other ACE substrates or products, namely Ang 1-7, bradykinin, bradykinin 1-5, and N-acetyl-seryl-aspartyl-lysyl-proline, did not trigger this signaling pathway. Moreover, in Tm5, a mouse melanoma cell line endogenously expressing ACE but not Ang II type 1 or type 2 receptors, Ang II increased intracellular calcium and reactive oxygen species. in conclusion, we describe for the first time that Ang II can interact with ACE and evoke calcium and other signaling molecules in cells expressing only ACE. These findings uncover a new mechanism of Ang II action and have implications for the understanding of the renin-Ang system. (Hypertension. 2011;57:965-972.) . Online Data Supplement
Keywords angiotensin I-converting enzyme
ACE
calcium
angiotensin
cells
receptors
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Deutsche Akademische Austauchdienst Probral
Grant number FAPESP: 02/00807-7
CNPq: 520012/02-0
Date 2011-05-01
Published in Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 57, n. 5, p. 965-U200, 2011.
ISSN 0194-911X (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 965-U200
Origin http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167171
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000289730200024
URI http://repositorio.unifesp.br/handle/11600/33657

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