Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
dARK ID: | ark:/48912/001300000j8q0 |
Texto Completo: | http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167171 http://repositorio.unifesp.br/handle/11600/33657 |
Resumo: | 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 |
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Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signalingangiotensin I-converting enzymeACEcalciumangiotensincellsreceptorsAngiotensin (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 SupplementUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, São Paulo, BrazilFundacao Univ Fed Grande Dourados, Fac Ciencias Biol & Ambientais, Mato Grosso, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyUniversidade Federal de São Paulo, Dept Biofis, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilWeb of ScienceFundação 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 ProbralFAPESP: 02/00807-7CNPq: 520012/02-0Lippincott Williams & WilkinsUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Fundacao Univ Fed Grande DouradosMax Delbruck Ctr Mol MedGuimarães, Paola Bianchi [UNIFESP]Alvarenga, Erika Costa [UNIFESP]Siqueira, Paula D. [UNIFESP]Paredes-Gamero, Edgar Julian [UNIFESP]Sabatini, Regiane Angelica [UNIFESP]Morais, Rafael Leite Tavares de [UNIFESP]Reis, Rosana I.Santos, Edson L.Teixeira, Luis Gustavo de Deus [UNIFESP]Casarini, Dulce Elena [UNIFESP]Martin, Renan Paulo [UNIFESP]Shimuta, Suma Imura [UNIFESP]Carmona, Adriana Karaoglanovic [UNIFESP]Nakaie, Clovis Ryuichi [UNIFESP]Jasiulionis, Miriam Galvonas [UNIFESP]Ferreira, Alice Teixeira [UNIFESP]Pesquero, Jorge L.Oliveira, Suzana M. [UNIFESP]Bader, Michael [UNIFESP]Costa-Neto, Claudio M.Pesquero, João Bosco [UNIFESP]2016-01-24T14:16:40Z2016-01-24T14:16:40Z2011-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion965-U200http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167171Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 57, n. 5, p. 965-U200, 2011.10.1161/HYPERTENSIONAHA.110.1671710194-911Xhttp://repositorio.unifesp.br/handle/11600/33657WOS:000289730200024ark:/48912/001300000j8q0engHypertensioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2023-05-18T14:58:10Zoai:repositorio.unifesp.br/:11600/33657Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:20:52.529949Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
title |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
spellingShingle |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling Guimarães, Paola Bianchi [UNIFESP] angiotensin I-converting enzyme ACE calcium angiotensin cells receptors |
title_short |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
title_full |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
title_fullStr |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
title_full_unstemmed |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
title_sort |
Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling |
author |
Guimarães, Paola Bianchi [UNIFESP] |
author_facet |
Guimarães, Paola Bianchi [UNIFESP] Alvarenga, Erika Costa [UNIFESP] Siqueira, Paula D. [UNIFESP] Paredes-Gamero, Edgar Julian [UNIFESP] Sabatini, Regiane Angelica [UNIFESP] Morais, Rafael Leite Tavares de [UNIFESP] Reis, Rosana I. Santos, Edson L. Teixeira, Luis Gustavo de Deus [UNIFESP] Casarini, Dulce Elena [UNIFESP] Martin, Renan Paulo [UNIFESP] Shimuta, Suma Imura [UNIFESP] Carmona, Adriana Karaoglanovic [UNIFESP] Nakaie, Clovis Ryuichi [UNIFESP] Jasiulionis, Miriam Galvonas [UNIFESP] Ferreira, Alice Teixeira [UNIFESP] Pesquero, Jorge L. Oliveira, Suzana M. [UNIFESP] Bader, Michael [UNIFESP] Costa-Neto, Claudio M. Pesquero, João Bosco [UNIFESP] |
author_role |
author |
author2 |
Alvarenga, Erika Costa [UNIFESP] Siqueira, Paula D. [UNIFESP] Paredes-Gamero, Edgar Julian [UNIFESP] Sabatini, Regiane Angelica [UNIFESP] Morais, Rafael Leite Tavares de [UNIFESP] Reis, Rosana I. Santos, Edson L. Teixeira, Luis Gustavo de Deus [UNIFESP] Casarini, Dulce Elena [UNIFESP] Martin, Renan Paulo [UNIFESP] Shimuta, Suma Imura [UNIFESP] Carmona, Adriana Karaoglanovic [UNIFESP] Nakaie, Clovis Ryuichi [UNIFESP] Jasiulionis, Miriam Galvonas [UNIFESP] Ferreira, Alice Teixeira [UNIFESP] Pesquero, Jorge L. Oliveira, Suzana M. [UNIFESP] Bader, Michael [UNIFESP] Costa-Neto, Claudio M. Pesquero, João Bosco [UNIFESP] |
author2_role |
author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) Fundacao Univ Fed Grande Dourados Max Delbruck Ctr Mol Med |
dc.contributor.author.fl_str_mv |
Guimarães, Paola Bianchi [UNIFESP] Alvarenga, Erika Costa [UNIFESP] Siqueira, Paula D. [UNIFESP] Paredes-Gamero, Edgar Julian [UNIFESP] Sabatini, Regiane Angelica [UNIFESP] Morais, Rafael Leite Tavares de [UNIFESP] Reis, Rosana I. Santos, Edson L. Teixeira, Luis Gustavo de Deus [UNIFESP] Casarini, Dulce Elena [UNIFESP] Martin, Renan Paulo [UNIFESP] Shimuta, Suma Imura [UNIFESP] Carmona, Adriana Karaoglanovic [UNIFESP] Nakaie, Clovis Ryuichi [UNIFESP] Jasiulionis, Miriam Galvonas [UNIFESP] Ferreira, Alice Teixeira [UNIFESP] Pesquero, Jorge L. Oliveira, Suzana M. [UNIFESP] Bader, Michael [UNIFESP] Costa-Neto, Claudio M. Pesquero, João Bosco [UNIFESP] |
dc.subject.por.fl_str_mv |
angiotensin I-converting enzyme ACE calcium angiotensin cells receptors |
topic |
angiotensin I-converting enzyme ACE calcium angiotensin cells receptors |
description |
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 |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-05-01 2016-01-24T14:16:40Z 2016-01-24T14:16:40Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167171 Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 57, n. 5, p. 965-U200, 2011. 10.1161/HYPERTENSIONAHA.110.167171 0194-911X http://repositorio.unifesp.br/handle/11600/33657 WOS:000289730200024 |
dc.identifier.dark.fl_str_mv |
ark:/48912/001300000j8q0 |
url |
http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.167171 http://repositorio.unifesp.br/handle/11600/33657 |
identifier_str_mv |
Hypertension. Philadelphia: Lippincott Williams & Wilkins, v. 57, n. 5, p. 965-U200, 2011. 10.1161/HYPERTENSIONAHA.110.167171 0194-911X WOS:000289730200024 ark:/48912/001300000j8q0 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hypertension |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
965-U200 |
dc.publisher.none.fl_str_mv |
Lippincott Williams & Wilkins |
publisher.none.fl_str_mv |
Lippincott Williams & Wilkins |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1818602471760592896 |