PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition

[Background/Aims] Protein kinase C (PKC)- and RhoA/Rho-associated kinase (ROCK) play important roles in arterial sustained contraction. Although depolarization-elicited RhoA/ROCK activation is accepted, the role of PKC in depolarized vascular smooth muscle cells (VSMCs) is a subject of controversy....

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Autores: González-Montelongo, María del Carmen, Porras-González, Cristina, González-Montelongo, Rafaela, Revilla-González, Gonzalo, Pastor, María Dolores, Castellano, Antonio, Ureña, Juan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/203276
Acceso en línea:http://hdl.handle.net/10261/203276
Access Level:acceso abierto
Palabra clave:Protein kinase C (PKC)
Rho (Rho GTPase)
Vascular smooth muscle cells
Calcium channels
Cell signalling
Phorbol ester
Depolarization
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spelling PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK InhibitionGonzález-Montelongo, María del CarmenPorras-González, CristinaGonzález-Montelongo, RafaelaRevilla-González, GonzaloPastor, María DoloresCastellano, AntonioUreña, JuanProtein kinase C (PKC)Rho (Rho GTPase)Vascular smooth muscle cellsCalcium channelsCell signallingPhorbol esterDepolarization[Background/Aims] Protein kinase C (PKC)- and RhoA/Rho-associated kinase (ROCK) play important roles in arterial sustained contraction. Although depolarization-elicited RhoA/ROCK activation is accepted, the role of PKC in depolarized vascular smooth muscle cells (VSMCs) is a subject of controversy. Our aim was to study the role of PKC in arterial contraction and its interaction with RhoA/ROCK.[Methods] Mass spectrometry was used to identify the PKC isoenzymes. PKCα levels and RhoA activity were analyzed by western blot and G-LISA, respectively, and isometric force was measured in arterial rings.[Results] In depolarized VSMCs RhoA and PKCα were translocated to the plasma membrane, where they colocalize and coimmunoprecipitate. Interestingly, depolarization-induced RhoA activation was downregulated by PKCα, effect reverted by PKCα inhibition. Phorbol 12,13-dibutyrate (PDBu) induced the translocation of PKCα to the plasma membrane, increased the level of RhoA in the cytosol and reduced RhoA/ROCK activity. These effects were reverted when PKC was inhibited. Pharmacological or siRNA inhibition of PKCα synergistically potentiated the vasorelaxant effect of RhoA/ROCK inhibition.[Conclusion] The present study provides the first evidence that RhoA activity is downregulated by PKCα in depolarized and PDBu treated freshly isolated VSMCs and arteries, with an important physiological role on arterial contractility.This work was supported by the "Red de Investigación Cardiovascular, RIC, RD12/0042/0041" of the Instituto de Salud Carlos III and by Ministerio de Economía y Competitividad and FEDER (SAF2013-46806-R and SAF2017-89474-R). WPeer reviewedS. Karger AGRed de Investigación Cardiovascular (España)Instituto de Salud Carlos IIIEuropean CommissionMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/203276reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-46806-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-89474-Rhttp://dx.doi.org/10.33594/000000006Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2032762026-05-22T06:33:51Z
dc.title.none.fl_str_mv PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
title PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
spellingShingle PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
González-Montelongo, María del Carmen
Protein kinase C (PKC)
Rho (Rho GTPase)
Vascular smooth muscle cells
Calcium channels
Cell signalling
Phorbol ester
Depolarization
title_short PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
title_full PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
title_fullStr PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
title_full_unstemmed PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
title_sort PKCα-Mediated Downregulation of RhoA Activity in Depolarized Vascular Smooth Muscle: Synergistic Vasorelaxant Effect of PKCα and ROCK Inhibition
dc.creator.none.fl_str_mv González-Montelongo, María del Carmen
Porras-González, Cristina
González-Montelongo, Rafaela
Revilla-González, Gonzalo
Pastor, María Dolores
Castellano, Antonio
Ureña, Juan
author González-Montelongo, María del Carmen
author_facet González-Montelongo, María del Carmen
Porras-González, Cristina
González-Montelongo, Rafaela
Revilla-González, Gonzalo
Pastor, María Dolores
Castellano, Antonio
Ureña, Juan
author_role author
author2 Porras-González, Cristina
González-Montelongo, Rafaela
Revilla-González, Gonzalo
Pastor, María Dolores
Castellano, Antonio
Ureña, Juan
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Red de Investigación Cardiovascular (España)
Instituto de Salud Carlos III
European Commission
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Protein kinase C (PKC)
Rho (Rho GTPase)
Vascular smooth muscle cells
Calcium channels
Cell signalling
Phorbol ester
Depolarization
topic Protein kinase C (PKC)
Rho (Rho GTPase)
Vascular smooth muscle cells
Calcium channels
Cell signalling
Phorbol ester
Depolarization
description [Background/Aims] Protein kinase C (PKC)- and RhoA/Rho-associated kinase (ROCK) play important roles in arterial sustained contraction. Although depolarization-elicited RhoA/ROCK activation is accepted, the role of PKC in depolarized vascular smooth muscle cells (VSMCs) is a subject of controversy. Our aim was to study the role of PKC in arterial contraction and its interaction with RhoA/ROCK.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/203276
url http://hdl.handle.net/10261/203276
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-46806-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-89474-R
http://dx.doi.org/10.33594/000000006
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv S. Karger AG
publisher.none.fl_str_mv S. Karger AG
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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