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dc.contributor.authorLópez López, José Ramón 
dc.contributor.authorFernández Mariño, Ana Isabel
dc.contributor.authorCidad Velasco, María del Pilar
dc.contributor.authorZafra, Delia
dc.contributor.authorNocito, Laura
dc.contributor.authorDomínguez, Jorge
dc.contributor.authorOliván Viguera, Aida
dc.contributor.authorKöhler, Ralf
dc.contributor.authorPérez García, María Teresa 
dc.contributor.authorValverde, Miguel Ángel
dc.contributor.authorGuinovart, Joan J.
dc.contributor.authorFernández Fernández, José Manuel
dc.date.accessioned2018-03-23T12:45:02Z
dc.date.available2018-03-23T12:45:02Z
dc.date.issued2015
dc.identifier.citationPlos One, 2015, p. 1-21es
dc.identifier.issn1932-6203es
dc.identifier.urihttp://uvadoc.uva.es/handle/10324/29191
dc.descriptionProducción Científicaes
dc.description.abstractDespite the substantial knowledge on the antidiabetic, antiobesity and antihypertensive actions of tungstate, information on its primary target/s is scarce. Tungstate activates both the ERK1/2 pathway and the vascular voltage- and Ca2+-dependent large-conductance BKαβ1 potassium channel, which modulates vascular smooth muscle cell (VSMC) proliferation and function, respectively. Here, we have assessed the possible involvement of BKαβ1 channels in the tungstate-induced ERK phosphorylation and its relevance for VSMC proliferation. Western blot analysis in HEK cell lines showed that expression of vascular BKαβ1 channels potentiates the tungstate-induced ERK1/2 phosphorylation in a Gi/o protein-dependent manner. Tungstate activated BKαβ1 channels upstream of G proteins as channel activation was not altered by the inhibition of G proteins with GDPβS or pertussis toxin. Moreover, analysis of Gi/o protein activation measuring the FRET among heterologously expressed Gi protein subunits suggested that tungstate-targeting of BKαβ1 channels promotes G protein activation. Single channel recordings on VSMCs from wild-type and β1-knockout mice indicated that the presence of the regulatory β1 subunit was essential for the tungstate-mediated activation of BK channels in VSMCs. Moreover, the specific BK channel blocker iberiotoxin lowered tungstate-induced ERK phosphorylation by 55% and partially reverted (by 51%) the tungstate-produced reduction of platelet-derived growth factor (PDGF)-induced proliferation in human VSMCs. Our observations indicate that tungstate-targeting of BKαβ1 channels promotes activation of PTX-sensitive Gi proteins to enhance the tungstate-induced phosphorylation of ERK, and inhibits PDGF-stimulated cell proliferation in human vascular smooth muscle.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherPloses
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.classificationCalcioes
dc.subject.classificationMetabolismoes
dc.titleTungstate-Targeting of BKαβ1 Channels Tunes ERK Phosphorylation and Cell Proliferation in Human Vascular Smooth Musclees
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0118148es
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118148es
dc.identifier.publicationfirstpage1es
dc.identifier.publicationlastpage21es
dc.peerreviewedSIes
dc.description.projectMinisterio de Economía, Industria y Competitividad (SAF2012-31089 to JMFF, SAF2012-38140 to MAV, BFU2013-45867-R to JRLL)es
dc.description.projectMinisterio de Ciencia e Innovación (BFU 2008-00769 to JG, BFU2010-15898 to MTPG)
dc.description.projectInstituto de Salud Carlos III (RIC RD12/0042/0006, RD12/0042/0014, Red HERACLES)
dc.description.projectJunta de Castilla y León (VA094A11-2 to JRLL)
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/CIG-321721
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International


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