000063444 001__ 63444
000063444 005__ 20210121114523.0
000063444 0247_ $$2doi$$a10.1371/journal.pone.0118148
000063444 0248_ $$2sideral$$a103187
000063444 037__ $$aART-2015-103187
000063444 041__ $$aeng
000063444 100__ $$aFernández-Mariño, A.I.
000063444 245__ $$aTungstate-targeting of BKaß1 channels tunes ERK phosphorylation and cell proliferation in human vascular smooth muscle
000063444 260__ $$c2015
000063444 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063444 5203_ $$aDespite 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 BKaß1 potassium channel, which modulates vascular smooth muscle cell (VSMC) proliferation and function, respectively. Here, we have assessed the possible involvement of BKaß1 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 BKaß1 channels potentiates the tungstate-induced ERK1/2 phosphorylation in a Gi/o protein-dependent manner. Tungstate activated BKaß1 channels upstream of G proteins as channel activation was not altered by the inhibition of G proteins with GDPßS or pertussis toxin. Moreover, analysis of Gi/o protein activation measuring the FRET among heterologously expressed Gi protein subunits suggested that tungstate-targeting of BKaß1 channels promotes G protein activation. Single channel recordings on VSMCs from wild-type and ß1-knockout mice indicated that the presence of the regulatory ß1 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 BKaß1 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.
000063444 536__ $$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2012-38140$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/SAF2012-31089$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-45867-R$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-15898$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2008-00769$$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0014$$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0042-0006$$9info:eu-repo/grantAgreement/EC/FP7/321721/EU/Identification and validation of cerebral KCa3.1/KCa2.3 potassium channels a drug tragets for the prevention and treatment of cerebral ischemia associated with diabetes and Alzheimers disease/BRAINIK
000063444 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063444 590__ $$a3.057$$b2015
000063444 591__ $$aMULTIDISCIPLINARY SCIENCES$$b11 / 62 = 0.177$$c2015$$dQ1$$eT1
000063444 592__ $$a1.427$$b2015
000063444 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2015$$dQ1
000063444 593__ $$aMedicine (miscellaneous)$$c2015$$dQ1
000063444 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000063444 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063444 700__ $$aCidad, P.
000063444 700__ $$aZafra, D.
000063444 700__ $$aNocito, L.
000063444 700__ $$aDomínguez, J.
000063444 700__ $$0(orcid)0000-0001-5348-924X$$aOliván-Viguera, A.
000063444 700__ $$aKöhler, R.
000063444 700__ $$aLópez-López, J.R.
000063444 700__ $$aPérez-García, M.T.
000063444 700__ $$aValverde, M.Á.
000063444 700__ $$aGuinovart, J.J.
000063444 700__ $$aFernández-Fernández, J.M.
000063444 773__ $$g10, 2 (2015), e0118148[21 pp]$$pPLoS One$$tPloS one$$x1932-6203
000063444 8564_ $$s1120481$$uhttps://zaguan.unizar.es/record/63444/files/texto_completo.pdf$$yVersión publicada
000063444 8564_ $$s111237$$uhttps://zaguan.unizar.es/record/63444/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063444 909CO $$ooai:zaguan.unizar.es:63444$$particulos$$pdriver
000063444 951__ $$a2021-01-21-11:04:45
000063444 980__ $$aARTICLE