Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis

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dc.contributor.authorMaroto, Marcos
dc.contributor.authorDiego, Antonio M. G. de
dc.contributor.authorAlbinana, Elisa
dc.contributor.authorFernandez-Morales, Jose C.
dc.contributor.authorCaricati-Neto, Afonso [UNIFESP]
dc.contributor.authorJurkiewicz, Aron [UNIFESP]
dc.contributor.authorYanez, Matilde
dc.contributor.authorIsabel Rodriguez-Franco, Maria
dc.contributor.authorConde, Santiago
dc.contributor.authorArce, Mariana P.
dc.contributor.authorHernandez-Guijo, Jesus M.
dc.contributor.authorGarcia, Antonio G.
dc.contributor.institutionUniv Autonoma Madrid
dc.contributor.institutionCSIC
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Santiago de Compostela
dc.date.accessioned2016-01-24T14:17:16Z
dc.date.available2016-01-24T14:17:16Z
dc.date.issued2011-10-01
dc.description.abstractCompound ITH33/IQM9.21 (ITH/IQM) belongs to a new family of L-glutamic acid derivatives with antioxidant and neuroprotective properties on in vitro and in vivo models of stroke. Because neuronal damage after brain ischemia is tightly linked to excess Ca2+ entry and neuronal Ca2+ overload, we have investigated whether compound ITH/IQM antagonises the elevations of the cytosolic Ca2+ concentrations ([Ca2+](c)) and the ensuing exocytotic responses triggered by depolarisation of bovine chromaffin cells. in fluo-4-loaded cell populations, ITH/IQM reduced the K+-evoked [Ca2+](c) transients with an IC50 of 5.31 mu M. At 10 mu M, the compound decreased the amplitude and area of the Ca2+ transient elicited by challenging single fura-2-loaded cells with high K+ by 40% and 80%, respectively. This concentration also caused a blockade of K+-induced catecholamine release at the single-cell level (78%) and cell populations (55%). These effects are likely due to blockade of the whole-cell inward Ca2+ currents (IC50 = 6.52 mu M). At 10 mu M, ITH/IQM also inhibited the Ca2+-dependent outward K+ current, leaving untouched the voltage-dependent component of I-K. the inward Na+ current was unaffected. Inhibition of depolarisation-elicited Ca2+ entry, [Ca2+](c) elevation and exocytosis could contribute to the neuroprotective effects of ITH/IQM in vulnerable neurons undergoing depolarisation during brain ischemia. (C) 2011 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Autonoma Madrid, Fac Med, Inst Teofilo Hernando, E-28029 Madrid, Spain
dc.description.affiliationUniv Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, E-28029 Madrid, Spain
dc.description.affiliationCSIC, Inst Quim Med, E-28006 Madrid, Spain
dc.description.affiliationUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUniv Santiago de Compostela, Fac Farm, Dept Farmacol, Santiago de Compostela, Spain
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Farmacol, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConsolider Program Ingenio-2010
dc.description.sponsorshipMinisterio de Ciencia e Innovacion, Spain
dc.description.sponsorshipInstituto de Salud Carlos III, Fundacion CIEN Ministerio de Ciencia e Innovacion, Spain
dc.description.sponsorshipComunidad Autonoma de Madrid, Spain
dc.description.sponsorshipAgencia Lain Entralgo, Madrid, Spain
dc.description.sponsorshipUAM-CEAL-Banco Santander
dc.description.sponsorshipIDConsolider Program Ingenio-2010: SAF 2006-03589
dc.description.sponsorshipIDMinisterio de Ciencia e Innovacion, Spain: SAF 2010-21795
dc.description.sponsorshipIDMinisterio de Ciencia e Innovacion, Spain: SAF 2006/01249
dc.description.sponsorshipIDMinisterio de Ciencia e Innovacion, Spain: SAF 2009-13015-C02-01
dc.description.sponsorshipIDInstituto de Salud Carlos III, Fundacion CIEN Ministerio de Ciencia e Innovacion, Spain: PIO 16/09
dc.description.sponsorshipIDComunidad Autonoma de Madrid, Spain: SAL2006/02751
dc.description.sponsorshipIDAgencia Lain Entralgo, Madrid, Spain: NDE 07/09
dc.format.extent359-369
dc.identifierhttp://dx.doi.org/10.1016/j.ceca.2011.06.006
dc.identifier.citationCell Calcium. Edinburgh: Churchill Livingstone, v. 50, n. 4, p. 359-369, 2011.
dc.identifier.doi10.1016/j.ceca.2011.06.006
dc.identifier.issn0143-4160
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34103
dc.identifier.wosWOS:000296683800005
dc.language.isoeng
dc.publisherChurchill Livingstone
dc.relation.ispartofCell Calcium
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectITH33/IQM9.21en
dc.subjectCalcium channelsen
dc.subjectCalcium-dependent potassium channelsen
dc.subjectCalcium signallingen
dc.subjectExocytosisen
dc.titleMulti-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosisen
dc.typeinfo:eu-repo/semantics/article
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