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dc.contributor.authorMontero, M.
dc.contributor.authorDomínguez Lobatón, María Carmen 
dc.contributor.authorGutierrez-Fernández, S.
dc.contributor.authorMoreno, A.
dc.contributor.authorÁlvarez Martín, Javier 
dc.date.accessioned2014-09-15T16:33:52Z
dc.date.available2015-09-15T23:40:09Z
dc.date.issued2004
dc.identifier.citationBritish Journal of Pharmacology, 2004, vol. 141, n. 2, p. 263-268es
dc.identifier.issn0007-1188es
dc.identifier.urihttp://uvadoc.uva.es/handle/10324/5956
dc.descriptionProducción Científicaes
dc.description.abstractCyclosporin A (CsA) is a widely used compound because ofits potent immunosupressive properties, derived mainly from the inhibition of calcineurin, and also because of its ability to block the mitochondrial permeability transition pore (PTP). This second effect has been involved in the protection against apoptosis mediated by release ofmitochondrial factors. We show here that CsA (1– 10mM) has an additional effect on Ca2+ homeostasis in mitochondria that cannot be attributed to inhibition ofPTP. By measuring specifically mitochondrial [Ca2+] with targeted aequorin, we show that CsA inhibited Ca2+ entry into mitochondria both in intact and in permeabilized cells, and this effect was stronger when Ca2+ entry was triggered by low cytosolic [Ca2+], below 5 mM. Inhibition ofmitochondrial Ca2+ uptake required micromolar concentrations ofCsA and was not mimicked by other inhibitors of calcineurin such as FK-506 or cypermethrin, nor by a different inhibitor ofthe PTP, bongkrekic acid. CsA blocked the increase in mitochondrial Ca2+ uptake rate induced by the mitochondrial Ca2+ uniporter activator SB202190. 5 Our results suggest that CsA inhibits Ca2+ entry through the Ca2+ uniporter by a mechanism independent ofthe inhibition ofPTP or calcineurin. This effect may contribute to reduce depolarization and Ca2+ overloading in mitochondria after cell stimulation, and thus cooperate with the direct inhibition ofPTP to prevent apoptosis.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherNature Publishing Groupes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCalcio - Metabolismoes
dc.titleCalcineurin-independent inhibition of mitochondrial Ca2+ uptake by cyclosporin Aes
dc.typeinfo:eu-repo/semantics/articlees
dc.identifier.doi10.1038/sj.bjp.0705609es
dc.identifier.publicationfirstpage263es
dc.identifier.publicationissue2es
dc.identifier.publicationlastpage268es
dc.identifier.publicationtitleBritish Journal of Pharmacologyes
dc.identifier.publicationvolume141es
dc.peerreviewedSIes
dc.description.embargo2015-09-15es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International


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