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dc.contributor.authorArroba, Ana I.-
dc.contributor.authorWallace, Deborah-
dc.contributor.authorMackey, Ashley-
dc.contributor.authorDe la Rosa, Enrique J.-
dc.contributor.authorCotter, Thomas G.-
dc.identifier.citationEuropean Journal of Neuroscience 30(6):975-986(2009)es_ES
dc.description12 pági,as 13 figuras, 1 tabla -- PAGS nros. 975-986es_ES
dc.description.abstractRetinitis pigmentosa is a heterogeneous group of inherited retinal dystrophies in which the loss of photoreceptor cells via apoptosis leads to blindness. In this study we have experimentally mimicked this condition by treating 661W cells and wild-type mouse retinal explants with a Ca2+ ionophore. Ca2+ overload induced apoptosis, which was correlated with calpain-2 activation, loss of calpastatin, its endogenous inhibitor, as well as the loss of its transcriptional activator, phospho-cAMP response element binding (CREB). All are similar changes to those observed in the rd1 mouse model of retinitis pigmentosa. Insulin like-growth factor-I (IGF-I) attenuated this Ca2+-induced apoptosis, as well as decreased the activation of calpain-2 and maintained calpastatin levels through the activation of the Akt-CREB pathway. Similarly, IGF-I decreased photoreceptor apoptosis in rd1 mouse retinal explants in parallel with reduced activation of calpain-2 and increased levels of calpastatin and activation of phospho-CREB. In conclusion, IGF-I seems to protect neural cells following a physiopathological or an experimental increase in intracellular Ca2+, an observation that may have therapeutic consequences in neurodegenerative diseases such as retinitis pigmentosaes_ES
dc.description.sponsorshipThis work was supported by Science Foundation Ireland (T.G.C.), the Spanish Ministerio de Ciencia e Innovación (SAF2007-66175, E.J.dlR.), the Fundación Médica Mutua Madrileña (E.J.dlR.) and Fundaluce (E.J.dlR.). A.I.A. is a postdoctoral fellow financed by the Fondo de Investigaciones Sanitarias (Spain)es_ES
dc.publisherBlackwell Publishinges_ES
dc.subjectCa2+-induced apoptosises_ES
dc.subjectrd1 mousees_ES
dc.subjectretinitis pigmentosaes_ES
dc.titleIGF-I maintains calpastatin expression and attenuates apoptosis in several models of photoreceptor cell deathes_ES
dc.description.peerreviewedPeer reviewedes_ES
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