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Authordc.contributor.authorShaikh, S. 
Authordc.contributor.authorTroncoso Cotal, Rodrigo 
Authordc.contributor.authorMondaca Ruff, David 
Authordc.contributor.authorParra Ortíz, María Valentina 
Authordc.contributor.authorGarcía Nannig, Lorena 
Authordc.contributor.authorChiong Lay, Mario 
Authordc.contributor.authorLavandero González, Sergio
Admission datedc.date.accessioned2018-07-23T13:23:30Z
Available datedc.date.available2018-07-23T13:23:30Z
Publication datedc.date.issued2018
Cita de ítemdc.identifier.citationToxicology in Vitro, 48 (2018) 121–127es_ES
Identifierdc.identifier.other10.1016/j.tiv.2018.01.005
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/150122
Abstractdc.description.abstractStromal-interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in vivo. Moreover, there is growing support for the contribution of SOCE to the Ca2+ overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition is proposed as a novel target for controlling both hypertrophy and ischemia/reperfusion-induced Ca2+ overload. Our aim was to evaluate the effect of ML9, a STIM1 inhibitor, on cardiomyocyte viability. ML9 was found to induce cell death in cultured neonatal rat cardiomyocytes. Caspase-3 activation, apoptotic index and release of the necrosis marker lactate dehydrogenase to the extracellular medium were evaluated. ML9-induced cardiomyocyte death was not associated with increased intracellular ROS or decreased ATP levels. Moreover, treatment with ML9 significantly increased levels of the autophagy marker LC3-II, without altering Beclin1 or p62 protein levels. However, treatment with ML9 followed by bafilomycin-A1 did not produce further increases in LC3-II content. Furthermore, treatment with ML9 resulted in decreased LysoTracker (R) Green staining. Collectively, these data suggest that ML9-induced cardiomyocyte death is triggered by a ML9-dependent disruption of autophagic flux due to lysosomal dysfunction.es_ES
Patrocinadordc.description.sponsorshipFONDECYT, Chile 3150545 FONDAP 15130011es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherElsevieres_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Sourcedc.sourceToxicology in Vitroes_ES
Keywordsdc.subjectAutophagyes_ES
Keywordsdc.subjectCardiomyocyteses_ES
Keywordsdc.subjectCell deathes_ES
Keywordsdc.subjectLC3es_ES
Keywordsdc.subjectML9es_ES
Keywordsdc.subjectLysosomeses_ES
Títulodc.titleThe STIM1 inhibitor ML9 disrupts basal autophagy in cardiomyocytes by decreasing lysosome contentes_ES
Document typedc.typeArtículo de revistaes_ES
Catalogueruchile.catalogadortjnes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES


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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile