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Authordc.contributor.authorSánchez Vergara, Gina 
Authordc.contributor.authorChalmers, Stefanie 
Authordc.contributor.authorAhumada, Xavier 
Authordc.contributor.authorMontecinos, Luis 
Authordc.contributor.authorOlmedo Alegría, Ivonne Odette 
Authordc.contributor.authorEisner, Verónica 
Authordc.contributor.authorRiveros, Ana 
Authordc.contributor.authorKogan, Marcelo J. 
Authordc.contributor.authorLavandero González, Sergio
Authordc.contributor.authorPedrozo Cibils, Zully 
Authordc.contributor.authorDonoso Laurent, Paulina 
Admission datedc.date.accessioned2020-06-30T23:24:54Z
Available datedc.date.available2020-06-30T23:24:54Z
Publication datedc.date.issued2020
Cita de ítemdc.identifier.citationPLoS ONE 15(5): e0233591. 2020es_ES
Identifierdc.identifier.other10.1371/journal.pone.0233591
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/175714
Abstractdc.description.abstractThe heart is critically dependent on mitochondrial respiration for energy supply. Ischemia decreases oxygen availability, with catastrophic consequences for cellular energy systems. After a few minutes of ischemia, the mitochondrial respiratory chain halts, ATP levels drop and ion gradients across cell membranes collapse. Activation of cellular proteases and generation of reactive oxygen species by mitochondria during ischemia alter mitochondrial membrane permeability, causing mitochondrial swelling and fragmentation and eventually cell death. The mitochondria, therefore, are important targets of cardioprotection against ischemic injury. We have previously shown that ixazomib (IXA), a proteasome inhibitor used for treating multiple myeloma, effectively reduced the size of the infarct produced by global ischemia in isolated rat hearts and prevented degradation of the sarcoplasmic reticulum calcium release channel RyR2. The aim of this work was to further characterize the protective effect of IXA by determining its effect on mitochondrial morphology and function after ischemia. We also quantified the effect of IXA on levels of mitofusin-2, a protein involved in maintaining mitochondrial morphology and mitochondria-SR communication. We found that mitochondria were significantly preserved and functional parameters such as oxygen consumption, the ability to generate a membrane potential, and glutathione content were improved in mitochondria isolated from hearts perfused with IXA prior to ischemia. IXA also blocked the release of cytochrome c observed in ischemia and significantly preserved mitofusin-2 integrity. These beneficial effects resulted in a significant decrease in the left ventricular end diastolic pressure upon reperfusion and a smaller infarct in isolated hearts.es_ES
Patrocinadordc.description.sponsorshipComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 1110257 1130407 11170962 1180613es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherPublic Library Sciencees_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.sourcePLoS ONEes_ES
Keywordsdc.subjectMitofusin 2es_ES
Keywordsdc.subjectReperfusion injuryes_ES
Keywordsdc.subjectCardiac-functiones_ES
Keywordsdc.subjectMicrodomainses_ES
Keywordsdc.subjectGlutathionees_ES
Keywordsdc.subjectExpressiones_ES
Keywordsdc.subjectReticulumes_ES
Keywordsdc.subjectProteinses_ES
Títulodc.titleInhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemiaes_ES
Document typedc.typeArtículo de revistaes_ES
dcterms.accessRightsdcterms.accessRightsAcceso Abierto
Catalogueruchile.catalogadorlajes_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