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dc.contributor.authorCardona, Maria
dc.contributor.authorLópez, Juan Antonio
dc.contributor.authorSerafín, Anna
dc.contributor.authorRongvaux, Anthony
dc.contributor.authorInserte Igual, Javier
dc.contributor.authorGarcía-Dorado, David
dc.contributor.authorFlavell, Richard
dc.contributor.authorLlovera i Tomàs, Marta
dc.contributor.authorCañas, Xavier
dc.contributor.authorVázquez, Jesús
dc.contributor.authorSanchis, Daniel
dc.description.abstractExecutioner caspase-3 and -7 are proteases promoting cell death but non-apoptotic roles are being discovered. The heart expresses caspases only during development, suggesting they contribute to the organ maturation process. Therefore, we aimed at identifying novel functions of caspases in heart development. We induced simultaneous deletion of executioner caspase-3 and -7 in the mouse myocardium and studied its effects. Caspase knockout hearts are hypoplastic at birth, reaching normal weight progressively through myocyte hypertrophy. To identify the molecular pathways involved in these effects, we used microarray-based transcriptomics and multiplexed quantitative proteomics to compare wild type and executioner caspase-deficient myocardium at different developmental stages. Transcriptomics showed reduced expression of genes promoting DNA replication and cell cycle progression in the neonatal caspase-deficient heart suggesting reduced myocyte proliferation, and expression of non-cardiac isoforms of structural proteins in the adult null myocardium. Proteomics showed reduced abundance of proteins involved in oxidative phosphorylation accompanied by increased abundance of glycolytic enzymes underscoring retarded metabolic maturation of the caspase-null myocardium. Correlation between mRNA expression and protein abundance of relevant genes was confirmed, but transcriptomics and proteomics indentified complementary molecular pathways influenced by caspases in the developing heart. Forced expression of wild type or proteolytically inactive caspases in cultured cardiomyocytes induced expression of genes promoting cell division. The results reveal that executioner caspases can modulate heart’s cellularity and maturation during development, contributing novel information about caspase biology and heart development.ca_ES
dc.description.sponsorshipThis work was partially supported by Ministerio de Economía y Competitividad (MINECO) (Grants SAF2010_19125 and SAF2013_44942 to D.S. and SAF2010-37926 and ProteoRed-PT13/0001/0017 to J.V.); Program Redes Temáticas de Investigación Cooperativa en Salud (RETICS) Grants RD12/0042/0035, RD12/0042/0056 and RD12/0042/0021, Red de Investigación Cardiovascular, RIC to DS, JV and DGD. and FIS-PI121738 to DGD. from Instituto de Salud Carlos III (ISCIII); Grant 2009SGR-346 from the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) to XC and DS. RAF is an investigator of the Howard Hughes Medical Institute.
dc.publisherPublic Library of Scienceca_ES
dc.relation.isformatofReproducció del document publicat a journal.pone.0131411ca_ES
dc.relation.ispartofPlos One, 2015, vol. 10, num. 6, p. 0131411ca_ES
dc.rightscc-by, (c) Cardona et al., 2015ca_ES
dc.subjectGene expressionca_ES
dc.subjectMuscle cellsca_ES
dc.subjectCell divisionca_ES
dc.subject.otherExpressió gènicaca_ES
dc.subject.otherCicle cel·lularca_ES
dc.subject.otherCèl·lules muscularsca_ES
dc.subject.otherDivisió cel·lularca_ES
dc.titleExecutioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heartca_ES
dc.identifier.doi journal.pone.0131411

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