dc.contributor.author | Cardona, Maria | |
dc.contributor.author | Lopez, Juan Antonio | |
dc.contributor.author | Serafin, Anna | |
dc.contributor.author | Rongvaux, Anthony | |
dc.contributor.author | Inserte, Javier | |
dc.contributor.author | Garcia-Dorado, David | |
dc.contributor.author | Flavell, Richard | |
dc.contributor.author | Llovera, Marta | |
dc.contributor.author | Canas, Xavier | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Sanchis, Daniel | |
dc.date.accessioned | 2017-11-27T13:49:51Z | |
dc.date.available | 2017-11-27T13:49:51Z | |
dc.date.issued | 2015 | |
dc.identifier | ISI:000358150400106 | |
dc.identifier.citation | PLoS One. 2015; 10(6):e0131411 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5400 | |
dc.description.abstract | Executioner 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. | |
dc.description.sponsorship | This work was partially supported by Ministerio de Economia 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 Tematicas de Investigacion Cooperativa en Salud (RETICS) Grants
RD12/0042/0035, RD12/0042/0056 and RD12/0042/0021, Red de Investigacion
Cardiovascular, RIC to DS, JV and DGD. and FIS-PI121738 to DGD. from
Instituto de Salud Carlos III (ISCIII); Grant 2009SGR-346 from the
Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) to XC and
DS. RAF is an investigator of the Howard Hughes Medical Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. | |
dc.language.iso | eng | |
dc.publisher | Public Library of Science (PLOS) | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | CELL-DEATH | |
dc.subject | DIFFERENTIATED CARDIOMYOCYTES | |
dc.subject | ENDONUCLEASE-G | |
dc.subject | APOPTOSIS | |
dc.subject | EXPRESSION | |
dc.subject | MICE | |
dc.subject | PROLIFERATION | |
dc.subject | PROTEINS | |
dc.subject | DNA | |
dc.subject | HYPERTROPHY | |
dc.title | Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the
Developing Mouse Heart | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 26121671 | |
dc.format.volume | 10 | |
dc.identifier.doi | 10.1371/journal.pone.0131411 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España) | |
dc.contributor.funder | Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pone.0131411 | |
dc.identifier.journal | PLoS One | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | MINECO/ICTI2013-2016/SAF2013_44942 | es_ES |
dc.rights.accessRights | open access | es_ES |