2026-06-14T03:32:58Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/54002024-09-27T09:10:12Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Cardona, Maria
author
Lopez, Juan Antonio
author
Serafin, Anna
author
Rongvaux, Anthony
author
Inserte, Javier
author
Garcia-Dorado, David
author
Flavell, Richard
author
Llovera, Marta
author
Canas, Xavier
author
Vazquez, Jesus
author
Sanchis, Daniel
funder
Ministerio de Economía y Competitividad (España)
funder
Redes Temáticas de Investigación Cooperativa en Salud (RETICS) (España)
funder
Centro de Investigación Biomédica en Red - CIBERCV (Enfermedades Cardiovasculares)
funder
Instituto de Salud Carlos III
funder
Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)
2017-11-27T13:49:51Z
2017-11-27T13:49:51Z
2015
PLoS One. 2015; 10(6):e0131411
10.1371/journal.pone.0131411
1932-6203
PLoS One
26121671
http://hdl.handle.net/20.500.12105/5400
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.
eng
CELL-DEATH
DIFFERENTIATED CARDIOMYOCYTES
ENDONUCLEASE-G
APOPTOSIS
EXPRESSION
MICE
PROLIFERATION
PROTEINS
DNA
HYPERTROPHY
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the
Developing Mouse Heart
journal article
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