Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart
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 deve...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487935/ |
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pubmed-44879352015-07-02 Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart Cardona, Maria López, Juan Antonio Serafín, Anna Rongvaux, Anthony Inserte, Javier García-Dorado, David Flavell, Richard Llovera, Marta Cañas, Xavier Vázquez, Jesús Sanchis, Daniel Research Article 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. Public Library of Science 2015-06-29 /pmc/articles/PMC4487935/ /pubmed/26121671 http://dx.doi.org/10.1371/journal.pone.0131411 Text en © 2015 Cardona et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Cardona, Maria López, Juan Antonio Serafín, Anna Rongvaux, Anthony Inserte, Javier García-Dorado, David Flavell, Richard Llovera, Marta Cañas, Xavier Vázquez, Jesús Sanchis, Daniel |
| spellingShingle |
Cardona, Maria López, Juan Antonio Serafín, Anna Rongvaux, Anthony Inserte, Javier García-Dorado, David Flavell, Richard Llovera, Marta Cañas, Xavier Vázquez, Jesús Sanchis, Daniel Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| author_facet |
Cardona, Maria López, Juan Antonio Serafín, Anna Rongvaux, Anthony Inserte, Javier García-Dorado, David Flavell, Richard Llovera, Marta Cañas, Xavier Vázquez, Jesús Sanchis, Daniel |
| author_sort |
Cardona, Maria |
| title |
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| title_short |
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| title_full |
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| title_fullStr |
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| title_full_unstemmed |
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart |
| title_sort |
executioner caspase-3 and 7 deficiency reduces myocyte number in the developing mouse heart |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487935/ |
| _version_ |
1613242428771270656 |