Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/227955
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia |
Autor: | Alonso-Barroso, Esmeralda; Pérez, Belén CSIC ORCID; Ruiz Desviat, Lourdes; Richard, Eva CSIC ORCID | Palabras clave: | Propionic acidemia Cardiac dysfunction iPSC iPSC-derived cardiomyocytes Disease model |
Fecha de publicación: | 25-ene-2021 | Editor: | Multidisciplinary Digital Publishing Institute | Citación: | International Journal of Molecular Sciences 22(3): 1161 (2021) | Resumen: | Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation. | Descripción: | © 2021 by the authors | Versión del editor: | https://doi.org/10.3390/ijms22031161 | URI: | http://hdl.handle.net/10261/227955 | DOI: | 10.3390/ijms22031161 | ISSN: | 1661-6596 | E-ISSN: | 1422-0067 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
Cardiomyocytes_Alonso_PV_Art2021.pdf | 2,71 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
4
checked on 18-abr-2024
SCOPUSTM
Citations
5
checked on 19-abr-2024
WEB OF SCIENCETM
Citations
6
checked on 28-feb-2024
Page view(s)
112
checked on 21-abr-2024
Download(s)
167
checked on 21-abr-2024