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dc.contributor.author
Obis, Elia
dc.contributor.author
Irazusta, Verónica Patricia
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dc.contributor.author
Sanchis, Daniel
dc.contributor.author
Ros, Joaquim
dc.contributor.author
Tamarit, Jordi
dc.date.available
2016-03-11T19:51:38Z
dc.date.issued
2014-08
dc.identifier.citation
Obis, Elia; Irazusta, Verónica Patricia; Sanchis, Daniel; Ros, Joaquim; Tamarit, Jordi; Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism; Elsevier; Free Radical Biology and Medicine; 73; 8-2014; 21-33
dc.identifier.issn
0891-5849
dc.identifier.uri
http://hdl.handle.net/11336/4751
dc.description.abstract
Friedreich ataxia (FRDA) is a hereditary disease caused by deficient frataxin expression. This mitochondrial protein has been related to iron homeostasis, energy metabolism, and oxidative stress. Patients with FRDA experience neurologic alterations and cardiomyopathy, which is the leading cause of death. The specific effects of Frataxin depletion on cardiomyocytes are poorly understood because no appropriate cardiac cellular model is available to researchers. To address this research need, we present a model based on primary cultures of neonatal rat ventricular myocytes (NRVM) and shRNA interference. Using this approach, frataxin was reduced down to 5% to 30% of control protein levels after 7 days of transduction. At this stage the activity and amount of the iron-sulfur protein aconitase, in vitro activities of several OXPHOS components, levels of iron-regulated mRNAs or the ATP/ADP ratio were comparable to controls. However, NRVM exhibited markers of oxidative stress and a disorganized mitochondrial network with enlarged mitochondria. Lipids, the main energy source of heart cells, also underwent a clear metabolic change, indicated by the increased presence of lipid droplets and induction of medium-chain acyl-CoA dehydrogenase. These results indicate that mitochondria and lipid metabolism are primary targets of frataxin deficiency in NRVM. Therefore, they contribute to the understanding of cardiac-specific mechanisms occurring in FRDA and give clues for the design of cardiac specific treatment strategies for FRDA.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Friedreich Ataxia,
dc.subject
Mitochondria
dc.subject
Iron
dc.subject
Lipid Metabolism
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Frataxin deficiency in neonatal rat ventricular myocytes targets mitochondria and lipid metabolism
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
73
dc.journal.pagination
21-33
dc.journal.pais
Países Bajos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Obis, Elia. Universitat de Leida. Departament de Ciències Mèdiques Bàsiques; España
dc.description.fil
Fil: Irazusta, Verónica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Investigación para la Industria Química (i); Argentina
dc.description.fil
Fil: Sanchis, Daniel. Universitat de Leida. Departament de Ciències Mèdiques Bàsiques; España
dc.description.fil
Fil: Ros, Joaquim. Universitat de Leida. Departament de Ciències Mèdiques Bàsiques; España
dc.description.fil
Fil: Tamarit, Jordi. Universitat de Leida. Departament de Ciències Mèdiques Bàsiques; España
dc.journal.title
Free Radical Biology and Medicine
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0891584914001853
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.freeradbiomed.2014.04.016
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/issn/0891-5849
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