Apoptotic cell death and altered calcium homeostasis caused by frataxin depletion in dorsal root ganglia neurons can be prevented by BH4 domain of Bcl-xL protein

Simple item page
dc.contributor.authorTasheva, Stefka Mincheva
dc.contributor.authorObis Monné, Èlia
dc.contributor.authorTamarit Sumalla, Jordi
dc.contributor.authorRos Salvador, Joaquim
dc.date.accessioned2016-05-31T11:31:52Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2014
dc.description.abstractFriedreich ataxia (FRDA) is a neurodegenerative disease characterized by a decreased expression of the mitochondrial protein frataxin. Major neurological symptoms of the disease are due to degeneration of dorsal root ganglion (DRG) sensory neurons. In this studywe have explored the neurodegenerative events occurring by frataxin depletion on primary cultures of neurons obtained from rat DRGs. Reduction of 80% of frataxin levels in these cellswasachievedbytransduction with lentivirus containingshRNAsilencing sequences. Frataxin depletion caused mitochondrial membrane potential decrease, neurite degeneration and apoptotic cell death. A marked increase of free intracellular Ca21 levels and alteration in Ca21-mediated signaling pathways was also observed, thus suggesting that altered calcium homeostasis can play a pivotal role in neurodegeneration caused by frataxin deficiency. These deleterious effects were reverted by the addition of a cell-penetrant TAT peptidecoupled to theBH4,the anti-apoptoticdomainof Bcl-xL. Treatmentof cultured frataxin-depletedneurons with TAT-BH4 was able to restore the free intracellular Ca21 levels and protect the neurons from degeneration. These observations open the possibility of new therapies of FRDA based on modulating the Ca21 signaling and prevent apoptotic process to protect DRG neurons from neurodegeneration.ca_ES
dc.description.sponsorshipThiswork was supported by grants from Ministerio de Economia y Competitividad, Spain (BFU2010-19193 and CSD2007-00020 Consolider Ingenio 2010) and Generalitat de Catalunya (SGR2009-00196) to J.R. and La Marató de TV3 2010 to J.T.).ca_ES
dc.identifier.doihttps://doi.org/10.1093/hmg/ddt576
dc.identifier.idgrec021515
dc.identifier.issn0964-6906
dc.identifier.urihttp://hdl.handle.net/10459.1/57124
dc.language.isoengca_ES
dc.publisherOxford University Pressca_ES
dc.relationinfo:eu-repo/grantAgreement/MICINN//BFU2010-19193/ES/ANALISIS PROTEOMICO Y FUNCIONAL DE LOS EFECTOS DEL ESTRES OXIDATIVO Y LA DESREGULACION DE LA HOMEOSTASIS DEL HIERRO EN MODELOS CELULARES DE ATAXIA DE FRIEDREICH/ca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1093/hmg/ddt576ca_ES
dc.relation.ispartofHuman Molecular Genetics, 2014, vol. 23, núm. 7, p. 1829-1841ca_ES
dc.rights(c) Oxford University Press, 2014ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.titleApoptotic cell death and altered calcium homeostasis caused by frataxin depletion in dorsal root ganglia neurons can be prevented by BH4 domain of Bcl-xL proteinca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
Files
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Articles publicats (Ciències Mèdiques Bàsiques)
Articles publicats (Grup de Recerca en Estrès Cel·lular i Supervivència en Models Eucariotes)
Articles publicats (IRBLleida)
Publicacions de projectes de recerca del Plan Nacional