Show simple item record

dc.contributor.authorFafián Labora, Juan Antonio
dc.contributor.authorMorente López, Miriam
dc.contributor.authorDe-Toro, Javier
dc.contributor.authorArufe, M.C.
dc.date.accessioned2021-08-17T07:40:27Z
dc.date.available2021-08-17T07:40:27Z
dc.date.issued2021-07-07
dc.identifier.citationFafián-Labora JA, Morente-López M, de Toro FJ, Arufe MC. High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome. Int J Mol Sci. 2021 Jul 7;22(14):7327.es_ES
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/2183/28256
dc.description.abstract[Abstract] Hutchinson–Gilford progeria syndrome (HGPS) is a deadly childhood disorder, which is considered a very rare disease. It is caused by an autosomal dominant mutation on the LMNA gene, and it is characterized by accelerated aging. Human cell lines from HGPS patients and healthy parental controls were studied in parallel using next-generation sequencing (NGS) to unravel new non-previously altered molecular pathways. Nine hundred and eleven transcripts were differentially expressed when comparing healthy versus HGPS cell lines from a total of 21,872 transcripts; ITPR1, ITPR3, CACNA2D1, and CAMK2N1 stood out among them due to their links with calcium signaling, and these were validated by Western blot analysis. It was observed that the basal concentration of intracellular Ca2+ was statistically higher in HGPS cell lines compared to healthy ones. The relationship between genes involved in Ca2+ signaling and mitochondria-associated membranes (MAM) was demonstrated through cytosolic calcium handling by means of an automated fluorescent plate reading system (FlexStation 3, Molecular Devices), and apoptosis and mitochondrial ROS production were examined by means of flow cytometry analysis. Altogether, our data suggest that the Ca2+ signaling pathway is altered in HGPS at least in part due to the overproduction of reactive oxygen species (ROS). Our results unravel a new therapeutic window for the treatment of this rare disease and open new strategies to study pathologies involving both accelerated and healthy aging.es_ES
dc.description.sponsorshipThis work was funded by the Spanish National Health Institute Carlos III (PI20/00497) awarded to M.C.A. Furthermore, J.A.F.-L. is funded by the Xunta de Galicia Fellowship (ED481D-2021-020)es_ES
dc.description.sponsorshipXunta de Galicia; ED481D-2021-020
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relationinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PI20%2F00497/ES/TERAPIA CELULAR CON MICRO ARN Y VESICULAS EXTRACELULARES PARA EL TRATAMIENTO DE LA INFLAMACION CRONICA EN UN MODELO DE OA. (TERAPIA LIBRE DE CELULAS)/
dc.relation.urihttps://doi.org/10.3390/ijms22147327es_ES
dc.rightsCreative Commons Attribution 4.0 International License (CC-BY 4.0)es_ES
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectHGPSes_ES
dc.subjectCa2+ signalinges_ES
dc.subjectGRP75es_ES
dc.subjectGRP78es_ES
dc.subjectNACes_ES
dc.subjectROSes_ES
dc.titleHigh-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndromees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessinfo:eu-repo/semantics/openAccesses_ES
UDC.journalTitleInternational Journal of Molecular Scienceses_ES
UDC.volume22es_ES
UDC.issue14es_ES
UDC.startPage7327es_ES
dc.identifier.doi10.3390/ijms22147327


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record