Show simple item record

dc.contributor.authorEtxebarria, Aitor
dc.contributor.authorBenito Vicente, Asier
dc.contributor.authorStef, M.
dc.contributor.authorOstolaza Echabe, Elena Amaya
dc.contributor.authorPalacios, Lourdes
dc.contributor.authorMartín Plágaro, César Augusto
dc.date.accessioned2024-02-08T11:22:28Z
dc.date.available2024-02-08T11:22:28Z
dc.date.issued2015-02
dc.identifier.citationAtherosclerosis 238(2) : 304-312 (2015)
dc.identifier.issn1879-1484
dc.identifier.issn0021-9150
dc.identifier.urihttp://hdl.handle.net/10810/65557
dc.description.abstractBackground: The LDL receptor (LDLR) is a Class I transmembrane protein critical for the clearance of cholesterol-containing lipoprotein particles. The N-terminal domain of the LDLR harbours the ligand-binding domain consisting of seven cysteine-rich repeats of approximately 40 amino acids each. Mutations in the LDLR binding domain may result in loss of receptor activity leading to familial hypercholesterolemia (FH). In this study the activity of six mutations located in the cysteine-rich repeats of the LDLR has been investigated. Methods: CHO-ldlA7 transfected cells with six different LDLR mutations have been used to analyse in vitro LDLR expression, lipoprotein binding and uptake. Immunoblotting of cell extracts, flow cytometry and confocal microscopy have been performed to determine the effects of these mutations. In silico analysis was also performed to predict the mutation effect. Results and conclusion: From the six mutations, p.Arg257Trp turned out to be a non-pathogenic LDLR variant whereas p.Cys116Arg, p.Asp168Asn, p.Asp172Asn, p.Arg300Gly and p.Asp301Gly were classified as binding-defective LDLR variants whose effect is not as severe as null allele mutations.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy and Competitiveness, Programa INNPACTO (grant N° IPT-2011-0817-010000) and from the Spanish Ministerio de Ciencia y Tecnología (Project BFU 2012–36241), and the Basque Government (Grupos Consolidados IT849-13 and ETORTEK Program).
dc.language.isoenges_ES
dc.publisherElsevier
dc.relationinfo:eu-repo/grantAgreement/MINECO/IPT-2011-0817-010000
dc.relationinfo:eu-repo/grantAgreement/MICIN/BFU 2012–36241
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectLDLRes_ES
dc.subjectmutations
dc.subjectfamilial hypercholesterolemia
dc.subjectligand binding domain
dc.subjectmutation class defect
dc.titleActivity-associated effect of LDL receptor missense variants located in the cysteine-rich repeatses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder© 2014 Elsevier under CC BY-NC-ND license*
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0021915014016487
dc.identifier.doi10.1016/j.atherosclerosis.2014.12.026.
dc.departamentoesBioquímica y biología moleculares_ES
dc.departamentoeuBiokimika eta biologia molekularraes_ES


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

© 2014 Elsevier under CC BY-NC-ND license
Except where otherwise noted, this item's license is described as © 2014 Elsevier under CC BY-NC-ND license