Increased amyloid β-peptide uptake in skeletal muscle is induced by hyposialylation and may account for apoptosis in GNE myopathy
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- dc.contributor.author Bosch Morató, Mònica, 1986-ca
- dc.contributor.author Iriondo, Cintaca
- dc.contributor.author Guivernau Almazán, Biuse, 1988-ca
- dc.contributor.author Valls Comamala, Victòria, 1987-ca
- dc.contributor.author Vidal, Noemíca
- dc.contributor.author Olivé, Montseca
- dc.contributor.author Querfurth, Henryca
- dc.contributor.author Muñoz López, Francisco José, 1964-ca
- dc.date.accessioned 2016-06-10T14:50:15Z
- dc.date.available 2016-06-10T14:50:15Z
- dc.date.issued 2016
- dc.description.abstract GNE myopathy is an autosomal recessive muscular disorder of young adults characterized by progressive skeletal muscle weakness and wasting. It is caused by a mutation in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, which encodes a key enzyme in sialic acid biosynthesis. The mutated hypofunctional GNE is associated with intracellular accumulation of amyloid β-peptide (Aβ) in patient muscles through as yet unknown mechanisms. We found here for the first time that an experimental reduction in sialic acid favors Aβ1-42 endocytosis in C2C12 myotubes, which is dependent on clathrin and heparan sulfate proteoglycan. Accordingly, Aβ1-42 internalization in myoblasts from a GNE myopathy patient was enhanced. Next, we investigated signal changes triggered by Aβ1-42 that may underlie toxicity. We observed that p-Akt levels are reduced in step with an increase in apoptotic markers in GNE myopathy myoblasts compared to control myoblasts. The same results were experimentally obtained when Aβ1-42 was overexpressed in myotubes. Hence, we propose a novel disease mechanism whereby hyposialylation favors Aβ1-42 internalization and the subsequent apoptosis in myotubes and in skeletal muscle from GNE myopathy patients.ca
- dc.description.sponsorship This work was supported by Fundació la Marató de TV3 (100310); Supported by the Plan Estatal de I+D+I 2013-2016 and the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Grants PI13/00408, PI08/00574 and Red HERACLES RD12/0042/0014) and FEDER; Generalitat de Catalunya (SGR09-1369).
- dc.format.mimetype application/pdfca
- dc.identifier.citation Bosch-Morató M, Iriondo C, Guivernau B, Valls-Comamala V, Vidal N, Olivé M et al. Increased amyloid β-peptide uptake in skeletal muscle is induced by hyposialylation and may account for apoptosis in GNE myopathy. Oncotarget. 2016; 7(12): 13354-13371. DOI 10.18632/oncotarget.7997ca
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.7997
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/26905
- dc.language.iso engca
- dc.publisher Impact Journalsca
- dc.relation.ispartof Oncotarget. 2016; 7(12): 13354-13371
- dc.rights © The Authors. This is the published version of an article http://dx.doi.org/10.18632/oncotarget.7997 that appeared in the journal Oncotarget. It is published under a Creative Commons Attribution 3.0 Licenseca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/3.0/ca
- dc.subject.keyword Akt
- dc.subject.keyword Aβ
- dc.subject.keyword GNE myopathy
- dc.subject.keyword Gerotarget
- dc.subject.keyword Apoptosis
- dc.subject.keyword Endocytosis
- dc.subject.other Músculsca
- dc.title Increased amyloid β-peptide uptake in skeletal muscle is induced by hyposialylation and may account for apoptosis in GNE myopathyca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca