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Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease

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dc.contributor.author Tajes Orduña, Marta
dc.contributor.author Eraso Pichot, Abel
dc.contributor.author Rubio Moscardó, Fanny
dc.contributor.author Guivernau Almazán, Biuse, 1988-
dc.contributor.author Bosch Morató, Mònica, 1986-
dc.contributor.author Valls Comamala, Victòria, 1987-
dc.contributor.author Miscione, Gian Pietro
dc.contributor.author Villà i Freixa, Jordi
dc.contributor.author Suzuki, Toshiharu
dc.contributor.author Muñoz López, Francisco José, 1964-
dc.date.accessioned 2016-06-09T17:15:06Z
dc.date.available 2016-06-09T17:15:06Z
dc.date.issued 2014
dc.identifier.citation Tajes M, Eraso-Pichot A, Rubio-Moscardó F, Guivernau B, Bosch-Morató M, Valls-Comamala V et al. Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease. Neuroscience Letters. 2014; 580: 78-82. DOI 10.1016/j.neulet.2014.07.047
dc.identifier.issn 0304-3940
dc.identifier.uri http://hdl.handle.net/10230/26885
dc.description.abstract Alzheimer's disease (AD) is characterized by the oxidative stress generated from amyloid β-peptide (Aβ) aggregates. It produces protein nitrotyrosination, after the reaction with nitric oxide to form peroxynitrite, being triosephosphate isomerase (TPI) one of the most affected proteins. TPI is a glycolytic enzyme that catalyzes the interconversion between glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). Methylglyoxal (MG) is a by-product of TPI activity whose production is triggered when TPI is nitrotyrosinated. MG is harmful to cells because it glycates proteins. Here we found protein glycation when human neuroblastoma cells were treated with Aβ. Moreover glycation was also observed when neuroblastoma cells overexpressed mutated TPI where Tyr165 or Tyr209, the two tyrosines close to the catalytic center, were changed by Phe in order to mimic the effect of nitrotyrosination. The pathological relevance of these findings was studied by challenging cells with Aβ oligomers and MG. A significant decrease in mitochondrial transmembrane potential, one of the first apoptotic events, was obtained. Therefore, increasing concentrations of MG were assayed searching for MG effect in neuronal apoptosis. We found a decrease of the protective Bcl2 and an increase of the proapoptotic caspase-3 and Bax levels. Our results suggest that MG is triggering apoptosis in neurons and it would play a key role in AD neurodegeneration.
dc.description.sponsorship This work was 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, and Red HERACLES RD12/0042/0014) and FEDER Funds; the virtual physiological human (VPH) NoE (FP7-ICT-2007-2-223920), the Spanish Ministry of Science and Innovation (CTQ2008-00755; BFU2006-28430-E/BMC and RETIC COMBIOMED RD07/0067/0001); Generalitat de Catalunya (AGAUR BE-2 10240); and La Marató de TV3 (Nº 100310).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Neuroscience Letters. 2014; 580: 78-82
dc.rights © Elsevier http://dx.doi.org/10.1016/j.neulet.2014.07.047
dc.subject.other Alzheimer, Malaltia d'
dc.title Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.neulet.2014.07.047
dc.subject.keyword 3-Nitrotyrosine
dc.subject.keyword Alzheimer disease
dc.subject.keyword Amyloid
dc.subject.keyword Apoptosis
dc.subject.keyword Methylglyoxal
dc.subject.keyword Triose-phosphate isomerase
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223920
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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