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

Tajes Orduña, Marta; Eraso Pichot, Abel; Rubio Moscardó, Fanny; Guivernau Almazán, Biuse, 1988-; Bosch Morató, Mònica, 1986-; Valls Comamala, Victòria, 1987-; Miscione, Gian Pietro; Villà i Freixa, Jordi; Suzuki, Toshiharu; Muñoz López, Francisco José, 1964-

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, Martaca
dc.contributor.author Eraso Pichot, Abelca
dc.contributor.author Rubio Moscardó, Fannyca
dc.contributor.author Guivernau Almazán, Biuse, 1988-ca
dc.contributor.author Bosch Morató, Mònica, 1986-ca
dc.contributor.author Valls Comamala, Victòria, 1987-ca
dc.contributor.author Miscione, Gian Pietroca
dc.contributor.author Villà i Freixa, Jordica
dc.contributor.author Suzuki, Toshiharuca
dc.contributor.author Muñoz López, Francisco José, 1964-ca
dc.date.accessioned 2016-06-09T17:15:06Z
dc.date.available 2016-06-09T17:15:06Z
dc.date.issued 2014
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.ca
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/pdfca
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.2014.07.047ca
dc.identifier.doi http://dx.doi.org/10.1016/j.neulet.2014.07.047
dc.identifier.issn 0304-3940
dc.identifier.uri http://hdl.handle.net/10230/26885
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof Neuroscience Letters. 2014;580:78-82
dc.relation.ispartof info:eu-repo/grantAgreement/ES/2PN/BFU2006-28430-E
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223920
dc.rights.accessRights info:eu-repo/semantics/openAccessca
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.subject.other Alzheimer, Malaltia d'ca
dc.title Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's diseaseca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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