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Methylglyoxal produced by amyloid-β peptide-induced nitrotyrosination of triosephosphate isomerase triggers neuronal death in 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 Ramos Fernández, Eva, 1984-
dc.contributor.author Bosch Morató, Mònica, 1986-
dc.contributor.author Guix Ràfols, Francesc Xavier
dc.contributor.author Clarimón Echevarría, Jordi
dc.contributor.author Miscione, Gian Pietro
dc.contributor.author Boada, Mercè
dc.contributor.author Gil Gómez, Gabriel
dc.contributor.author Suzuki, Toshiharu
dc.contributor.author Molina, Henrik
dc.contributor.author Villà i Freixa, Jordi
dc.contributor.author Vicente García, Rubén, 1978-
dc.contributor.author Muñoz López, Francisco José, 1964-
dc.date.accessioned 2016-06-09T17:47:51Z
dc.date.available 2016-06-09T17:47:51Z
dc.date.issued 2014
dc.identifier.citation Tajes M, Eraso-Pichot A, Rubio-Moscardó F, Guivernau B, Ramos-Fernández E, Bosch-Morató M et al. Methylglyoxal produced by amyloid-β peptide-induced nitrotyrosination of triosephosphate isomerase triggers neuronal death in Alzheimer's disease. Journal of Alzheimer's disease. 2014;41(1):273-88. DOI: 10.3233/JAD-131685
dc.identifier.issn 1387-2877
dc.identifier.uri http://hdl.handle.net/10230/26887
dc.description.abstract Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center.
dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation (SAF2010-16725; Fondo de Investigación Sanitaria PI10/00587 and PI10/01076; Red HERACLES RD12/0042/0014- FEDER Funds; CTQ2008-00755; BFU2006-28430-E/BMC and RETIC COMBIOMED RD07/0067/0001); the virtual physiological human (VPH) NoE (FP7-ICT-2007-2-223920); Generalitat de Catalunya (AGAUR BE-2 10240; SGR2009-1369); and La Marató de TV3 (Nº 100310 and 100610).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher IOS Press
dc.relation.ispartof Journal of Alzheimer's disease. 2014;41(1):273-88
dc.rights The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-131685
dc.subject.other Alzheimer, Malaltia d'
dc.title Methylglyoxal produced by amyloid-β peptide-induced nitrotyrosination of triosephosphate isomerase triggers neuronal death in Alzheimer's disease
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3233/JAD-131685
dc.subject.keyword 3-nitrotyrosine
dc.subject.keyword Alzheimer's 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/ES/3PN/SAF2010-16725
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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