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, Martaca
  • dc.contributor.author Eraso Pichot, Abelca
  • dc.contributor.author Rubio Moscardó, Fannyca
  • dc.contributor.author Guivernau Almazán, Biuse, 1988-ca
  • dc.contributor.author Ramos Fernández, Eva, 1984-ca
  • dc.contributor.author Bosch Morató, Mònica, 1986-ca
  • dc.contributor.author Guix Ràfols, Francesc Xavierca
  • dc.contributor.author Clarimón Echevarría, Jordica
  • dc.contributor.author Miscione, Gian Pietroca
  • dc.contributor.author Boada, Mercèca
  • dc.contributor.author Gil Gómez, Gabrielca
  • dc.contributor.author Suzuki, Toshiharuca
  • dc.contributor.author Molina, Henrikca
  • dc.contributor.author Villà i Freixa, Jordica
  • dc.contributor.author Vicente García, Rubén, 1978-ca
  • dc.contributor.author Muñoz López, Francisco José, 1964-ca
  • dc.date.accessioned 2016-06-09T17:47:51Z
  • dc.date.available 2016-06-09T17:47:51Z
  • dc.date.issued 2014
  • 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.ca
  • 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/pdfca
  • 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-131685ca
  • dc.identifier.doi http://dx.doi.org/10.3233/JAD-131685
  • dc.identifier.issn 1387-2877
  • dc.identifier.uri http://hdl.handle.net/10230/26887
  • dc.language.iso engca
  • dc.publisher IOS Pressca
  • dc.relation.ispartof Journal of Alzheimer's disease. 2014;41(1):273-88
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-16725
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223920
  • dc.rights The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-131685ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • 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.subject.other Alzheimer, Malaltia d'ca
  • dc.title Methylglyoxal produced by amyloid-β peptide-induced nitrotyrosination of triosephosphate isomerase triggers neuronal death in Alzheimer's diseaseca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/acceptedVersionca

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