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Methylglyoxal produced by amyloid-ß peptide-induced nitrotyrosination of triosephosphate isomerase triggers neuronal death in Alzheimer's disease.
Tajes, Marta; Eraso-Pichot, Abel; Rubio-Moscardó, Fanny; Guivernau, Biuse; Ramos-Fernández, Eva; Bosch-Morató, Mònica; Guix, Francesc Xavier; Clarimón, Jordi; Miscione, Gian Pietro; Boada, Mercé; Gil-Gómez, Gabriel; Suzuki, Toshiharu; Molina, Henrik; Villà-Freixa, Jordi; Vicente, Rubén; Muñoz, Francisco J.
Afiliación
  • Tajes M; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Eraso-Pichot A; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Rubio-Moscardó F; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Guivernau B; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Ramos-Fernández E; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Bosch-Morató M; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Guix FX; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Clarimón J; Alzheimer Laboratory, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
  • Miscione GP; Computational Biochemistry and Biophysics Laboratory, Research Program on Biomedical Informatics, DCEXS, IMIM/UPF, Barcelona, Spain Dipartimento di Chimica "G. Ciamician", Universitá degli Studi di Bologna, Italy.
  • Boada M; Memory Clinic, Fundació ACE. Institut Català de Neurociències Aplicades, Barcelona, Spain Neurology Department, Hospital Universitari Vall d'Hebron-Institut de Recerca, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.
  • Gil-Gómez G; IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
  • Suzuki T; Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
  • Molina H; Proteomics Unit, DCEXS, UPF and Centre de Regulació Genómica (CRG), Barcelona, Spain.
  • Villà-Freixa J; Computational Biochemistry and Biophysics Laboratory, Research Program on Biomedical Informatics, DCEXS, IMIM/UPF, Barcelona, Spain Escola Politécnica Superior, Universitat de Vic, Spain.
  • Vicente R; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
  • Muñoz FJ; Laboratory of Molecular Physiology and Channelopathies, Departament de Ciències Experimentals i de la Salut (DCEXS), Universitat Pompeu Fabra (UPF), Barcelona, Spain.
J Alzheimers Dis ; 41(1): 273-88, 2014.
Article en En | MEDLINE | ID: mdl-24614897
Amyloid-ß peptide (Aß) 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 Aß42 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 Aß42 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 Aß 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 Aß oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Piruvaldehído / Triosa-Fosfato Isomerasa / Péptidos beta-Amiloides / Apoptosis / Enfermedad de Alzheimer / Neuronas Tipo de estudio: Prognostic_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Piruvaldehído / Triosa-Fosfato Isomerasa / Péptidos beta-Amiloides / Apoptosis / Enfermedad de Alzheimer / Neuronas Tipo de estudio: Prognostic_studies Límite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: España