Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease
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...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/26885 |
| Acceso en línea: | http://hdl.handle.net/10230/26885 http://dx.doi.org/10.1016/j.neulet.2014.07.047 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer, Malaltia d&apos 3-Nitrotyrosine Alzheimer disease Amyloid Apoptosis Methylglyoxal Triose-phosphate isomerase |
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Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's diseaseTajes Orduña, MartaEraso Pichot, AbelRubio Moscardó, FannyGuivernau Almazán, Biuse, 1988-Bosch Morató, Mònica, 1986-Valls Comamala, Victòria, 1987-Miscione, Gian PietroVillà i Freixa, JordiSuzuki, ToshiharuMuñoz López, Francisco José, 1964-Alzheimer, Malaltia d&apos3-NitrotyrosineAlzheimer diseaseAmyloidApoptosisMethylglyoxalTriose-phosphate isomeraseAlzheimer'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.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).Elsevier201620162014info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/26885http://dx.doi.org/10.1016/j.neulet.2014.07.047reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNeuroscience Letters. 2014;580:78-82info:eu-repo/grantAgreement/ES/2PN/BFU2006-28430-Einfo:eu-repo/grantAgreement/EC/FP7/223920© Elsevier http://dx.doi.org/10.1016/j.neulet.2014.07.047info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/268852026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| title |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| spellingShingle |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease Tajes Orduña, Marta Alzheimer, Malaltia d&apos 3-Nitrotyrosine Alzheimer disease Amyloid Apoptosis Methylglyoxal Triose-phosphate isomerase |
| title_short |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| title_full |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| title_fullStr |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| title_full_unstemmed |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| title_sort |
Methylglyoxal reduces mitochondrial potential and activates Bax and caspase-3 in neurons: implications for alzheimer's disease |
| dc.creator.none.fl_str_mv |
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- |
| author |
Tajes Orduña, Marta |
| author_facet |
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- |
| author_role |
author |
| author2 |
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- |
| author2_role |
author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Alzheimer, Malaltia d&apos 3-Nitrotyrosine Alzheimer disease Amyloid Apoptosis Methylglyoxal Triose-phosphate isomerase |
| topic |
Alzheimer, Malaltia d&apos 3-Nitrotyrosine Alzheimer disease Amyloid Apoptosis Methylglyoxal Triose-phosphate isomerase |
| description |
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. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2016 2016 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/26885 http://dx.doi.org/10.1016/j.neulet.2014.07.047 |
| url |
http://hdl.handle.net/10230/26885 http://dx.doi.org/10.1016/j.neulet.2014.07.047 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Neuroscience Letters. 2014;580:78-82 info:eu-repo/grantAgreement/ES/2PN/BFU2006-28430-E info:eu-repo/grantAgreement/EC/FP7/223920 |
| dc.rights.none.fl_str_mv |
© Elsevier http://dx.doi.org/10.1016/j.neulet.2014.07.047 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
© Elsevier http://dx.doi.org/10.1016/j.neulet.2014.07.047 |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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