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dc.contributor.authorSorolla Bardají, Maria Alba
dc.contributor.authorRodríguez Colman, Maria José
dc.contributor.authorTamarit Sumalla, Jordi
dc.contributor.authorOrtega, Zaira
dc.contributor.authorLucas, José J.
dc.contributor.authorFerrer, Isidre
dc.contributor.authorRos Salvador, Joaquim
dc.contributor.authorCabiscol Català, Elisa
dc.date.accessioned2016-06-07T09:59:00Z
dc.date.issued2010
dc.identifier.issn0891-5849
dc.identifier.urihttp://hdl.handle.net/10459.1/57169
dc.description.abstractHuntington disease (HD) is an inherited neurodegenerative disorder that initially affects the striatum and progressively the cortex. Oxidative stress in HD has been described as important to disease progression. In this study, protein carbonylation, used as a marker of protein oxidation, was analyzed in human brain striatum. A comparison of HD samples tomatched controls identified 13 carbonylated proteins, including enzymes involved in the glycolytic pathway and mitochondrial proteins related to ATP production. Oxidation of the mitochondrial enzymes resulted in decreased catalytic activity, in good agreement with the energy deficiency observed in HD. Wealso found carbonylation of pyridoxal kinase and antiquitin 1, both involved in themetabolismof pyridoxal 5- phosphate, the active formof vitamin B6. The Tet/HD94 conditionalmousemodel allowed us to demonstrate that increased carbonylation in striatum is dependent on mutant huntingtin expression. As in humans, pyridoxal kinase showed decreased levels and was highly carbonylated in the gene-on mice; these modifications were reverted in the gene-offmice. Wehypothesize that both pyridoxal kinase and antiquitin 1 oxidation could result in decreased pyridoxal 5-phosphate availability necessary as a cofactor in transaminations, synthesis of glutathione, and synthesis of GABA and dopamine, two neurotransmitters that play a key role in HD pathology.ca_ES
dc.description.sponsorshipThis work was supported by Grants BFU2007-66249 and CSD2007- 20 Consolider Ingenio 2010 from the Ministerio de Ciencia e Innovación (Spain) and SGR2009-00196 from the Generalitat de Catalunya. M.A. Sorolla and M.J. Rodriguez-Colman are recipients of Ph.D. fellowships from the Ministerio de Ciencia e Innovación. Work by the J.J. Lucas team was supported by the Ministerio de Ciencia e Innovación, CiberNed, Comunidad Autónoma de Madrid, and Fundación Ramón Areces.ca_ES
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationinfo:eu-repo/grantAgreement/MEC//BFU2007-66249/ES/ESTRES OXIDATIVO, ENVEJECIMIENTO CELULAR, HOMEOSTASIS DEL HIERRO Y PATOLOGIAS RELACIONADAS EN S. CEREVISIAE COMO MODELO CELULAR/
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.freeradbiomed.2010.05.016ca_ES
dc.relation.ispartofFree Radical Biology and Medicine, 2010, vol. 49, núm. 4, p. 612-621ca_ES
dc.rights(c) Elsevier, 2010ca_ES
dc.subjectHuntington diseaseca_ES
dc.subjectOxyproteomeca_ES
dc.subjectOxidative stressca_ES
dc.titleProtein oxidation in Huntington disease affects energy production and vitamin B6 metabolismca_ES
dc.typearticleca_ES
dc.identifier.idgrec015962
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2010.05.016
dc.date.embargoEndDate2025-01-01


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