Sir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregation

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dc.contributor.authorSorolla Bardají, Maria Alba
dc.contributor.authorNierga, Clara
dc.contributor.authorRodríguez Colman, Maria José
dc.contributor.authorReverter Branchat, Gemma
dc.contributor.authorArenas, Alicia
dc.contributor.authorTamarit Sumalla, Jordi
dc.contributor.authorRos Salvador, Joaquim
dc.contributor.authorCabiscol Català, Elisa
dc.date.accessioned2016-05-30T08:40:56Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2011
dc.description.abstractHuntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG trinucleotide repeats, leading to an elongated polyglutamine sequence (polyQ) in the huntingtin protein. Misfolding of mutant polyQ proteins with expanded tracts results in aggregation, causing cytotoxicity. Oxidative stress in HD has been documented in humans as important to disease progression. Using yeast cells as a model of HD, we report that when grown at high glucose concentration, cells expressing mutant polyQ do not show apparent oxidative stress. At higher cell densities, when glucose becomes limiting and cells are metabolically shifting from fermentation to respiration, protein oxidation and catalase activity increases in relation to the length of the polyQ tract. Oxidative stress, either endogenous as a result of mutant polyQ expression or exogenously generated, increases Sir2 levels. D sir2 cells expressing expanded polyQ lengths show signs of oxidative stress even at the early exponential phase. In a wild-type background, isonicotinamide, a Sir2 activator, decreases mutant polyQ aggregation and the stress generated by expanded polyQ. Taken together, these results describe mutant polyQ proteins as being more toxic in respiring cells, causing oxidative stress and an increase in Sir2 levels. Activation of Sir2 would play a protective role against this toxicity.ca_ES
dc.description.sponsorshipThis work has been supported by Grants BFU2007-66249, BFU2010-17387 and CSD2007-20 Consolider Ingenio 2010 from the Ministerio de Ciencia e Innovación (Spain) and SGR2009-00196 from the Generalitat de Catalunya.ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.abb.2011.04.002
dc.identifier.idgrec016490
dc.identifier.issn0003-9861
dc.identifier.urihttp://hdl.handle.net/10459.1/57117
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.relationinfo:eu-repo/grantAgreement/MICINN//BFU2010-17387/ES/PAPEL DEL FACTOR DE TRANCRIPCION HCM1 EN LA BIOGENESIS MITOCONDRIAL ENVEJECIMIENTO Y LA LIMITACION DE NUTRIENTES EN S CEREVISIAE/
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.abb.2011.04.002ca_ES
dc.relation.ispartofArchives of Biochemistry and Biophysics, 2011, vol. 510, núm. 1, p.27-34ca_ES
dc.rights(c) Elsevier, 2011ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.subjectHuntington diseaseca_ES
dc.subjectYeastca_ES
dc.subjectSir2ca_ES
dc.titleSir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregationca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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