|
Título:
|
Sir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregation
|
|
Autor/a:
|
Sorolla Bardají, Maria Alba; Nierga, Clara; Rodríguez Colman, Maria José; Reverter Branchat, Gemma; Arenas, Alicia; Tamarit Sumalla, Jordi; Ros Salvador, Joaquim; Cabiscol Català, Elisa
|
|
Notas:
|
Huntington 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.
This 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. |
|
Materia(s):
|
-Huntington disease
-Yeast
-Sir2 |
|
Derechos:
|
(c) Elsevier, 2011
info:eu-repo/semantics/restrictedAccess |
|
Tipo de documento:
|
article
publishedVersion |
|
Editor:
|
Elsevier
|
|
Compartir:
|
|
