Oxidative stimuli affect polyglutamine aggregation and cell death in human mutant ataxin-1-expressing cells

Sung Jo Kim, Tae Soo Kim, Sunghoi Hong, Hyangshuk Rhim, Ick Young Kim, Seongman Kang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Spinocerebellar ataxia 1 (SCA1), one of the inherited polyglutamine neurodegenerative diseases, is associated with intracellular aggregates. However, the process of aggregate formation and the factors that influence aggregation remain unclear. Here, we show that oxidative stimuli and alteration of the cellular redox state significantly affect aggregation and cell death in cells expressing mutant ataxin-1, the SCA gene product. Treatment of cells with buthionine sulfoximine, hydrogen peroxide or t-butylhydroperoxide increased the formation of mutant ataxin-1 aggregates, but treatment with the anti-oxidant, N-acetylcysteine (NAC), decreased aggregate formation. Oxidative damage of mutant ataxin-1 protein increased its recruitment in nuclear aggregates and increased cell death. However, NAC treatments reduced cell death and the number of cells with abnormal morphology. Our results might give insight into the mechanism whereby polyglutamine proteins aggregate and suggest that treatment of appropriate antioxidant reagents might prevent progression of SCA1 and other polyglutamine diseases.

Original languageEnglish
Pages (from-to)21-24
Number of pages4
JournalNeuroscience Letters
Volume348
Issue number1
DOIs
Publication statusPublished - 2003 Sep 4

Keywords

  • Aggregate
  • Ataxin-1
  • Polyglutamine
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)

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