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

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.
Authors	Sung-Jo Kim, Tae-soo Kim, Sunghoi Hong, Hyangshuk Rhim, Ick Young Kim, Seongman Kang
Journal	Neuroscience letters (Neurosci Lett) Vol. 348 Issue 1 Pg. 21-4 (Sep 04 2003) ISSN: 0304-3940 [Print] Ireland
PMID	12893416 (Publication Type: Comparative Study, Journal Article)
Chemical References	ATXN1 protein, human Ataxin-1 Ataxins Atxn1 protein, rat Free Radical Scavengers Luminescent Proteins Nerve Tissue Proteins Nuclear Proteins Oxidants Peptides Radiation-Protective Agents Green Fluorescent Proteins polyglutamine Buthionine Sulfoximine tert-Butylhydroperoxide Hydrogen Peroxide Acetylcysteine
Topics	Acetylcysteine (pharmacology) Animals Ataxin-1 Ataxins Buthionine Sulfoximine (pharmacology) Cell Aggregation (physiology) Cell Death (physiology) Fluorescent Antibody Technique (methods) Free Radical Scavengers (pharmacology) Green Fluorescent Proteins HeLa Cells Humans Hydrogen Peroxide (pharmacology) Immunoblotting (methods) Luminescent Proteins (metabolism) Mutation Nerve Tissue Proteins (biosynthesis, genetics, physiology) Nuclear Proteins (biosynthesis, genetics, physiology) Oxidants (pharmacology) Oxidative Stress (drug effects, physiology) Peptides (immunology, metabolism) Radiation-Protective Agents (pharmacology) Rats Time Factors Transfection tert-Butylhydroperoxide (pharmacology)

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