Polyglutamine-expanded ataxin-1 recruits Cu/Zn-superoxide dismutase into the nucleus of HeLa cells.
Spinocerebellar ataxia 1 (SCA1) is an inherited neurodegenerative disorder caused by expansion of the polyglutamine stretch in ataxin-1, the SCA1 gene product. Polyglutamine expansion leads to the aggregation of ataxin-1 proteins. Superoxide dismutases (SODs) are involved in the pathogenesis of other aggregate-forming neurodegenerative diseases and are known to localize in the cytoplasm. Here, we show that Cu/Zn-SOD is translocated into the nucleus of HeLa cells in the presence of expanded ataxin-1, whereas Mn-SOD is localized in the cytoplasm: the longer the expansion of polyglutamine, the higher the level of translocation of Cu/Zn-SOD. In addition, the oxidation of intracellular proteins occurs with higher frequency in the presence of mutant ataxin-1 (82Q), suggesting that the functional activity of Cu/Zn-SOD might be decreased by mutant ataxin-1. We demonstrate that mutant ataxin-1-expressing cells encounter mitochondrial dysfunction in the conditions of oxidative stress. Our results suggest that polyglutamine-expanded ataxin-1 increases the levels of reactive oxygen species in HeLa cells.
Kim
Sung-Jo
SJ
Laboratory of Molecular Genetics, Graduate School of Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Kim
Tae-Soo
TS
Kim
Ick Young
IY
Hong
Sunghoi
S
Rhim
Hyangshuk
H
Kang
Seongman
S
D021581:Active Transport, Cell Nucleus; D000067696:Ataxin-1; D000067528:Ataxins; D002467:Cell Nucleus / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D018384:Oxidative Stress; D010455:Peptides / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D017382:Reactive Oxygen Species; C097188:polyglutamine; D013482:Superoxide Dismutase