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ID 30787
本文ファイル
著者
Seki, Takahiro
Abe-Seki, Nana
Kikawada, Takahiro
Takahashi, Hideyuki
Adachi, Naoko
Saito, Naoaki
NDC
医学
抄録(英)
Several missense mutations in the protein kinase C gamma (gamma PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant gamma PKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant gamma PKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant gamma PKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant gamma PKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant gamma PKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant gamma PKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant gamma PKC.
掲載誌名
The Journal of Biological Chemistry
285巻
43号
開始ページ
33252
終了ページ
33264
出版年月日
2010-08-12
出版者
American Society for Biochemistry and Molecular Biology Inc
ISSN
0021-9258
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
関連情報URL
部局名
医歯薬学総合研究科