Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells
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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
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NDC |
医学
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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.
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掲載誌名 |
The Journal of Biological Chemistry
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巻 | 285巻
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号 | 43号
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開始ページ | 33252
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終了ページ | 33264
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出版年月日 | 2010-08-12
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出版者 | American Society for Biochemistry and Molecular Biology Inc
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ISSN | 0021-9258
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NCID | |
出版者DOI | |
言語 |
英語
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NII資源タイプ |
学術雑誌論文
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広大資料タイプ |
学術雑誌論文
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DCMIタイプ | text
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フォーマット | application/pdf
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著者版フラグ | author
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権利情報 | Copyright (c) 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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関連情報URL | |
部局名 |
医歯薬学総合研究科
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