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ID 30787
file
creator
Seki, Takahiro
Abe-Seki, Nana
Kikawada, Takahiro
Takahashi, Hideyuki
Adachi, Naoko
Saito, Naoaki
NDC
Medical sciences
abstract
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.
journal title
The Journal of Biological Chemistry
volume
Volume 285
issue
Issue 43
start page
33252
end page
33264
date of issued
2010-08-12
publisher
American Society for Biochemistry and Molecular Biology Inc
issn
0021-9258
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
relation url
department
Graduate School of Biomedical Science