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ID 47058
本文ファイル
著者
Mimori, Seisuke
Okuma, Yasunobu
Kawada, Koichi
Hosoi, Toru 大学院医歯薬保健学研究科(薬) 広大研究者総覧
Ozawa, Koichiro 大学院医歯薬保健学研究科(薬) 広大研究者総覧
Nomura, Yasuyuki
Hamana, Hiroshi
キーワード
4-phenylbutyrate
3-phenylpropionate
endoplasmic reticulum stress
NDC
医学
抄録(英)
Endoplasmic reticulum (ER) stress responses play an important role in neurodegenerative diseases. Sodium 4-phenylbutyrate (4-PBA) is a terminal aromatic substituted fatty acid that has been used for the treatment of urea cycle disorders. 4-PBA possesses in vitro chemical chaperone activity and reduces the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), which is involved in autosomal recessive juvenile parkinsonism (AR-JP). In this study, we show that terminal aromatic substituted fatty acids, including 3-phenylpropionate (3-PPA), 4-PBA, 5-phenylvaleric acid, and 6-phenylhexanoic acid, prevented the aggregation of lactalbumin and bovine serum albumin. Aggregation inhibition increased relative to the number of carbons in the fatty acids. Moreover, these compounds protected cells against ER stress-induced neuronal cell death. The cytoprotective effect correlated with the in vitro chemical chaperone activity. Similarly, cell viability decreased on treatment with tunicamycin, an ER stress inducer, and was dependent on the number of carbons in the fatty acids. Moreover, the expression of glucose-regulated proteins 94 and 78 (GRP94, 78) decreased according to the number of carbons in the fatty acids. Furthermore, we investigated the effects of these compounds on the accumulation of Pael-R in neuroblastoma cells. 3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R. Overexpressed Pael-R accumulated in the ER of cells. With 3-PPA and 4-PBA treatment, the localization of the overexpressed Pael-R shifted away from the ER to the cytoplasmic membrane. These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.
内容記述
This work was partly supported by a Sasakawa Scientific Research Grant from the Japan Science Society. In addition, this work was supported by Grants-in-Aid for Scientific Research (21590101, 21300142, 20659013, and 21590120) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
掲載誌名
Biological and Pharmaceutical Bulletin
35巻
1号
開始ページ
84
終了ページ
90
出版年月日
2012-10-01
出版者
The Pharmaceutical Society of Japan
ISSN
0918-6158
1347-5215
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
publisher
権利情報
© 2012 The Pharmaceutical Society of Japan
関連情報URL
部局名
医歯薬保健学研究科