| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Protective Effects of 4-Phenylbutyrate Derivatives on the Neuronal Cell Death and Endoplasmic Reticulum Stress |
|
言語 |
en |
| 作成者 |
Mimori, Seisuke
Okuma, Yasunobu
Kaneko, Masayuki
Kawada, Koichi
Hosoi, Toru
Ozawa, Koichiro
Nomura, Yasuyuki
Hamana, Hiroshi
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
© 2012 The Pharmaceutical Society of Japan |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
4-phenylbutyrate |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
3-phenylpropionate |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
endoplasmic reticulum stress |
| 主題 |
|
|
主題Scheme |
NDC |
|
主題 |
490 |
| 内容記述 |
|
|
内容記述 |
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. |
|
言語 |
en |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
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. |
| 出版者 |
|
|
出版者 |
The Pharmaceutical Society of Japan |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1248/bpb.35.84 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1248/bpb.35.84 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0918-6158 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1347-5215 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA10885497 |
| 開始ページ |
|
|
開始ページ |
84 |
| 書誌情報 |
Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin
巻 35,
号 1,
p. 84-90,
発行日 2012-10-01
|
| 旧ID |
47058 |
BiolPhamBull_35_84.pdf (9.8 MB)
