| Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress. | |
| | |
MedLine Citation:
|
PMID: 22223342 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Seisuke Mimori; Yasunobu Okuma; Masayuki Kaneko; Koichi Kawada; Toru Hosoi; Koichiro Ozawa; Yasuyuki Nomura; Hiroshi Hamana |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Biological & pharmaceutical bulletin Volume: 35 ISSN: 1347-5215 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 2012 |
Date Detail:
|
Created Date: 2012-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: Japan |
Other Details:
|
Languages: eng Pagination: 84-90 Citation Subset: IM |
Affiliation:
|
Department of Pharmaceutical Chemistry, Chiba Institute of Science. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibitory Effects of Morinda citrifolia Extract and Its Constituents on Melanogenesis in Murine B16...
Next Document: Roles of Histamine in Exercise-Induced Fatigue: Favouring Endurance and Protecting against Exhaustio...