Valproate, a mood stabilizer, induces WFS1 expression and modulates its interaction with ER stress protein GRP94
Authors
Kakiuchi, ChihiroIshigaki, Shinsuke
Oslowski, Christine M.
Fonseca, Sonya G.
Kato, Tadafumi
Urano, Fumihiko
Document Type
Journal ArticlePublication Date
2009-01-06Keywords
AnimalsAntimanic Agents
Biological Markers
Bipolar Disorder
Cell Line
Endoplasmic Reticulum
Gene Expression Regulation
Humans
Lithium
Membrane Glycoproteins
Membrane Proteins
Mice
Promoter Regions, Genetic
Stress, Physiological
Valproic Acid
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
BACKGROUND: Valproate is a standard treatment for bipolar disorder and a first-line mood stabilizer. The molecular mechanisms underlying its actions in bipolar disorder are unclear. It has been suggested that the action of valproate is linked to changes in gene expression and induction of endoplasmic reticulum (ER) stress-response proteins. PRINCIPAL FINDINGS: Here we show that valproate modulates the ER stress response through the regulation of WFS1, an important component for mitigating ER stress. Therapeutic concentrations of valproate induce expression of WFS1 mRNA and activate the WFS1 promoter. In addition, WFS1 forms a complex with GRP94, an ER stress-response protein, in which valproate dose-dependently enhances its dissociation from GRP94. CONCLUSIONS: These results suggest that the therapeutic effects of valproate in bipolar disorder may be mediated by WFS1 expression and its dissociation from GRP94.Source
Kakiuchi C, Ishigaki S, Oslowski CM, Fonseca SG, Kato T, et al. (2009) Valproate, a Mood Stabilizer, Induces WFS1 Expression and Modulates Its Interaction with ER Stress Protein GRP94. PLoS ONE 4(1): e4134. doi:10.1371/journal.pone.0004134. Link to article on publisher's siteDOI
10.1371/journal.pone.0004134Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39404PubMed ID
19125190Related Resources
Link to Article in PubMedRights
Copyright: © 2009 Kakiuchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0004134