Valproate, a mood stabilizer, induces WFS1 expression and modulates its interaction with ER stress protein GRP94.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 19125190.
- Also identified by DOI 10.1371/journal.pone.0004134 and PMC identifier 2607540.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Antimanic Agents
- Gene Expression Regulation
- Membrane Glycoproteins
- Membrane Proteins
- Valproic Acid