Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1999-3-2
|
| pubmed:abstractText |
Valproic acid (VPA) is a potent broad spectrum anticonvulsant with demonstrated efficacy in the treatment of Bipolar Affective Disorder, but the biochemical basis for VPA's antimanic or mood-stabilizing actions have not been fully elucidated. It has been demonstrated that VPA, at therapeutically relevant concentrations, increases AP-1 DNA binding activity in cultured cells in vitro. These findings raise the possibility that VPA may produce its mood-stabilizing effects by regulating the expression of subsets of genes via its effects on the AP-1 family of transcription factors. To determine if VPA does, in fact, enhance AP-1 mediated gene expression, the effects of VPA on the expression of a luciferase reporter gene were studied in transiently transfected rat C6 glioma and human SH-SY5Y neuroblastoma cells using the pGL2-control vector. The luciferase gene in the vector is driven by an SV40 promoter which contains well characterized AP-1 sites. VPA produced a greater than doubling of luciferase activity in a time- and concentration-dependent manner in both cell lines. Furthermore, mutations of the AP-1 sites in the SV40 promoter markedly attenuated the VPA-induced increases in luciferase activity. These effects of VPA on AP-1 mediated gene expression are very similar to the effects observed with lithium, and suggest that the temporal regulation of AP-1 mediated gene expression in critical neuronal circuits may play a role in the long-term therapeutic efficacy of these agents.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticonvulsants,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Valproic Acid
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0169-328X
|
| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 1999 Elsevier Science B.V.
|
| pubmed:issnType |
Print
|
| pubmed:day |
22
|
| pubmed:volume |
64
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
52-8
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9889318-Animals,
pubmed-meshheading:9889318-Anticonvulsants,
pubmed-meshheading:9889318-Bipolar Disorder,
pubmed-meshheading:9889318-DNA-Binding Proteins,
pubmed-meshheading:9889318-Gene Expression Regulation,
pubmed-meshheading:9889318-Genes, Reporter,
pubmed-meshheading:9889318-Glioma,
pubmed-meshheading:9889318-Humans,
pubmed-meshheading:9889318-Luciferases,
pubmed-meshheading:9889318-Molecular Sequence Data,
pubmed-meshheading:9889318-Mutation,
pubmed-meshheading:9889318-Neuroblastoma,
pubmed-meshheading:9889318-Neurons,
pubmed-meshheading:9889318-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:9889318-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:9889318-Rats,
pubmed-meshheading:9889318-Sequence Homology, Amino Acid,
pubmed-meshheading:9889318-Transcription Factor AP-1,
pubmed-meshheading:9889318-Transfection,
pubmed-meshheading:9889318-Tumor Cells, Cultured,
pubmed-meshheading:9889318-Valproic Acid
|
| pubmed:year |
1999
|
| pubmed:articleTitle |
Valproate robustly enhances AP-1 mediated gene expression.
|
| pubmed:affiliation |
Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, WSU School of Medicine, 2301 Scott Hall, 540 E. Canfield Avenue, Detroit, MI 48201, USA. gchen@med.wayne.edu
|
| pubmed:publicationType |
Journal Article
|