Source:http://linkedlifedata.com/resource/pubmed/id/15872096
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
18
|
| pubmed:dateCreated |
2005-5-5
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| pubmed:abstractText |
Increasing data suggest that impairments of cellular plasticity/resilience underlie the pathophysiology of bipolar disorder. A series of microarray studies with validating criteria have recently revealed a common, novel target for the long-term actions of the structurally highly dissimilar mood stabilizers lithium and valproate: BAG-1 [BCL-2 (B-cell CLL/lymphoma 2)-associated athanogene]. Because BAG-1 attenuates glucocorticoid receptor (GR) nuclear translocation, activates ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinases, and potentiates anti-apoptotic functions of BCL-2, extensive additional studies were undertaken. Chronic administration of both agents at therapeutic doses increased the expression of BAG-1 in rat hippocampus. Furthermore, these findings were validated at the protein level, and the effects were seen in a time frame consistent with therapeutic effects and were specific for mood stabilizers. Functional studies showed that either lithium or valproate, at therapeutically relevant levels, inhibited dexamethasone-induced GR nuclear translocation and inhibited GR transcriptional activity. Furthermore, small interfering RNA studies showed that these inhibitory effects on GR activity were mediated, at least in part, through BAG-1. The observation that BAG-1 inhibits glucocorticoid activation suggests that mood stabilizers may counteract the deleterious effects of hypercortisolemia seen in bipolar disorder by upregulating BAG-1. Additionally, these studies suggest that regulation of GR-mediated plasticity may play a role in the treatment of bipolar disorder and raise the possibility that agents affecting BAG-1 more directly may represent novel therapies for this devastating illness.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Antimanic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2-associated athanogene 1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/DAPI,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Lithium,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Valproic Acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
4
|
| pubmed:volume |
25
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4493-502
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15872096-Alkaline Phosphatase,
pubmed-meshheading:15872096-Animals,
pubmed-meshheading:15872096-Antimanic Agents,
pubmed-meshheading:15872096-Behavior, Animal,
pubmed-meshheading:15872096-Blotting, Western,
pubmed-meshheading:15872096-Cell Line, Tumor,
pubmed-meshheading:15872096-DNA-Binding Proteins,
pubmed-meshheading:15872096-Dexamethasone,
pubmed-meshheading:15872096-Dose-Response Relationship, Drug,
pubmed-meshheading:15872096-Drug Interactions,
pubmed-meshheading:15872096-Gene Expression,
pubmed-meshheading:15872096-Hippocampus,
pubmed-meshheading:15872096-Humans,
pubmed-meshheading:15872096-Immunohistochemistry,
pubmed-meshheading:15872096-Indoles,
pubmed-meshheading:15872096-Lithium,
pubmed-meshheading:15872096-Male,
pubmed-meshheading:15872096-Molecular Weight,
pubmed-meshheading:15872096-Neuroblastoma,
pubmed-meshheading:15872096-RNA, Small Interfering,
pubmed-meshheading:15872096-Rats,
pubmed-meshheading:15872096-Rats, Wistar,
pubmed-meshheading:15872096-Receptors, Glucocorticoid,
pubmed-meshheading:15872096-Time Factors,
pubmed-meshheading:15872096-Transcription Factors,
pubmed-meshheading:15872096-Transfection,
pubmed-meshheading:15872096-Valproic Acid
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| pubmed:year |
2005
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| pubmed:articleTitle |
The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers.
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| pubmed:affiliation |
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20852, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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