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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-2-25
pubmed:abstractText
Disturbances of events associated with intracellular signaling pathways have been suspected of involvement in the development or progression of affective disorders. Often, heterotrimeric G proteins are located at the beginning of these pathways as modulators of extracellular messages. For this reason, messenger RNA expression of three G protein alpha-subunits and of phosphatidylinositol-3 kinase (PI-3 K) regulatory subunit p85 was examined in granulocytes from patients with bipolar or unipolar affective disorder and compared to healthy controls. Messenger RNA expression of the G protein subunit alpha(q) and of p85 was identical in unipolar and bipolar patients and in controls. Furthermore, mRNAs of G protein subunits alpha(s) and alpha(i2) were not different in unipolar patients as compared to healthy controls. Alpha(s) mRNA, however, was markedly increased in bipolar patients. This increase was observed in lithium-treated (more than 12 months) and in unmedicated patients. Elevated levels of alpha(i2) mRNA in unmedicated bipolar patients did not reach statistical significance, whereas mRNA in bipolar patients receiving lithium was significantly above controls. Finally, long-term medication of unipolar patients with lithium had no influence on alpha(i2) mRNA levels. The data reveal elevated mRNA levels of G alpha(s) as a robust feature of bipolar affective disorder. Moreover, despite responsiveness of alpha(i2) gene expression to cAMP-related events, no substantial upregulation of alpha(i2) mRNA was observed in bipolar patients. The lack of alpha(i2) mRNA upregulation, hence, could be an additional abnormality in these patients. Even though lithium was able to reinstate this upregulation, there was no feedback downregulation of alpha(s). This strongly supports the notion of major disturbances of the cAMP signaling system in bipolar illness.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1359-4184
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
512-20
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9857977-Adult, pubmed-meshheading:9857977-Aged, pubmed-meshheading:9857977-Bipolar Disorder, pubmed-meshheading:9857977-DNA Primers, pubmed-meshheading:9857977-Depressive Disorder, pubmed-meshheading:9857977-Female, pubmed-meshheading:9857977-GTP-Binding Protein alpha Subunits, Gs, pubmed-meshheading:9857977-Gene Expression Regulation, pubmed-meshheading:9857977-Humans, pubmed-meshheading:9857977-Lithium, pubmed-meshheading:9857977-Macromolecular Substances, pubmed-meshheading:9857977-Male, pubmed-meshheading:9857977-Middle Aged, pubmed-meshheading:9857977-Models, Biological, pubmed-meshheading:9857977-Neutrophils, pubmed-meshheading:9857977-Phosphatidylinositol 3-Kinases, pubmed-meshheading:9857977-RNA, Messenger, pubmed-meshheading:9857977-Reference Values, pubmed-meshheading:9857977-Restriction Mapping, pubmed-meshheading:9857977-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:9857977-Transcription, Genetic
pubmed:year
1998
pubmed:articleTitle
Abnormal G protein alpha(s) - and alpha(i2)-subunit mRNA expression in bipolar affective disorder.
pubmed:affiliation
Department of Biology II, University of Freiburg, Freiburg i Br, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't