Linked Life Data

11723174

Source:http://linkedlifedata.com/resource/pubmed/id/11723174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-11-27
pubmed:abstractText
The gene (Macs) for the mouse myristoylated alanine-rich C kinase substrate (MARCKS) encodes a prominent substrate for protein kinase C that has been implicated in processes requiring signal dependent changes in actin-membrane plasticity and cytoskeletal restructuring. We have previously demonstrated that MARCKS protein is significantly down-regulated in rat hippocampus and in an immortalized hippocampal cell line (HN33.dw) following long-term exposure to lithium at clinically relevant concentrations (1 mM). Our current studies have examined transcriptional and post-transcriptional events that may underlie the lithium-induced down-regulation of MARCKS protein in the cultured hippocampal cell model system. MARCKS mRNA and protein expression were found to be concomitantly down-regulated following exposure of the HN33.dw cells to chronic lithium. Whereas the stability of MARCKS mRNA remained unchanged in the presence of lithium, nuclear run-off assay indicated that the transcription of nascent MARCKS mRNA was significantly reduced (approximately 50%) in the cells that had been treated with lithium for 7 days. Transient transfection of HN33.dw cells with a mouse cloned Macs promoter (993-bp) showed that the Macs promoter activity was attenuated to the same extent after chronic (7-10 days), but not subacute (24 h), lithium exposure. The inhibition of the Macs promoter was found to be dependent upon the presence of a 280-bp promoter region between -993-bp and -713-bp relative to the translation start site, suggesting that this region is a potential lithium-responsive region of Macs promoter (LRR). Mutant promoter lacking the LRR not only did not respond to chronic lithium exposure but also had significantly reduced promoter activity, suggesting that chronic lithium exposure represses the transcriptional activity of activator(s) bound to the promoter. Taken together, our data indicate that transcriptional inhibition of the Macs gene underlies the lithium-induced down-regulation of MARCKS expression in the immortalized hippocampal cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
816-25
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11723174-Animals, pubmed-meshheading:11723174-Cell Line, pubmed-meshheading:11723174-Down-Regulation, pubmed-meshheading:11723174-Gene Expression Regulation, pubmed-meshheading:11723174-Genes, Regulator, pubmed-meshheading:11723174-Hippocampus, pubmed-meshheading:11723174-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11723174-Lithium, pubmed-meshheading:11723174-Membrane Proteins, pubmed-meshheading:11723174-Mice, pubmed-meshheading:11723174-Mutagenesis, Site-Directed, pubmed-meshheading:11723174-Promoter Regions, Genetic, pubmed-meshheading:11723174-Proteins, pubmed-meshheading:11723174-RNA, Messenger, pubmed-meshheading:11723174-RNA Stability, pubmed-meshheading:11723174-Transcription, Genetic, pubmed-meshheading:11723174-Transcriptional Activation
pubmed:year
2001
pubmed:articleTitle
Transcriptional down-regulation of MARCKS gene expression in immortalized hippocampal cells by lithium.
pubmed:affiliation
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.