Lithium Chloride Regulation of the Substance P Encoding Preprotachykinin A, Tac1 Gene in Rat Hippocampal Primary Cells

In rat hippocampal cultures, the preprotachykinin A (PPTA/Tac1) gene, which encodes the neuropeptide substance P, is regulated by the action of lithium. We used reporter gene and expression constructs to demonstrate that this mechanism of action of lithium is mediated via a previously characterised...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2011-10, Vol.45 (2), p.94-100
Main Authors: Haddley, Kate, Spencer, Eleanor Mary, Vasiliou, Sylvia Argiroula, Howard, Mark, Thippeswamy, Thimmasettappa, Bubb, Vivien Jill, Quinn, John P.
Format: Article
Language:English
Subjects:
Animals
Antimanic Agents - pharmacology
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell culture
Cells, Cultured
Chloride
Data processing
Gene expression
Gene Expression Regulation
Genes, Reporter
Helix-Loop-Helix Motifs - genetics
Helix-loop-helix proteins
Hippocampus
Hippocampus - cytology
Humans
Lithium
Lithium chloride
Lithium Chloride - pharmacology
Male
Nervous system
Neurochemistry
Neurology
Neuropeptides
Neurosciences
Promoter Regions, Genetic
Promoters
Protein Precursors - genetics
Protein Precursors - metabolism
Proteomics
Rats
Rats, Wistar
Reporter gene
Substance P
Substance P - genetics
Substance P - metabolism
Tachykinins - genetics
Tachykinins - metabolism
Transcription factors
upstream stimulatory factor
Upstream Stimulatory Factors - genetics
Upstream Stimulatory Factors - metabolism
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Summary:In rat hippocampal cultures, the preprotachykinin A (PPTA/Tac1) gene, which encodes the neuropeptide substance P, is regulated by the action of lithium. We used reporter gene and expression constructs to demonstrate that this mechanism of action of lithium is mediated via a previously characterised cis-regulatory Ebox element in the proximal promoter, which binds members of the basic Helix-Loop-Helix family of transcription factors. Consistent with this, in hippocampal cells, both the expression of the endogenous gene and the function of this promoter element are differentially regulated by the basic Helix-Loop-Helix factors, upstream stimulatory factor 1 and 2 (USF1/2). In addition, the genes for USF1 and USF2 are differentially regulated by lithium in these cells. Our data implicate USF1 as a major regulator of the action of lithium on the proximal PPTA promoter.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-010-9431-0