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 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.
Haddley
Kate
K
School of Biomedical Science, University of Liverpool, Liverpool, Merseyside L69 3GE, UK.
Spencer
Eleanor Mary
EM
Vasiliou
Sylvia Argiroula
SA
Howard
Mark
M
Thippeswamy
Thimmasettappa
T
Bubb
Vivien Jill
VJ
Quinn
John P
JP
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000235:genetics / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism
D018692:Antimanic Agents; D011498:Protein Precursors; D015320:Tachykinins; D051720:Upstream Stimulatory Factors; C497182:Usf1 protein, rat; C497187:Usf2 protein, rat; C044206:preprotachykinin; D013373:Substance P; D018021:Lithium Chloride