Lithium attenuates nerve growth factor-induced activation of AP-1 DNA binding activity in PC12 cells

M. Tino Unlap, Richard S. Jope

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

This investigation tested if lithium, the primary therapeutic agent for bipolar mood disorder, modulated activation of the AP-1 transcription factor in PC12 cells treated with nerve growth factor (NGF), which induces robust responses in these cells. NGF induced large, time-dependent increases in AP-1 DNA binding activity. Pretreatment with 5 mmol/L lithium for 24 h reduced AP-1 induction by NGF by 42%; shorter treatments and lower concentrations of lithium had smaller inhibitory effects on AP-1. This effect of lithium was not limited to AP-1, as it also inhibited NGF-induced cyclic AMP responsive element (CRE) DNA binding activity. In contrast, activation of AP-1 and CRE by forskolin was unaffected by lithium. AP-1 constituent proteins were differentially susceptible to lithium, as cJun was reduced by 55%, cFos was unaffected by lithium, and an intermediate effect was observed with Jun B. These results reveal that lithium modulates the activation of transcription factors in a neuronal cell model, indicating that selective regulation of gene expression may contribute to the long term in vivo effect of lithium.

Original languageEnglish (US)
Pages (from-to)12-17
Number of pages6
JournalNeuropsychopharmacology
Volume17
Issue number1
DOIs
StatePublished - Jul 1997
Externally publishedYes

Keywords

  • AP-1
  • Bipolar disorder
  • CRE
  • Fos
  • Immediate early genes
  • Jun
  • Lithium

ASJC Scopus subject areas

  • Pharmacology

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