Lithium augments fos protoonocogene expression in PC12 pheochromocytoma cells: implications for therapeutic action of lithium

Vasundhara D. Kalasapudi, Giulia Sheftel, Margaret M. Divish, Demitri F. Papolos, Herbert M. Lachman

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

It has been proposed that lithium's antimanic action is due to an effect on phosphoinositide metabolism. Second messengers generated by this pathway regulate calcium mobilization and the activity of the serine and threonine kinase, protein kinase C (PKC). Included among the targets of PKC is activation of fos protooncogene expression, a well-established component of the AP-1 transcription factor. Because of these interactions, we investigated the effect of lithium on fos gene expression in PC12 pheochromocytoma cells. We find that lithium increases the level of fos mRNA that occurs in response to receptor and postreceptor activation of PKC. Treatment with lithium also leads to an augmentation of muscarinic cholinergic-mediated fos gene expression in cells that are down-regulated as a result of excessive cholinergic stimulation. The ability of lithium to enhance the response of a down-regulated cholinergic system suggests a model for its therapeutic efficacy in affective disorders.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalBrain Research
Volume521
Issue number1-2
DOIs
StatePublished - Jun 25 1990

Keywords

  • Carbachol
  • Lithium
  • Manic-depression
  • Muscarinic cholinergic
  • PC12 cell
  • Phosphoinositide
  • Protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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