The Cholinergic Stimulating Effects of Ciliary Neurotrophic Factor and Leukemia Inhibitory Factor Are Mediated by Protein Kinase C

Christopher Kalberg*, Shau Yu Yung, John A. Kessler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Abstract: The intracellular mechanisms through which two trophic factors, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), regulate cholinergic development were examined in sympathetic neuron cultures. Treatment with CNTF or LIF increased levels of choline acetyltransferase (ChAT) activity by 375 and 350%, respectively. However, in neuronal cultures depleted of protein kinase C (PKC) activity by chronic phorbol ester treatment, neither CNTF nor LIF elevated ChAT activity. Further, the stimulation of ChAT due to increased cell density was not observed in PKC‐depleted sympathetic neurons. The inhibition of CNTF‐stimulated ChAT by phorbol ester occurred in a dose‐dependent manner and chronic phorbol ester treatments did not alter the levels of the catecholamine biosynthetic enzyme tyrosine hydroxylase. Moreover, increased levels of diacylglycerol, an endogenous activator of PKC, were observed in sympathetic neurons treated with CNTF. However, neither CNTF nor LIF stimulated the hydrolysis of phosphatidylinositol 4,5‐bisphosphate. These observations suggest that a common PKC‐dependent pathway, which is independent of phosphatidylinositol 4,5‐bisphosphate hydrolysis, mediates the cholinergic stimulating effects of CNTF, LIF, and cell‐cell contact in cultured sympathetic neurons.

Original languageEnglish (US)
Pages (from-to)145-152
Number of pages8
JournalJournal of neurochemistry
Volume60
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • Choline acetyltransferase
  • Ciliary neurotrophic factor
  • Leukemia inhibitory factor
  • Protein kinase C
  • Sympathetic neuron
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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