Ethanol inhibits muscarinic receptor-mediated DNA synthesis and signal transduction in human fetal astrocytes

Marina Guizzetti, Thomas Möller, Lucio G. Costa

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

We previously found that ethanol inhibits muscarinic receptor-induced proliferation of rat cortical astrocytes and human astrocytoma cells and suggested this as a possible mechanism involved in its developmental neurotoxicity. We also observed that, though several signal transduction pathways are relevant for carbachol-induced cell proliferation, activation of PKC ζ and p70S6 kinase is selectively inhibited by low concentrations of ethanol. In the present study we used fetal human astrocytes to expand these findings to a direct target of ethanol in humans. Astrocyte cultures, deriving from legally aborted fetuses, were stained for GFAP and shown to be 90-95% pure. Carbachol induced increases in [3H]thymidine and BrdU incorporation in synchronized cells. Carbachol-induced DNA synthesis was strongly inhibited by ethanol. Carbachol also induced phosphorylation of (Thr410)PKC ζ, (Ser473)Akt, and (Thr389)p70S6 kinase, and ethanol (50 mM) inhibited phosphorylation of PKC ζ and p70S6 kinase, but not of Akt. These results expand previous findings in rat astrocytes and human astrocytoma cells and suggest that intracellular signal transduction pathways activated by muscarinic receptors may represent a relevant target for the developmental neurotoxicity of ethanol in humans.

Original languageEnglish (US)
Pages (from-to)68-70
Number of pages3
JournalNeuroscience Letters
Volume344
Issue number1
DOIs
StatePublished - Jun 19 2003

Keywords

  • Carbachol
  • Cell proliferation
  • Ethanol
  • Human fetal astrocytes
  • Muscarinic receptors
  • PKC ζ
  • p70S6 kinase

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Ethanol inhibits muscarinic receptor-mediated DNA synthesis and signal transduction in human fetal astrocytes'. Together they form a unique fingerprint.

  • Cite this