The role of protein kinase C α and ε isozymes in DNA synthesis induced by muscarinic receptors in a glial cell line

Marina Guizzetti, Min Wei, Lucio G. Costa

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Acetylcholine has been shown to induce proliferation of human astrocytoma cells by activating muscarinic receptors, particularly the m3 subtype. In the present study the role of protein kinase C in DNA synthesis induced by carbachol has been investigated. Carbachol-induced [methyl-3H]thymidine incorporation was inhibited by the protein kinase C inhibitors GF 109203X and staurosporine. However, carbachol-induced DNA synthesis was only partially reduced by protein kinase C down-regulation by phorbol 12-myristate 13-acetate (PMA), and maximal concentrations of carbachol and PMA had an additive effect on [methyl-3H]thymidine incorporation. Exposure for 24 h to maximally effective concentrations of carbachol did not induce down-regulation of protein kinase C α, and caused a small but significant down-regulation of protein kinase C ε; cells exposed for 24 h to carbachol were still able to respond with protein kinase C translocation to PMA stimulation. Carbachol caused a significant increase of phorbol ester binding, but did not stimulate protein kinase C α translocation, while it caused a short-lasting translocation of protein kinase C ε; however, protein kinase C ε translocation was not correlated with the time-course of carbachol-induced increase in [methyl-3H]thymidine incorporation. On the other hand, the time-course of translocation/down-regulation of protein kinase C α and protein kinase C ε induced by PMA was in good correlation with the time-course of PMA-induced [methyl-3H]thymidine incorporation. These results suggest that protein kinase C α may not be involved in DNA synthesis induced by muscarinic receptors stimulation in 132-1N1 astrocytoma cells, while protein kinase C ε appears to play a role in the initial exit from G0/G1 phase, though it cannot be considered the major determinant for sustained proliferation. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)223-233
Number of pages11
JournalEuropean Journal of Pharmacology
Volume359
Issue number2-3
DOIs
StatePublished - Oct 23 1998

Keywords

  • Astrocytoma cell
  • Cell proliferation
  • Muscarinic receptor
  • Protein kinase C

ASJC Scopus subject areas

  • Pharmacology

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