Involvement of protein kinase C in Ca2+ -signaling pathways to activation of AP-1 DNA-binding activity evoked via NMDA- and voltage-gated Ca2+ channels

Ken Ichi Ohtani, Hiroaki Sakurai, Esther Oh, Emi Iwata, Tomofusa Tsuchiya, Masaaki Tsuda

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Stimulation of cultured cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein-1 (AP-1) DNA-binding activity, which can be monitored by an increase in 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive element (TRE)-binding activity, in concert with c-fos induction. For this increase in TRE-binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA-AM, abolished this increase. Close correspondence between the dose-response curves of 45Ca2+ uptake and TRE-binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca2+-signaling processes leading to the increase in TRE-binding activity, but also controlled its increased level. Stimulation of non-NMDA receptors by KA mainly caused Ca2+ influx through voltage-gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA-gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE-binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down-regulation of PKC inhibited the increase in TRE-binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca2+-signaling pathways for the increase in TRE-binding activity coupled with the activation of NMDA- and non-NMDA receptors.

Original languageEnglish (US)
Pages (from-to)605-614
Number of pages10
JournalJournal of Neurochemistry
Volume65
Issue number2
StatePublished - Aug 1995
Externally publishedYes

Keywords

  • AP-1
  • Ca influx
  • Cerebellar granule cells
  • Glutamate receptors
  • Protein kinase C
  • c-fos induction

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

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