Neurotrophic factor production in human astrocytoma cells by 2,5,6-tribromogramine via activation of epsilon isoform of protein kinase C

Masaki Saito, Megumi Hori, Yutaro Obara, Yasushi Ohizumi, Satoko Ohkubo, Norimichi Nakahata

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

It is known that astrocytes secrete several neurotrophic factors to promote the survival of neurons. For the treatment of neuronal disorders, low molecular weight compounds inducing neurotrophic factor synthesis are useful, because neurotrophic factors are polypeptides which cannot cross the blood brain barrier. When rat pheochromocytoma (PC-12) cells were cultivated in the medium of human astrocytoma cells (1321N1) treated with 2,5,6-tribromogramine, they differentiated to neuron-like cells possessing neurites, indicating that 2,5,6-tribromogramine released neurotrophic factors from 1321N1 cells. In fact, 2,5,6-tribromogramine increased nerve growth factor (NGF) protein synthesis and secretion through mRNA expression. 2,5,6-Tribromogramine inhibited carbachol-induced phosphoinositide hydrolysis as well as phorbol 12,13-myristate acetate did. The inhibition was recovered by bisindolylmaleimide I (GF109203X), a specific protein kinase C (PKC) inhibitor, indicating that 2,5,6-tribromogramine may activate PKC. The morphological differentiation of PC-12 cells by the medium treated with 2,5,6-tribromogramine was also reduced by GF109203X. 2,5,6-Tribromogramine translocated PKC-ε but not PKC-α or PKC-ζ, to membrane fraction from cytosol fraction. These results indicate that 2,5,6-tribromogramine promotes the synthesis and secretion of neurotrophic factors including NGF in 1321N1 cells via an activation of PKC-ε.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume28
Issue number4
DOIs
Publication statusPublished - 2006 Jul 1

Keywords

  • 1321N1 human astrocytoma cells
  • 2,5,6-Tribromogramine
  • Nerve growth factor
  • Protein kinase C-ε

ASJC Scopus subject areas

  • Pharmaceutical Science

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