Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells

Jiro Takito, Junko Kimura, Koji Kajima, Nobuyuki Uozumi, Makoto Watanabe, Akihito Yokosuka, Yoshihiro Mimaki, Masanori Nakamura, Yasushi Ohizumi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

Original languageEnglish
Pages (from-to)728-733
Number of pages6
JournalCanadian Journal of Physiology and Pharmacology
Volume94
Issue number7
DOIs
Publication statusPublished - 2016 Feb 12

Keywords

  • Alzheimer disease
  • CRE-dependent transcription
  • Flavone
  • Nerve growth factor
  • Neuron
  • Nobiletin
  • PC12 cells

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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