AMP N1-oxide potentiates astrogenesis by cultured neural stem/progenitor cells through STAT3 activation

Biomed Res. 2007 Dec;28(6):295-9. doi: 10.2220/biomedres.28.295.

Abstract

We earlier identified adenosine monophosphate (AMP) N1-oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth from cultured rat pheochromocytoma PC12 cells. In the present study, the effects of AMP N1-oxide on the proliferation and/or differentiation of cultured neural stem/progenitor cells (NSCs) were examined. As for cell proliferation, low micromolar concentrations of AMP N1-oxide or its parent compound, AMP, similarly enhanced the NSC proliferation-inducing activity of basic fibroblast growth factor (FGF-2), although neither compound tested alone affected cell proliferation. Conversely, high concentrations of AMP N1-oxide (over 20 microM) markedly suppressed cell growth even in the presence of FGF-2. However, this suppression was not observed with AMP. As for cell differentiation, AMP N1-oxide, but not AMP, increased the generation of astrocytes in a dose-dependent manner when the cells were cultured in medium lacking FGF-2. The generation of neurons or oligodendrocytes was not influenced by AMP N1-oxide. Furthermore, AMP N1-oxide increased the phosphorylation of STAT3 (signal transducer and activator of transcription 3), a transcription factor that mediates the expression of astrocytespecific genes. These results suggest that AMP N1-oxide is one of the components that facilitates astrogenesis by NSCs through activation of STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacology
  • Adenosine Monophosphate / physiology
  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • AMP N1-oxide
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Adenosine Monophosphate