AMP N1-oxide potentiates astrogenesis by cultured neural stem/progenitor cells through STAT3 activation.
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.
Hattori
Noriko
N
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan.
Nomoto
Hiroshi
H
Fukumitsu
Hidefumi
H
Mishima
Satoshi
S
Furukawa
Shoei
S
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
C511284:AMP N1-oxide; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D000249:Adenosine Monophosphate