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

机译:AMP N1氧化物通过STAT3激活增强培养的神经干/祖细胞的星形胶质细胞生成

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摘要

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 μM) 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.
机译:我们较早地确定了腺苷一磷酸(AMP)N1-氧化物是蜂王浆(RJ)的一种独特化合物,该化合物可诱导培养的大鼠嗜铬细胞瘤PC12细胞中的神经突生长。在本研究中,研究了AMP N1-氧化物对培养的神经干/祖细胞(NSC)增殖和/或分化的影响。对于细胞增殖,低微摩尔浓度的AMP N1-氧化物或其母体化合物AMP同样增强了碱性成纤维细胞生长因子(FGF-2)诱导NSC增殖的活性,尽管单独测试的两种化合物都不影响细胞增殖。相反,即使存在FGF-2,高浓度的AMP N1-氧化物(超过20μM)也显着抑制细胞生长。但是,使用AMP并没有观察到这种抑制作用。至于细胞分化,当在缺乏FGF-2的培养基中培养细胞时,AMP N1-氧化物而非AMP以剂量依赖性方式增加星形胶质细胞的产生。神经元或少突胶质细胞的生成不受AMP N1氧化物的影响。此外,AMP N1-氧化物增加了STAT3(信号转导和转录激活因子3)的磷酸化,STAT3是介导星形胶质细胞特异性基因表达的转录因子。这些结果表明,AMP N1-氧化物是通过激活STAT3促进NSC星形胶质形成的成分之一。

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