Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells.
Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells.
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磷酸果糖激酶-1 负向调节神经干细胞的神经发生
DOI：
10.1007/s12264-016-0032-y
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Zhu Dongya
中科院分区：
文献类型：
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作者：
Zhang Fengyun;Qian Xiaodan;Qin Cheng;Lin Yuhui;Wu Haiyin;Chang Lei;Luo Chunxia;Zhu Dongya
磷酸果糖激酶-1 （PFK-1）是一种主要的调节糖酵解酶，与星形胶质细胞和神经元的功能有关。在这里，我们报道了PFK-1通过靶向前神经转录因子负调控神经干细胞（NSCs）的神经发生。通过体外检测，我们发现PFK-1敲低增强，PFK-1过表达抑制NSCs的神经元分化，这与缺氧5h NSCs的结果一致。同时，PFK-1敲低诱导的神经发生归因于神经祖细胞增殖增加和NSCs对神经元谱系的承诺。同样，体内PFK-1的下调也增加了海马齿状回的神经发生。最后，我们证明了PFK-1介导的神经发生可能是通过靶向哺乳动物棘皮-鳞片同源物-1 （Mash 1）、神经元分化因子（NeuroD）和与性别决定区Y （SRY）相关的HMG盒子2 （Sox2）来实现的。综上所述，我们的结果表明PFK-1是神经发生的重要调节因子。
Phosphofructokinase-1 (PFK-1), a major regulatory glycolytic enzyme, has been implicated in the functions of astrocytes and neurons. Here, we report that PFK-1 negatively regulates neurogenesis from neural stem cells (NSCs) by targeting pro-neural transcriptional factors. Usingin vitroassays, we found that PFK-1 knockdown enhanced, and PFK-1 overexpression inhibited the neuronal differentiation of NSCs, which was consistent with the findings from NSCs subjected to 5 h of hypoxia. Meanwhile, the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage. Similarly,in vivoknockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus. Finally, we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1 (Mash 1), neuronal differentiation factor (NeuroD), and sex-determining region Y (SRY)-related HMG box 2 (Sox2). All together, our results reveal PFK-1 as an important regulator of neurogenesis.