AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun
AMPK Negatively Regulates Peripheral Myelination via Activation of c-Jun
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AMPK 通过激活 c-Jun 负向调节外周髓鞘形成
DOI：
10.1007/s12035-016-9913-3
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发表时间：
2017-07-01
影响因子：
5.1
通讯作者：
Sun, Cheng
中科院分区：
文献类型：
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作者：
Liu, Xiaoyu;Peng, Su;Sun, Cheng
雪旺细胞（SC）在轴突周围形成鞘的过程称为髓鞘形成，其在周围神经系统（PNS）的正常生理功能中起着关键作用。PNS中调节SC髓鞘形成的分子机制仍有待阐明。在这里，我们表明，在坐骨神经中的AMP激活的蛋白激酶（AMPK）在PNS髓鞘形成过程中逐渐减少。药理学干预表明，AICAR激活AMPK可减弱SC中的髓鞘基因表达，而化合物C（ComC）抑制AMPK或AMPKα1敲低可刺激髓鞘基因表达。随后的实验表明，在SC中，AMPK激活了PNS髓鞘形成的负调节剂c-Jun。新生大鼠应用ComC可显著下调坐骨神经c-Jun表达。ComC可明显促进坐骨神经脂质和蛋白质的合成。因此，髓鞘基因表达的坐骨神经，以及髓鞘厚度，促进在ComC处理的大鼠。总之，我们的数据确定AMPK是PNS中雪旺细胞髓鞘形成的重要负调节因子，并且这种调节作用可能依赖于c-Jun激活。
The process of Schwann cells (SCs) forming a sheath around axons is termed as myelination, which plays a pivotal role for proper physiological function in the peripheral nervous system (PNS). The molecular mechanisms regulating SC myelination in the PNS remain to be elucidated. Here, we show that AMP-activated protein kinase (AMPK) in sciatic nerves was gradually decreased during the PNS myelination process. Pharmacological interventions showed that activation of AMPK by AICAR attenuated myelin gene expression in SCs, whereas inhibition of AMPK by Compound C (ComC) or AMPKα1 knockdown stimulated myelin gene expression. Following experiments revealed that c-Jun, a negative modulator of PNS myelination, was activated by AMPK in SCs. The application of ComC in newborn rats markedly downregulated c-Jun expression in sciatic nerves. The lipid and protein synthesis in sciatic nerves was greatly potentiated by ComC. As a consequence, myelin gene expression in sciatic nerves, as well as myelin sheath thickness, were promoted in the ComC-treated rats. All together, our data identify that AMPK is an important negative regulator of Schwann cell myelination in the PNS, and this regulation role may rely on c-Jun activation.