Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway
Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway
复制标题
运动通过 AMPK-SIRT1-TFEB 通路激活大脑中的溶酶体功能
DOI：
10.1111/cns.13114
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发表时间：
2019-06-01
影响因子：
5.5
通讯作者：
Lin, Fang
中科院分区：
文献类型：
--
作者：
Huang, Jun;Wang, Xue;Lin, Fang
目的研究运动对溶酶体功能的影响。方法建立小鼠运动模型，以18 rpm（14：00-17：00）的速度进行跑轮运动，5d/wk，连续8周。给小鼠注射EX 527以抑制SIRT 1活性。Western blot和免疫荧光组织化学检测蛋白质水平。透射电镜观察溶酶体和线粒体结构。结果运动促进了TFEB在大脑皮层的核转位，上调了自噬和溶酶体相关基因的转录。运动通过上调AMPK-SIRT 1信号直接激活自噬/溶酶体系统。SIRT 1抑制剂EX 527降低了TFEB调节的基因转录，但对TFEB的核转位几乎没有影响。此外，与短期运动和海藻糖（mTOR非依赖性途径中的经典自噬激活剂）相比，长期运动对溶酶体生物合成的激活作用更显著。结论跑步运动通过AMPK-SIRT 1-TFEB途径激活脑内溶酶体功能。
Aim To study the effects of exercise on lysosomal functions. Methods Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00-17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluorescence histochemistry. The transmission electron microscopic examination was used to show the structure of lysosome and mitochondria. Results Exercise promoted the nuclear translocation of TFEB in the cortex which upregulated the transcription of genes associated with autophagy and lysosome. Exercise directly activated autophagy/lysosome system via up-regulating of AMPK-SIRT1 signaling. The SIRT1 inhibitor EX527 decreased TFEB regulated gene transcription but had little effect on the nuclear translocation of TFEB. In addition, long-term exercise showed more significant effects on activation of lysosomes biogenesis compared with the short-term exercise and trehalose, a classical autophagy activator in the mTOR-independent pathway. Conclusion Running exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway.