Mitsugumin 53 promotes mitochondrial autophagy through regulating Ambra1 expression in C2C12 myoblast cells
Mitsugumin 53 promotes mitochondrial autophagy through regulating Ambra1 expression in C2C12 myoblast cells
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DOI：
10.1002/cbin.11097
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发表时间：
2019-03-01
影响因子：
3.9
通讯作者：
Yuan Weijie
中科院分区：
文献类型：
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作者：
Gu Lijie;Zhang Yueyue;Yuan Weijie
本研究旨在探讨Mitsugumin 53（MG 53）在调节骨骼肌细胞线粒体自噬中的作用，并探讨其在慢性肾脏病（CKD）大鼠骨骼肌萎缩防治中的潜在应用。检测5/6肾切除大鼠骨骼肌中自噬beclin 1 regulator 1（Ambra 1）和MG 53的表达，并通过体外实验研究MG 53对C2 C12成肌细胞线粒体自噬的影响。我们的研究结果显示Ambra 1和MG 53在CKD大鼠骨骼肌中的表达显著降低。体外实验表明，MG 53过表达可促进C2 C12细胞Ambra 1的表达和线粒体自噬，提示通过MG 53干预恢复自噬可能有助于清除异常线粒体，缓解肌肉萎缩。结论：CKD大鼠受损或功能不全的线粒体不能被有效清除，这可能与Ambra 1活性低下有关。体外实验表明，MG 53过表达可促进C2 C12细胞Ambra 1的表达，恢复线粒体自噬。MG 53是否能帮助清除异常线粒体，缓解CKD引起的肌肉萎缩，还需进一步研究。
In this study, we investigated the function of Mitsugumin 53 (MG53) in regulation of mitochondrial autophagy in skeletal muscle cells and explored its potential application in the prevention and treatment of skeletal muscle atrophy in rats with chronic kidney disease (CKD). The expression of autophagy beclin 1 regulator 1 (Ambra1) and MG53 in skeletal muscles of 5/6 nephrectomized rats was measured, and the effect of MG53 on mitochondrial autophagy of C2C12 myoblasts was investigated by in vitro experiments. Our results show the expression of Ambra1 and MG53 in the skeletal muscle of CKD rats was significantly decreased. In vitro experiments showed that MG53 overexpression could promote the expression of Ambra1 and mitochondrial autophagy in C2C12 cells, suggesting that recovery of autophagy by MG53 intervention may help remove abnormal mitochondria and alleviate muscle atrophy. In conclusion, the damaged or functionally incomplete mitochondria in CKD rats could not be effectively removed, which may be related to the low activity of Ambra1. In vitro experiments showed that MG53 overexpression could promote the expression of Ambra1 in C2C12 cells and restore mitochondrial autophagy. Whether MG53 can help remove abnormal mitochondria and relieve CKD-induced muscle atrophy requires further study.