O-GlcNAc糖基化通过Akt/AMPK/mTOR信号通路参与冬眠达乌尔黄鼠抗废用性肌萎缩的机制研究

冬眠动物抗废用性肌萎缩的发生机制是生理生态学领域亟待研究的重要课题。Akt/AMPK/mTOR信号通路通过调节蛋白质合成，调控骨骼肌萎缩的发生，而O-GlcNAc糖基化可调节Akt和AMPK活性。申请者研究发现冬眠达乌尔黄鼠骨骼肌蛋白的O-GlcNAc糖基化水平上调，同时AKT和mTOR磷酸化水平升高，AMPK磷酸化水平下降。因此提出：O-GlcNAc糖基化可能通过调节Akt/AMPK/mTOR信号通路在黄鼠抗废用性肌萎缩中起重要作用。本项目拟研究在冬眠黄鼠抗废用性肌萎缩中：(1)O-GlcNAc转移酶、O-GlcNAc糖苷酶表达的变化；(2)O-GlcNAc糖基化上调和下调对骨骼肌的影响；(3)O-GlcNAc糖基化的变化对Akt/AMPK/mTOR信号通路的影响。为深入理解冬眠动物抗废用性肌萎缩的发生机制提供理论与实验依据，为人类废用性肌萎缩防治措施的研发提供新思路。

The mechanism of muscle disuse atrophy resistance in hibernators is important to clarify in the field of physiological ecology. Akt/AMPK/mTOR signaling pathway regulates skeletal muscle atrophy by regulating protein synthesis, while O-GlcNAcylation can regulate Akt and AMPK activities. Our studies showed that the O-GlcNAcylation levels of proteins were upregulated in hibernating Daurian ground squirrels (Spermophilus dauricus). Meanwhile the phosphorylation levels Akt and mTOR were increased, and the phosphorylation level of AMPK was decreased. Therefore, we propose that O-GlcNAcylation may play a key role in in mechanism of muscle disuse atrophy resistance in hibernating Daurian ground squirrels through regulating Akt/AMPK/mTOR signaling pathway. Based on the previous research, this project will further investigate the following content in muscle disuse atrophy resistance in hibernating Daurian ground squirrels: (1) the changes of expressions of O-GlcNAc transferase and O-GlcNAcase ; (2) the effects of upregulation and downregulation of O-GlcNAcylation on skeletal muscles; (3) the effects of changes in O-GlcNAcylation levels on Akt/AMPK/mTOR signaling pathway. The objective of this project is to provide some new theoretical and experimental evidences for deeply understanding the mechanisms counteracting disuse muscle atrophy in hibernators and to provide insights into possible approaches to prevent and treat disuse muscle atrophy in human.