Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy.
Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy.
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DOI：
10.1038/s41598-018-30365-1
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发表时间：
2018-08-07
影响因子：
4.6
通讯作者：
Ferreira JCB
中科院分区：
文献类型：
--
作者：
Campos JC;Baehr LM;Gomes KMS;Bechara LRG;Voltarelli VA;Bozi LHM;Ribeiro MAC;Ferreira ND;Moreira JBN;Brum PC;Bodine SC;Ferreira JCB
蛋白水解活性增加与骨骼肌萎缩广泛相关。然而，升高的蛋白水解也是通过处理细胞毒性蛋白和非功能性细胞器来维持细胞稳态的关键。我们最近证明，运动激活自噬，并重新建立心脏疾病中的蛋白质稳态。在这里，我们的特点是运动对骨骼肌自噬和蛋白质稳态的影响，在大鼠坐骨神经收缩诱导的神经源性肌病模型。神经源性肌病，其特征在于进行性萎缩和收缩力受损，是由自噬相关标志物的积累和对秋水仙碱和氯喹的急性反应性丧失引起的。与对照动物相比，这些变化与受损蛋白质、分子伴侣和促凋亡标记物水平升高相关。在大鼠中使用氯喹（50 mg.kg-1.day-1）或在小鼠中肌肉特异性缺失Atg 7的持续自噬抑制足以损害对照组的肌肉收缩力，但在神经源性肌病中则不然，这表明功能失调的自噬在骨骼肌病理生理学中至关重要。最后，4周的有氧运动训练（中度跑步机运行，5次/周，1小时/天）之前，神经源性肌病改善骨骼肌自噬流量和蛋白质稳态。这些变化之后是备用的肌肉质量和更好的收缩性能。综上所述，我们的研究结果表明，运动在维持骨骼肌蛋白质稳态和减缓神经源性肌病进展方面具有潜在价值。
Increased proteolytic activity has been widely associated with skeletal muscle atrophy. However, elevated proteolysis is also critical for the maintenance of cellular homeostasis by disposing cytotoxic proteins and non-functioning organelles. We recently demonstrated that exercise activates autophagy and re-establishes proteostasis in cardiac diseases. Here, we characterized the impact of exercise on skeletal muscle autophagy and proteostasis in a model of neurogenic myopathy induced by sciatic nerve constriction in rats. Neurogenic myopathy, characterized by progressive atrophy and impaired contractility, was paralleled by accumulation of autophagy-related markers and loss of acute responsiveness to both colchicine and chloroquine. These changes were correlated with elevated levels of damaged proteins, chaperones and pro-apoptotic markers compared to control animals. Sustained autophagy inhibition using chloroquine in rats (50 mg.kg−1.day−1) or muscle-specific deletion of Atg7 in mice was sufficient to impair muscle contractility in control but not in neurogenic myopathy, suggesting that dysfunctional autophagy is critical in skeletal muscle pathophysiology. Finally, 4 weeks of aerobic exercise training (moderate treadmill running, 5x/week, 1 h/day) prior to neurogenic myopathy improved skeletal muscle autophagic flux and proteostasis. These changes were followed by spared muscle mass and better contractility properties. Taken together, our findings suggest the potential value of exercise in maintaining skeletal muscle proteostasis and slowing down the progression of neurogenic myopathy.
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AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
5.3
作者：
Bozi LH;Jannig PR;Rolim N;Voltarelli VA;Dourado PM;Wisløff U;Brum PC
通讯作者：
Brum PC
影响因子：
25
作者：
Antony, JM;van Marle, G;Power, C
通讯作者：
Power, C
影响因子：
10.8
作者：
Gomes, Katia M. S.;Campos, Juliane C.;Ferreira, Julio C. B.
通讯作者：
Ferreira, Julio C. B.
影响因子：
3.3
作者：
Cunha, Telma F.;Bechara, Luiz R. G.;Brum, Patricia C.
通讯作者：
Brum, Patricia C.