Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization.
Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization.
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DOI：
10.1016/j.expneurol.2013.01.005
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Cohn, Ronald D
中科院分区：
文献类型：
--
作者：
Xu, Ran;Andres-Mateos, Eva;Mejias, Rebeca;MacDonald, Elizabeth M;Leinwand, Leslie A;Merriman, Dana K;Fink, Rainer H A;Cohn, Ronald D
骨骼肌萎缩是许多废用性疾病中非常常见的临床挑战。维持肌肉质量对于对抗这些临床病症引起的衰弱功能后果至关重要。相反，冬眠代表一种生理状态，在这种状态下，尽管长时间的固定和缺乏营养摄入，但仍有天然的保护作用，防止废用性萎缩。尽管过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子1-α（PGC-1α）是肌肉重塑途径中的中心介质，但其在冬眠期间骨骼肌质量保存中的作用仍不清楚。由于PGC-1α调节肌纤维类型形成和线粒体生物发生，我们分析了13线地松鼠的肌肉。我们发现，动物在麻木表现出一个转变，以慢收缩I型肌纤维。这种转换伴随着PGC-1α介导的耐力运动途径的激活。此外，我们观察到抗氧化能力增强，但没有氧化应激的证据，细胞凋亡易感性显着下降，线粒体丰度和代谢增强。这些结果表明，激活的耐力运动通路可以在体内实现，尽管长时间的固定，因此可能是一个重要的机制，骨骼肌保存在冬眠期间。这种PGC-1α调节途径可能是促进骨骼肌稳态和氧化平衡的潜在治疗靶点，以防止各种遗传性和获得性神经肌肉疾病条件下的肌肉损失。
Skeletal muscle atrophy is a very common clinical challenge in many disuse conditions. Maintenance of muscle mass is crucial to combat debilitating functional consequences evoked from these clinical conditions. In contrast, hibernation represents a physiological state in which there is natural protection against disuse atrophy despite prolonged periods of immobilization and lack of nutrient intake. Even though peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1-α (PGC-1α) is a central mediator in muscle remodeling pathways, its role in the preservation of skeletal muscle mass during hibernation remains unclear. Since PGC-1α regulates muscle fiber type formation and mitochondrial biogenesis, we analyzed muscles of 13-lined ground squirrels. We find that animals in torpor exhibit a shift to slow-twitch Type I muscle fibers. This switch is accompanied by activation of the PGC-1α-mediated endurance exercise pathway. In addition, we observe increased antioxidant capacity without evidence of oxidative stress, a marked decline in apoptotic susceptibility, and enhanced mitochondrial abundance and metabolism. These results show that activation of the endurance exercise pathway can be achieved in vivo despite prolonged periods of immobilization, and therefore might be an important mechanism for skeletal muscle preservation during hibernation. This PGC-1α regulated pathway may be a potential therapeutic target promoting skeletal muscle homeostasis and oxidative balance to prevent muscle loss in a variety of inherited and acquired neuromuscular disease conditions.