Division of Cardiology, Department of Medicine, University of California San Diego , La Jolla, California.
Cardiology Section, Department of Medicine, Veterans Administration Healthcare , San Diego, California.
Physiol Genomics. 2018 Sep 1;50(9):746-757. doi: 10.1152/physiolgenomics.00043.2018. Epub 2018 Jun 29.
Immobilization, bed rest, or denervation leads to muscle disuse and subsequent skeletal muscle atrophy. Muscle atrophy can also occur as a component of various chronic diseases such as cancer, AIDS, sepsis, diabetes, and chronic heart failure or as a direct result of genetic muscle disorders. In addition to this atrophic loss of muscle mass, metabolic deregulation of muscle also occurs. In contrast, physical exercise plays a beneficial role in counteracting disuse-induced atrophy by increasing muscle mass and strength. Along with this, exercise can also reduce mitochondrial dysfunction and metabolic deregulation. Still, while exercise causes valuable metabolic and functional adaptations in skeletal muscle, the mechanisms and effectors that lead to these changes such as increased mitochondria content or enhanced protein synthesis are not fully understood. Therefore, mechanistic insights may ultimately provide novel ways to treat disuse induced atrophy and metabolic deregulation. Mass spectrometry (MS)-based proteomics offers enormous promise for investigating the molecular mechanisms underlying disuse and exercise-induced changes in skeletal muscle. This review will focus on initial findings uncovered by using proteomics approaches with human skeletal muscle specimens and discuss their potential for the future study.
固定、卧床休息或去神经支配会导致肌肉废用和随后的骨骼肌萎缩。肌肉萎缩也可能是各种慢性疾病的组成部分,如癌症、艾滋病、败血症、糖尿病和慢性心力衰竭,或直接由遗传性肌肉疾病引起。除了这种肌肉质量的萎缩性损失外,肌肉的代谢失调也会发生。相比之下,体育锻炼通过增加肌肉质量和力量对对抗废用性萎缩起到有益的作用。除此之外,运动还可以减少线粒体功能障碍和代谢失调。尽管如此,虽然运动引起了骨骼肌有价值的代谢和功能适应性,但导致这些变化的机制和效应物,如增加线粒体含量或增强蛋白质合成,尚未完全理解。因此,对机制的深入了解可能最终为治疗废用性萎缩和代谢失调提供新的途径。基于质谱(MS)的蛋白质组学为研究骨骼肌废用和运动诱导变化的分子机制提供了巨大的潜力。本综述将重点介绍使用蛋白质组学方法研究人类骨骼肌标本所揭示的初步发现,并讨论其在未来研究中的潜力。