CIAFEL, Faculty of Sports Sciences, University of Porto, Porto, Portugal.
Eur J Appl Physiol. 2009 Nov;107(5):553-63. doi: 10.1007/s00421-009-1151-1. Epub 2009 Aug 19.
The aim of this study was to investigate the temporal involvement of different proteolytic systems and muscle proteome changes during experimental disuse atrophy (up to 1 week hindlimb suspension, HS) in murine gastrocnemius muscle. The results showed that proteolysis, cytoprotection mechanisms and signs of cellular infiltration occurred very early. After 1 day of HS, signals of lysosomal activation, rather than programmed cell death (apoptosis), seem to trigger protein breakdown in the whole skeletal muscle. Moreover, the ubiquitin-proteasome pathway remained elevated later whereas all other proteolytic parameters returned to control values when atrophy was fully established. Using proteomics, evidence is provided for metabolic alterations toward glycolysis and for cytoskeleton remodelling suggestive of reduced capacity for force generation. Overall, our data highlight an early and coordinated time-dependent activation of proteolysis, which explains the global proteome alterations observed in gastrocnemius under atrophic conditions.
本研究旨在探讨不同蛋白水解系统在实验性废用性萎缩（至 1 周后肢悬吊，HS）过程中的时间相关性，以及鼠腓肠肌肌肉蛋白质组的变化。结果表明，蛋白水解、细胞保护机制和细胞浸润的迹象很早就出现了。在 HS 1 天后，似乎溶酶体激活的信号而不是程序性细胞死亡（细胞凋亡）触发了整个骨骼肌的蛋白水解。此外，泛素-蛋白酶体途径在后期仍保持升高，而当萎缩完全建立时，所有其他蛋白水解参数都恢复到对照值。通过蛋白质组学，为向糖酵解的代谢改变以及细胞骨架重塑提供了证据，这表明产生力的能力降低。总的来说，我们的数据强调了蛋白水解的早期和协调的时相依赖性激活，这解释了萎缩条件下腓肠肌中观察到的全蛋白质组改变。
