Department of General and Environmental Physiology and Centre of Excellence in Comparative Genomics (CEGBA), University of Bari, 70126, Bari, Italy.
Eur J Appl Physiol. 2010 Dec;110(6):1215-24. doi: 10.1007/s00421-010-1592-6. Epub 2010 Aug 24.
Muscle atrophy occurring in several pathophysiological conditions determines decreases in muscle protein synthesis, increases in the rate of proteolysis and changes in muscle fiber composition. To determine the effect of muscle atrophy induced by hindlimb unloading (HU) on membrane proteins from rat soleus, a proteomic approach based on two-dimensional Blue Native/SDS-PAGE was performed. Proteomic analysis of normal and HU soleus muscle demonstrates statistically significant changes in the relative level of 36 proteins. Among the proteins identified by mass spectrometry, most are involved in pathways associated with muscle fuel utilization, indicating a shift in metabolism from oxidative to glycolytic. Moreover, immunoblotting analysis revealed an increase in aquaporin-4 (AQP4) water channel and an alteration of proteins belonging to the dystrophin-glycoprotein complex (DGC). AQP4 and DGC are regulated in soleus muscle subjected to simulated microgravity in response to compensatory mechanisms induced by muscle atrophy, and they parallel the slow-to-fast twitch conversion that occurs in soleus fibers during HU. In conclusion, the alterations of soleus muscle membrane proteome may play a pivotal role in the mechanisms involved in disuse-induced muscle atrophy.
在几种病理生理条件下发生的肌肉萎缩会导致肌肉蛋白质合成减少、蛋白水解率增加以及肌肉纤维组成的变化。为了确定由后肢去负荷（HU）引起的肌肉萎缩对大鼠比目鱼肌膜蛋白的影响，采用基于二维 Blue Native/SDS-PAGE 的蛋白质组学方法进行了研究。正常和 HU 比目鱼肌的蛋白质组学分析表明，36 种蛋白质的相对水平有统计学意义的变化。通过质谱鉴定的蛋白质中，大多数与肌肉燃料利用途径相关，表明代谢从氧化向糖酵解转变。此外，免疫印迹分析显示水通道蛋白-4（AQP4）和属于营养不良蛋白聚糖复合物（DGC）的蛋白质发生改变。AQP4 和 DGC 在模拟微重力条件下的比目鱼肌中受到调节，以响应由肌肉萎缩引起的代偿机制，并且与 HU 过程中比目鱼肌纤维中发生的慢肌向快肌转化平行。总之，比目鱼肌膜蛋白质组的改变可能在废用性肌肉萎缩相关机制中起关键作用。
