Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, PR China; Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Ministry of Education, Xi'an 710069, PR China.
Laboratory for Bone Metabolism, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, PR China.
Comp Biochem Physiol Part D Genomics Proteomics. 2018 Jun;26:20-31. doi: 10.1016/j.cbd.2018.02.002. Epub 2018 Feb 13.
Previous hibernation studies demonstrated that such a natural model of skeletal muscle disuse causes limited muscle atrophy and a significant fast-to-slow fiber type shift. However, the underlying mechanism as defined in a large-scale analysis remains unclarified. Isobaric tags for relative and absolute quantification (iTRAQ) based quantitative analysis were used to examine proteomic changes in the fast extensor digitorum longus muscles (EDL) of Daurian ground squirrels (Spermophilus dauricus). Although the wet weights and fiber cross-sectional area of the EDL muscle showed no significant decrease, the percentage of slow type fiber was 61% greater (P < 0.01) in the hibernation group. Proteomics analysis identified 264 proteins that were significantly changed (ratio < 0.83 or >1.2-fold and P < 0.05) in the hibernation group, of which 23 proteins were categorized into energy production and conversion and translation and 22 proteins were categorized into ribosomal structure and biogenesis. Along with the validation by western blot, MAPKAP kinase 2, ATP5D, ACADSB, calcineurin, CSTB and EIF2S were up-regulated in the hibernation group, whereas PDK4, COX II and EIF3C were down-regulated in the hibernation group. MAPKAP kinase 2 and PDK4 were associated with glycolysis, COX II and ATP5D were associated with oxidative phosphorylation, ACADSB was associated with fatty acid metabolism, calcineurin and CSTB were associated with catabolism, and EIF2S and EIF3C were associated with anabolism. Moreover, the total proteolysis rate of EDL in the hibernation group was significantly inhibited compared with that in the pre-hibernation group. These distinct energy and protein metabolism characteristics may be involved in myofiber type conversion and resistance to atrophy in the EDL of hibernating Daurian ground squirrels.
先前的冬眠研究表明，这种自然的骨骼肌废用模型会导致有限的肌肉萎缩和显著的快肌向慢肌纤维类型转变。然而，在大规模分析中定义的潜在机制仍不清楚。采用相对和绝对定量同位素标记（iTRAQ）基于定量分析的方法，研究了达乌尔黄鼠（Spermophilus dauricus）快速伸趾长肌（EDL）中的蛋白质组变化。尽管 EDL 肌肉的湿重和纤维横截面积没有显著下降，但冬眠组的慢型纤维百分比增加了 61%（P<0.01）。蛋白质组学分析鉴定出 264 种蛋白质在冬眠组中发生了显著变化（比值<0.83 或>1.2 倍，P<0.05），其中 23 种蛋白质分为能量产生和转化以及翻译，22 种蛋白质分为核糖体结构和生物发生。通过 Western blot 验证，MAPKAP kinase 2、ATP5D、ACADSB、钙调神经磷酸酶、CSTB 和 EIF2S 在冬眠组中上调，而 PDK4、COX II 和 EIF3C 在冬眠组中下调。MAPKAP kinase 2 和 PDK4 与糖酵解有关，COX II 和 ATP5D 与氧化磷酸化有关，ACADSB 与脂肪酸代谢有关，钙调神经磷酸酶和 CSTB 与分解代谢有关，EIF2S 和 EIF3C 与合成代谢有关。此外，与预冬眠组相比，冬眠组 EDL 的总蛋白水解率显著受到抑制。这些不同的能量和蛋白质代谢特征可能参与了达乌尔黄鼠冬眠 EDL 肌纤维类型的转换和抗萎缩。
