Plaza-Florido Abel, Santos-Lozano Alejandro, López-Ortiz Susana, Gálvez Beatriz G, Arenas Joaquín, Martín Miguel A, Valenzuela Pedro L, Pinós Tomàs, Lucia Alejandro, Fiuza-Luces Carmen
Pediatric Exercise and Genomics Research Center, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, California, USA.
i+HeALTH, European University Miguel de Cervantes, Valladolid, Spain.
Exp Physiol. 2025 Feb;110(2):293-306. doi: 10.1113/EP092308. Epub 2024 Nov 21.
We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (n = 10) and wild-type (n = 8) mice, as models of intrinsically 'low' and 'normal' AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromatography with tandem mass spectrometry, with the Search Tool for the Retrieval of Interacting Genes/Proteins database used to generate protein-protein interaction (PPI) networks and enrichment analyses. AC was significantly associated (P-values ranging from 0.0002 to 0.049) with 73 (McArdle) and 61 (wild-type) proteins (r-values from -0.90 to 0.94). These proteins were connected in PPI networks that enriched biological processes involved in skeletal muscle structure/function in both groups (false discovery rate <0.05). In McArdle mice, the proteins associated with AC were involved in skeletal muscle fibre differentiation/development, lipid oxidation, mitochondrial function and calcium homeostasis, whereas in wild-type animals AC-associated proteins were related to cytoskeleton structure (intermediate filaments), cell cycle regulation and endocytic trafficking. Two proteins (WEE2, THYG) were associated with AC (negatively and positively, respectively) in both groups. Only 14 of the 132 proteins (∼11%) associated with AC in McArdle or wild-type mice were also associated with those previously reported to be modified by aerobic training in these mice, providing preliminary evidence for a large divergence in the muscle proteome signature linked to aerobic training or AC, irrespective of AC (intrinsically low or normal) levels. Our findings might help to gain insight into the molecular mechanisms underlying AC at the muscle tissue level.
我们分别以本质上“低”和“正常”有氧能力（AC）的模型，即麦克阿德尔小鼠（n = 10）和野生型小鼠（n = 8），探究了有氧能力（AC）与骨骼肌蛋白质组之间的关联。AC通过跑步机跑步直至力竭所达到的总距离来确定。使用液相色谱串联质谱法研究股四头肌蛋白质组，并使用用于检索相互作用基因/蛋白质的搜索工具数据库生成蛋白质-蛋白质相互作用（PPI）网络和富集分析。AC与73种（麦克阿德尔小鼠）和61种（野生型小鼠）蛋白质显著相关（P值范围为0.0002至0.049）（r值范围为-0.90至0.94）。这些蛋白质在PPI网络中相互连接，富集了两组中与骨骼肌结构/功能相关的生物学过程（错误发现率<0.05）。在麦克阿德尔小鼠中，与AC相关的蛋白质参与骨骼肌纤维分化/发育、脂质氧化、线粒体功能和钙稳态，而在野生型动物中，与AC相关的蛋白质与细胞骨架结构（中间丝）、细胞周期调控和内吞运输有关。两种蛋白质（WEE2、THYG）在两组中均与AC相关（分别为负相关和正相关）。在麦克阿德尔或野生型小鼠中与AC相关的132种蛋白质中，只有14种（约11%）也与先前报道的在这些小鼠中经有氧训练而发生改变的蛋白质相关，这为与有氧训练或AC相关的肌肉蛋白质组特征存在很大差异提供了初步证据，无论AC（本质上低或正常）水平如何。我们的发现可能有助于深入了解肌肉组织水平上AC的分子机制。
