Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Brazil; Glycoproteomics Laboratory, Department of Parasitology, University of Sao Paulo, Sao Paulo, Brazil; Brazilian Navy, Directorate of Weapons Systems of the Navy, Department of Chemistry, Rio de Janeiro, Brazil; Centro de Educação Física Almirante Adalberto Nunes, Brazilian Navy, Rio de Janeiro 21941-901, Brazil.
Glycoproteomics Laboratory, Department of Parasitology, University of Sao Paulo, Sao Paulo, Brazil.
J Proteomics. 2022 Apr 30;258:104498. doi: 10.1016/j.jprot.2022.104498. Epub 2022 Feb 5.
Exertional rhabdomyolysis (ERM), a condition often associated with strenuous exercise, a common practice in the military activities, can be defined as the process of injury and rupture of muscle cell membranes, with leakage of its components into the bloodstream. Creatine kinase (CK) has been used for ERM diagnosis, albeit several studies reported the discrepancy between CK levels and clinical signs or symptoms. In this study, we analyzed the biochemical profile of the blood, and the urinary proteome of ten marine soldiers in a special training course. The samples were collected in two periods, M1 and M2, which correspond to the lowest and highest CK levels during training, respectively. Quantitative urinary proteome profile of M1 and M2 showed changes in proteins involved in immune system and cell adhesion-related pathways after strenuous physical exercise. Changes in the abundance of several proteins was observed in individuals carrying genetic polymorphisms related to greater risk for muscle damage. A panel of proteins (CTSH, PIK3IP1, DEFB1, ITGB1, BCAN, and TNFRSF10C) presented high correlation with classical blood biochemical markers of ERM and AGT MET235Thr and ACE I/D polymorphisms. These proteins represent potential urine markers of muscle damage due to intense physical conditions such as military training activities. SIGNIFICANCE: This study analyzed the blood and urine of a cohort of marine soldiers enrolled in a special training program including missions with low and high exposure to strenuous exercise. The biochemical blood profile, polymorphisms mapping and mass spectrometry-based analyses of the urinary proteome was evaluated in such a controlled samples. A total of 226 urinary proteins associated to immune system, cell adhesion and redox homeostasis were significantly changes during ERM shedding lights on the disease pathogenesis. In particular, a panel of six proteins were associated to classical ERM markers and could be used as early non invasive biomarkers.
运动性横纹肌溶解症（ERM）是一种常与剧烈运动相关的疾病，在军事活动中较为常见，其特征为肌肉细胞膜损伤和破裂，导致其成分渗漏到血液中。肌酸激酶（CK）已被用于 ERM 的诊断，但有几项研究报告称 CK 水平与临床症状或体征之间存在差异。在这项研究中，我们分析了十位海军陆战队员在特殊训练课程中的血液生化特征和尿液蛋白质组。这些样本分别在 M1 和 M2 两个时期采集，分别对应于训练期间 CK 水平最低和最高的时期。M1 和 M2 的定量尿液蛋白质组谱显示，剧烈运动后与免疫系统和细胞黏附相关途径相关的蛋白质发生了变化。在与肌肉损伤风险增加相关的遗传多态性个体中，观察到几种蛋白质丰度的变化。一组蛋白质（CTSH、PIK3IP1、DEFB1、ITGB1、BCAN 和 TNFRSF10C）与 ERM 的经典血液生化标志物以及 AGT MET235Thr 和 ACE I/D 多态性呈高度相关。这些蛋白质代表了由于剧烈运动等军事训练活动引起的肌肉损伤的潜在尿液标志物。意义：本研究分析了一组参加包括低强度和高强度暴露于剧烈运动的特殊训练计划的海军陆战队员的血液和尿液。对血液生化特征、多态性图谱以及基于质谱的尿液蛋白质组学分析进行了评估。在 ERM 期间，与免疫系统、细胞黏附和氧化还原稳态相关的 226 种尿液蛋白质发生了显著变化，揭示了疾病的发病机制。特别是，一组六种蛋白质与经典的 ERM 标志物相关，可作为早期非侵入性生物标志物。
