Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
J Proteomics. 2018 Jan 6;170:43-58. doi: 10.1016/j.jprot.2017.09.009. Epub 2017 Sep 28.
Weakness and fatigability are typical features of Duchenne muscular dystrophy patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise. In the present study, we describe, the pattern of differentially abundant spots that is associated to the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different abundance between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories. Interestingly exercise induced an increase of typical fast twitch fiber proteins (Troponin T fast skeletal muscle, Troponin I fast skeletal muscle and Myozenin-1) combined with an increase of several glycolytic enzymes. Concerning energy transfer, Adenylate kinase, showed a marked decrease when compared with non-exercised mdx. The decline of this enzyme correlates with increased Creatin kinase enzyme, suggesting that a compensatory energy metabolism mechanism could be activated in mdx mouse skeletal muscle following exercise. In addition, we analysed muscles from exercised mdx mice treated with two natural anti-oxidant compounds, apocynin and taurine, that in our previous study, were proved to be beneficial on some pathology related parameters, and we showed that these compounds can counteract exercise-induced changes in the abundance of several proteins.
Mdx mouse model of Duchenne muscular dystrophy shows a phenotype of the disorder milder than in human sufferers. This phenotype can be worsened by a different protocols of chronic exercise. These protocols can mimic the muscle progressive damage observed in humans, can allow studying the effects of inadequate training on dystrophic muscles and have been largely used to assess the ability of a drug to reduce the damage induced by exercise. In this study, we describe for the first time, the pattern of protein variation associated with the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different amount between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories and their variation indicates that mdx exercised muscle are not able to carry out the metabolic changes associated to fast-to-slow transition typically observed in aerobically trained muscle.
虚弱和疲劳是杜氏肌营养不良症患者的典型特征，在慢性跑步机运动的情况下，mdx 营养不良症小鼠的病情会加重。在本研究中，我们描述了与慢性运动引起的肌营养不良表型恶化相关的差异丰度斑点模式。我们的蛋白质组学分析指出，在久坐不动的 mdx 小鼠和运动的 mdx 小鼠之间，有 34 个蛋白质斑点的丰度不同。这些蛋白质主要属于葡萄糖代谢、能量产生和肌节结构类别。有趣的是，运动诱导了典型的快肌纤维蛋白（快骨骼肌肌钙蛋白 T、快骨骼肌肌钙蛋白 I 和肌联蛋白-1）的增加，同时几种糖酵解酶的增加。关于能量转移，与非运动的 mdx 相比，腺嘌呤激酶表现出明显的下降。这种酶的下降与肌酸激酶酶的增加相关，表明在运动后 mdx 小鼠骨骼肌中可能激活了一种补偿性的能量代谢机制。此外，我们分析了运动后的 mdx 小鼠肌肉，这些肌肉用两种天然抗氧化化合物（apocynin 和牛磺酸）处理，在我们之前的研究中，这两种化合物被证明对一些与病理相关的参数有益，我们表明这些化合物可以抵消运动引起的几种蛋白质丰度变化。
杜氏肌营养不良症的 mdx 小鼠模型的表型比人类患者的表型更轻。这种表型可以通过不同的慢性运动方案来加重。这些方案可以模拟人类中观察到的肌肉进行性损伤，可以研究不适当训练对肌营养不良肌肉的影响，并已被广泛用于评估药物减轻运动引起的损伤的能力。在这项研究中，我们首次描述了与慢性运动引起的肌营养不良表型恶化相关的蛋白质变化模式。我们的蛋白质组学分析指出，在久坐不动的 mdx 小鼠和运动的 mdx 小鼠之间，有 34 个蛋白质斑点的丰度不同。这些蛋白质主要属于葡萄糖代谢、能量产生和肌节结构类别，它们的变化表明，运动后的 mdx 肌肉不能进行与有氧训练肌肉中典型的快肌向慢肌转变相关的代谢变化。
