Proteome analysis in dystrophic mdx mouse muscle reveals a drastic alteration of key metabolic and contractile proteins after chronic exercise and the potential modulation by anti-oxidant compounds

Abstract

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. SignificanceMdx 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.