Reduction in <i>mdx</i> mouse muscle degeneration by low-intensity endurance exercise: a proteomic analysis in quadriceps muscle of exercised compared with sedentary <i>mdx</i> mice

Fontana, Simona; Schillaci, Odessa; Frinchi, Monica; Giallombardo, Marco; Morici, Giuseppe; Liberto, Valentina Di; Alessandro, Riccardo; Leo, Giacomo De; Perciavalle, Vincenzo; Belluardo, Natale; Mudò, Giuseppa

doi:10.1042/bsr20150013

Cited by 20 publications

(24 citation statements)

References 38 publications

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“…They described reduction of necrotic and inflammatory infiltrate areas (Frinchi et al, 2014), modulation of antioxidant enzymes (Fontana et al, 2015) and reduction of skeletal dystrophic muscle inflammatory process of mdx model (Hyzewicz et al, 2017). The results of these researches reinforces that modalities of non-voluntary training and of low intensity can bring beneficial responses of the dystrophic muscle of the mdx model even though few of them have investigated morphological parameters of the dystrophic muscle.…”

Section: Discussionmentioning

confidence: 75%

“…Fibrosis is a final result of a chronic inflammatory process on dystrophic muscle due to the absence of dystrophin (Smith & Barton;Fontana et al, 2015). We have shown that this modality and intensity of training affected the intramuscular fibrosis in a beneficial way but further investigations are required to explain if LIT has delayed the formation of an intramuscular fibrosis or if it was reorganized by the contraction-induced adaptations on skeletal muscle tissue.…”

Section: Discussionmentioning

confidence: 99%

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Low Intensity Training Provokes Adaptations on Muscle Fibrosis of a Muscular Dystrophy Model

et al. 2018

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SUMMARY:Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder with progressive clinical signs until death, around the second decade of life. Mdx is the most used animal model to pre-clinical studies of DMD. Parameters of exercise on this muscular disease are still unknown. This research aimed to investigate if the low intensity treadmill training would exacerbate the markers of muscle injury, fibrosis, and the composition of the extracellular matrix by type I and III collagens of the mdx model. Dystrophic 11-week-old male mice were separated in exercised (mdxE, n=8) and sedentary (mdxC, n=8) groups. Wild-type mice were used as control (WT, n=8). Exercised group underwent a LIT protocol (9 m/min, 30min, 3days/week, 60 days) on a horizontal treadmill. Gastrocnemius muscle was collected at day 60 and processed to morphological and morphometric analyzes. Sedentary mdx animals presented inflammatory infiltrate and necrotic fibers. Histochemical analysis revealed that the perimysium of the mdxC group is organized into thick and clustered collagen fibers, which generates a larger area of intramuscular collagen fibers for these animals. Histomorphometry attested that fraction area of collagen fibers of mdxC group was higher than mdxE group (p=0.04) and mdxE group values similar to WT group (p=1.00). Centrally located nuclei fibers and the variance coefficient (VC) of minimal Feret's diameter was similar in mdxE and mdxC groups (p=1.00) and both groups presented higher mean values than WT group (p<0.00). Immunohistochemistry revealed the presence of type I collagen mainly in the mdxC group. LIT protocol had not exacerbated muscle injuries resulting from the dystrophindeficiency membrane fragility at the same time that had reduced the intramuscular collagen deposition. LIT had positively influenced these markers of dystrophic muscle injury on gastrocnemius muscle of mdx model.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Low Intensity Training Provokes Adaptations on Muscle Fibrosis of a Muscular Dystrophy Model

et al. 2018

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“…We recently reported that inflammatory‐necrotic areas in gastrocnemius and quadriceps muscles of mdx mice significantly decreased following low‐intensity endurance exercise training for 6 weeks (Frinchi et al, ). Significant recovery of damaged skeletal muscle occurred (Belluardo et al, ; Frinchi et al, ), and reduced cell degeneration in mdx muscles was associated with modulation of proteins involved in oxidative stress defense (Fontana et al, ). The majority of studies on the effects of low‐intensity or voluntary exercise reported protective effects of training on skeletal muscles of mdx mice (Hayes and Williams, ; Call et al, ; Baltgalvis et al, ; Frinchi et al, ; Gordon et al, ) (Table ).…”

Section: Summary Of Studies On the Effects Of Training On Limb Musclementioning

confidence: 99%

Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice

Morici

Frinchi

Pitruzzella

et al. 2017

Journal Cellular Physiology

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In the mdx mice model of Duchenne Muscular Dystrophy (DMD), mild endurance exercise training positively affected limb skeletal muscles, whereas few and controversial data exist on the effects of training on the diaphragm. The diaphragm was examined in mdx (C57BL/10ScSn-Dmdmdx) and wild-type (WT, C57BL/10ScSc) mice under sedentary conditions (mdx-SD, WT-SD) and during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days (training: 5 d/wk for 6 weeks), diaphragm muscle morphology and Cx39 protein were assessed. In addition, tissue levels of the chaperonins Hsp60 and Hsp70 and the p65 subunit of nuclear factor-kB (NF-kB) were measured in diaphragm, gastrocnemius, and quadriceps in each experimental group at all time points. Although morphological analysis showed unchanged total area of necrosis/regeneration in the diaphragm after training, there was a trend for larger areas of regeneration than necrosis in the diaphragm of mdx-EX compared to mdx-SD mice. However, the levels of Cx39, a protein associated with active regeneration in damaged muscle, were similar in the diaphragm of mdx-EX and mdx-SD mice. Hsp60 significantly decreased at 45 days in the diaphragm, but not in limb muscles, in both trained and sedentary mdx compared to WT mice. In limb muscles, but not in the diaphragm, Hsp70 and NF-kB p65 levels were increased in mdx mice irrespective of training at 30 and 45 days. Therefore, the diaphragm of mdx mice showed little inflammatory and stress responses over time, and appeared hardly affected by mild endurance training. J. Cell. Physiol. 232: 2044-2052, 2017. © 2016 Wiley Periodicals, Inc.

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“…Therefore, proteome profiling of exercised muscle in pathophysiological conditions may help to disclose how exercise training modulates muscle wasting. This field of research is just beginning and, the few existing data on this topic was obtained from the study of pathophysiological conditions such as Duchene muscular dystrophy (DMD) , type 2 diabetes mellitus (T2DM) , insulin resistance , aging and bed rest .…”

Section: Exploring the Cross‐talk Between Exercise And Wasting Diseasesmentioning

confidence: 99%

“…The majority of data on this topic was gathered with gel‐based techniques, though LC‐MS/MS has been recently used to complement gel‐based methods and increase proteomic data . The few studies performed on proteome plasticity of skeletal muscle in response to exercise involved animal models and humans , and were designed to assess the effects of different modes of exercise such as swimming, running, cycling or vibration, exercise of different intensities and duration. Table summarizes the studies focused on the impact of exercise in skeletal muscle proteome.…”

Section: Introductionmentioning

confidence: 99%

Uncovering the exercise‐related proteome signature in skeletal muscle

et al. 2016

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Exercise training has been recommended as a nonpharmacological strategy for the prevention and attenuation of skeletal muscle atrophy in distinct pathophysiological conditions. Despite the well-established phenotypic alterations, the molecular mechanisms underlying exercise-induced skeletal muscle remodeling are poorly characterized. Proteomics based on mass spectrometry have been successfully applied for the characterization of skeletal muscle proteome, representing a pivotal approach for the wide characterization of the molecular networks that lead to skeletal muscle remodeling. Nevertheless, few studies were performed to characterize the exercise-induced proteome remodeling of skeletal muscle, with only six research papers focused on the cross-talk between exercise and pathophysiological conditions. In order to add new insights on the impact of distinct exercise programs on skeletal muscle proteome, molecular network analysis was performed with bioinformatics tools. This analysis highlighted an exercise-related proteome signature characterized by the up-regulation of the capacity for ATP generation, oxygen delivery, antioxidant capacity and regulation of mitochondrial protein synthesis. Chronic endurance training up-regulates the tricarboxylic acid cycle and oxidative phosphorylation system, whereas the release of calcium ion into cytosol and amino acid metabolism are the biological processes up-regulated by a single bout of exercise. Other issues as exercise intensity, load, mode and regimen as well as muscle type also influence the exercise-induced proteome signature. The comprehensive analysis of the molecular networks modulated by exercise training in health and disease, taking in consideration all these variables, might not only support the therapeutic effect of exercise but also highlight novel targets for the development of enhanced pharmacological strategies.

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Reduction in mdx mouse muscle degeneration by low-intensity endurance exercise: a proteomic analysis in quadriceps muscle of exercised compared with sedentary mdx mice

Cited by 20 publications

References 38 publications

Low Intensity Training Provokes Adaptations on Muscle Fibrosis of a Muscular Dystrophy Model

Low Intensity Training Provokes Adaptations on Muscle Fibrosis of a Muscular Dystrophy Model

Mild Aerobic Exercise Training Hardly Affects the Diaphragm of mdx Mice

Uncovering the exercise‐related proteome signature in skeletal muscle

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