title: Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction.
abstract: High intensity training induces muscle damage in dystrophin-deficient mdx mice, an animal model for Duchenne muscular dystrophy. However, low intensity training (LIT) rescues the mdx phenotype and even reduces the level of protein carbonylation, a marker of oxidative damage. Until now, beneficial effects of LIT were mainly assessed at the physiological level. We investigated the effects of LIT at the molecular level on 8-week-old wild-type and mdx muscle using 2D Western blot and protein-protein interaction analysis. We found that the fast isoforms of troponin T and myosin binding protein C as well as glycogen phosphorylase were overcarbonylated and downregulated in mdx muscle. Some of the mitochondrial enzymes of the citric acid cycle were overcarbonylated, whereas some proteins of the respiratory chain were downregulated. Of functional importance, ATP synthase was only partially assembled, as revealed by Blue Native PAGE analysis. LIT decreased the carbonylation level and increased the expression of fast isoforms of troponin T and of myosin binding protein C, and glycogen phosphorylase. In addition, it increased the expression of aconitate hydratase and NADH dehydrogenase, and fully restored the ATP synthase complex. Our study demonstrates that the benefits of LIT are associated with lowered oxidative damage as revealed by carbonylation and higher expression of proteins involved in energy metabolism and muscle contraction. Potentially, these results will help to design therapies for DMD based on exercise mimicking drugs.
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors: Janek
authors: J
authors: Hyzewicz
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors: Jun
authors: J
authors: Tanihata
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors: Mutsuki
authors: M
authors: Kuraoka
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors: Naoki
authors: N
authors: Ito
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors: Yuko
authors: Y
authors: Miyagoe-Suzuki
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: takeda@ncnp.go.jp.
authors: Shin'ichi
authors: S
authors: Takeda
mesh_terms: D000154:Aconitate Hydratase / Q000096:biosynthesis; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002952:Citric Acid Cycle / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation; D016189:Dystrophin / Q000235:genetics; D004734:Energy Metabolism / Q000502:physiology*; D024981:Glycogen Phosphorylase / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne; D009245:NADH Dehydrogenase / Q000096:biosynthesis; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal / Q000379:methods*; D050050:Protein Carbonylation / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics; D020107:Troponin T / Q000096:biosynthesis / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D000154:Aconitate Hydratase; D002352:Carrier Proteins; D016189:Dystrophin; D024981:Glycogen Phosphorylase; D025261:Mitochondrial Proton-Translocating ATPases; D009245:NADH Dehydrogenase; D020033:Protein Isoforms; D020107:Troponin T; D000099163:Myosin Binding Protein C
keywords: Blue Native PAGE; Exercise; Oxidative stress; Proteomic; Skeletal muscle; mdx mouse