Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction
Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction
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DOI：
10.1016/j.freeradbiomed.2015.01.023
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发表时间：
2015-05-01
影响因子：
7.4
通讯作者：
Takeda, Shin'ichi
中科院分区：
文献类型：
--
作者：
Hyzewicz, Janek;Tanihata, Jun;Takeda, Shin'ichi
高强度训练诱导肌营养不良蛋白缺陷mdx小鼠（杜氏肌营养不良动物模型）的肌肉损伤。然而，低强度训练（LIT）挽救了mdx表型，甚至降低了蛋白质羰基化水平，这是氧化损伤的标志。到目前为止，LIT的有益作用主要是在生理水平上进行评估。我们通过二维Western blot和蛋白-蛋白相互作用分析，在分子水平上研究了LIT对8周龄野生型和mdx肌肉的影响。我们发现肌钙蛋白T和肌球蛋白结合蛋白C的快速亚型以及糖原磷酸化酶在mdx肌肉中过度羰基化和下调。柠檬酸循环的一些线粒体酶过度羰基化，而呼吸链的一些蛋白质下调。Blue Native PAGE分析显示，ATP合酶仅部分组装，具有重要的功能。LIT降低了羰基化水平，增加了肌钙蛋白T、肌球蛋白结合蛋白C和糖原磷酸化酶的快速异构体的表达。此外，它还增加了乌头酸水合酶和NADH脱氢酶的表达，并充分恢复了ATP合酶复合物。我们的研究表明，通过羰基化和参与能量代谢和肌肉收缩的蛋白质的高表达，LIT的益处与降低氧化损伤有关。潜在地，这些结果将有助于设计基于运动模拟药物的DMD治疗方法。(C) 2015年作者。Elsevier Inc.出版。
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. (C) 2015 The Authors. Published by Elsevier Inc.