Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery.
Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery.
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DOI：
10.1113/expphysiol.2009.049650
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发表时间：
2010-01
影响因子：
2.7
通讯作者：
Powers SK
中科院分区：
文献类型：
--
作者：
McClung JM;Deruisseau KC;Whidden MA;Van Remmen H;Richardson A;Song W;Vrabas IS;Powers SK
低水平的活性氧（ROS）产生对于优化非疲劳肌肉中的肌肉力量产生是必要的。相反，持续高水平的ROS产生与肌肉力量产生受损和收缩诱导的骨骼肌疲劳有关。使用基因工程小鼠，我们测试的假设，独立的转基因过氧化氢酶（CAT），铜/锌超氧化物歧化酶（CuZnSOD; SOD 1）或锰超氧化物歧化酶（MnSOD; SOD 2）抗氧化酶的过度表达将产生负面影响力生产在非疲劳的膈肌，但会延迟肌肉疲劳的发展，并提高疲劳收缩后的力量恢复。对来自野生型同窝小鼠（WT）和来自CAT、SOD 1和SOD 2过表达小鼠的膈肌进行体外收缩方案以研究力-频率特性、疲劳特性和从疲劳恢复的时间过程。CAT、SOD 1和SOD 2过表达子在20-300 Hz的刺激频率下产生的比力（单位为N cm-2）较WT同窝仔小，并且产生的最大强直力也较WT同窝仔小。肌肉疲劳和疲劳恢复的相对发展不受任何抗氧化酶的转基因过表达的影响。在形态学上，CAT和SOD 2转基因动物中表达IIA型肌球蛋白重链的膈肌肌纤维的平均横截面积（μm2）减少，所有转基因小鼠的膈肌中非收缩组织的百分比增加。总之，我们的研究结果不支持独立的抗氧化酶的过度表达保护膈肌收缩引起的疲劳或改善疲劳恢复的假设。此外，我们的数据是一致的概念，ROS的基础水平是重要的，以优化肌肉力量的生产，因为转基因过表达的主要细胞抗氧化剂与收缩功能障碍。最后，独立的内源性抗氧化剂的转基因过表达改变了膈肌骨骼肌的形态，这些变化也可能有助于减少在这些动物中观察到的比力生产。
Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with contractile dysfunction. Finally, the transgenic overexpression of independent endogenous antioxidants alters diaphragm skeletal muscle morphology, and these changes may also contribute to the diminished specific force production observed in these animals.
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影响因子：
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