Mechanistic Role of Reactive Oxygen Species and Therapeutic Potential of Antioxidants in Denervation- or Fasting-Induced Skeletal Muscle Atrophy.
Mechanistic Role of Reactive Oxygen Species and Therapeutic Potential of Antioxidants in Denervation- or Fasting-Induced Skeletal Muscle Atrophy.
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活性氧的机制作用和抗氧化剂在去神经或禁食引起的骨骼肌萎缩中的治疗潜力
DOI：
10.3389/fphys.2018.00215
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发表时间：
2018
影响因子：
4
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Qiu J;Fang Q;Xu T;Wu C;Xu L;Wang L;Yang X;Yu S;Zhang Q;Ding F;Sun H
骨骼肌萎缩发生在各种条件下，如废用、去神经支配、禁食、衰老和各种疾病。尽管其潜在的分子机制尚未完全清楚，但骨骼肌萎缩与活性氧（ROS）的过度产生密切相关。本研究旨在从基因调控的角度探讨ROS在骨骼肌萎缩中的作用，并进一步探讨抗氧化剂对骨骼肌萎缩的治疗作用。微阵列数据显示，在失神经支配（坐骨神经损伤）萎缩的小鼠比目鱼肌中，许多ROS产生的正调控因子基因表达上调，许多ROS产生的负调控因子基因表达下调。去神经小鼠比目鱼肌或禁食（营养剥夺）的禁食C2 C12肌管中的活性氧水平显着增加。然后分别用N-乙酰基-L-半胱氨酸（NAC，一种临床使用的抗氧化剂）或吡咯喹啉醌（PQQ，一种天然存在的抗氧化剂）处理这两种肌肉样品。NAC和PQQ治疗组与对照组相比，（1）逆转了两个肌肉样品中ROS水平的升高，（2）减轻了失神经支配小鼠肌肉横截面积（CSA）或禁食C2 C12肌管直径的减小;（3）增加肌球蛋白重链（MHC）水平，降低肌萎缩F盒（MAFbx）和肌肉特异性环指蛋白-1（MuRF-1）水平。总的来说，这些结果表明，增加的ROS水平是，至少部分地，负责去神经或禁食诱导的骨骼肌萎缩，抗氧化剂可能通过ROS相关机制抵抗萎缩作用。
Skeletal muscle atrophy occurs under various conditions, such as disuse, denervation, fasting, aging, and various diseases. Although the underlying molecular mechanisms are still not fully understood, skeletal muscle atrophy is closely associated with reactive oxygen species (ROS) overproduction. In this study, we aimed to investigate the involvement of ROS in skeletal muscle atrophy from the perspective of gene regulation, and further examine therapeutic effects of antioxidants on skeletal muscle atrophy. Microarray data showed that the gene expression of many positive regulators for ROS production were up-regulated and the gene expression of many negative regulators for ROS production were down-regulated in mouse soleus muscle atrophied by denervation (sciatic nerve injury). The ROS level was significantly increased in denervated mouse soleus muscle or fasted C2C12 myotubes that had suffered from fasting (nutrient deprivation). These two muscle samples were then treated with N-acetyl-L-cysteine (NAC, a clinically used antioxidant) or pyrroloquinoline quinone (PQQ, a naturally occurring antioxidant), respectively. As compared to non-treatment, both NAC and PQQ treatment (1) reversed the increase in the ROS level in two muscle samples; (2) attenuated the reduction in the cross-sectional area (CSA) of denervated mouse muscle or in the diameter of fasted C2C12 myotube; (3) increased the myosin heavy chain (MHC) level and decreased the muscle atrophy F-box (MAFbx) and muscle-specific RING finger-1 (MuRF-1) levels in two muscle samples. Collectively, these results suggested that an increased ROS level was, at least partly, responsible for denervation- or fasting-induced skeletal muscle atrophy, and antioxidants might resist the atrophic effect via ROS-related mechanisms.
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影响因子：
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作者：
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DOI：
10.1016/j.biocel.2014.04.024
发表时间：
2014-08-01
影响因子：
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作者：
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通讯作者：
Torrisi, Maria Rosaria