Does oxidative stress modulate limb muscle atrophy in severe COPD patients?
Does oxidative stress modulate limb muscle atrophy in severe COPD patients?
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DOI：
10.1183/09031936.00137211
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发表时间：
2012-10-01
影响因子：
24.3
通讯作者：
Barreiro, Esther
中科院分区：
文献类型：
--
作者：
Fermoselle, Clara;Rabinovich, Roberto;Barreiro, Esther
氧化应激可能对表现出不同身体成分的严重慢性阻塞性肺疾病（COPD）患者外周肌肉蛋白质损失有不同的调节作用。在伴有和不伴有肌肉萎缩的严重COPD患者以及久坐对照中，对其肢体肌肉中蛋白质、肌球蛋白重链（MyHC）和肌核、超氧阴离子、抗氧化剂、肌动蛋白、肌酸激酶、碳酸酐酶-3、泛素-蛋白酶体系统、氧化还原信号通路、炎症和肌肉结构以及损伤的氧化水平进行了量化。与对照组相比，在肌肉萎缩的COPD患者的股四头肌中，蛋白质羰基化、MyHC和肌核氧化、超氧阴离子产生、超氧化物歧化酶、总蛋白泛素化、E2（14k）、atrogenin -1、FoxO1和p65水平较高，而MyHC、肌酸激酶、碳酸酐酶-3、肌原素含量和快肌纤维大小均降低。重要的是，在非浪费性COPD患者中，MyHC比对照组更氧化，其含量得以保存。肌肉炎症和谷胱甘肽水平在患者和对照组之间没有差异。在所有患者中，肌肉结构异常增加，肌肉力量和运动能力下降。在严重慢性阻塞性肺病中，尽管肌肉氧化应激与身体成分无关，但蛋白质泛素化和MyHC损失仅在肌肉萎缩的患者中增强。氧化应激似乎不能直接调节这些患者的肌肉蛋白损失。
Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition.Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin-proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls.Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2(14k), atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced.In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.