Response to Electrostimulation Is Impaired in Muscle Cells from Patients with Chronic Obstructive Pulmonary Disease.

Response to Electrostimulation Is Impaired in Muscle Cells from Patients with Chronic Obstructive Pulmonary Disease.
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DOI:
10.3390/cells10113002
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发表时间:
2021-11-03
期刊:
影响因子:
6
通讯作者:
Pomiès P
Pomiès P
中科院分区:
生物学2区
文献类型:
--
作者:
Catteau M;Passerieux E;Blervaque L;Gouzi F;Ayoub B;Hayot M;Pomiès P

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在与慢性阻塞性肺疾病(COPD)相关的合并症中,骨骼肌无力和萎缩已知会影响患者的存活率。除了肌肉去条件反射,各种系统和内在因素与COPD肌肉功能障碍有关,但COPD肌肉对收缩的适应性受损从未被广泛研究过。我们将来自9名健康受试者和9名COPD患者的培养肌管置于耐力型电脉冲刺激(EPS)方案中。EPS可使COPD大鼠肌管内径、被覆表面缩小,MHC1表达减少。虽然蛋白质降解标记物的表达没有受到影响,但与健康的肌管相比,COPD患者EPS后蛋白质合成标记物mTOR的表达没有被诱导。分化标记物p16INK4a和p21的表达受损,而Myf5和MyoD的表达有受EPS影响的趋势。线粒体生物发生标志物Pg1、α和Mfn2的表达受到影响,而TFAM和COX1的表达与正常肌管相比有降低的趋势。与健康肌管相比,慢性阻塞性肺疾病患者的脂质过氧化反应增强,抗氧化酶SOD2和Gpx4的表达受到影响。因此,我们提供了COPD肌肉细胞对收缩反应受损的证据,这可能与COPD患者观察到的肌肉无力有关。
Among the comorbidities associated with chronic obstructive pulmonary disease (COPD), skeletal muscle weakness and atrophy are known to affect patient survival rate. In addition to muscle deconditioning, various systemic and intrinsic factors have been implicated in COPD muscle dysfunction but an impaired COPD muscle adaptation to contraction has never been extensively studied. We submitted cultured myotubes from nine healthy subjects and nine patients with COPD to an endurance-type protocol of electrical pulse stimulation (EPS). EPS induced a decrease in the diameter, covered surface and expression of MHC1 in COPD myotubes. Although the expression of protein degradation markers was not affected, expression of the protein synthesis marker mTOR was not induced in COPD compared to healthy myotubes after EPS. The expression of the differentiation markers p16INK4a and p21 was impaired, while expression of Myf5 and MyoD tended to be affected in COPD muscle cells in response to EPS. The expression of mitochondrial biogenesis markers PGC1α and MFN2 was affected and expression of TFAM and COX1 tended to be reduced in COPD compared to healthy myotubes upon EPS. Lipid peroxidation was increased and the expression of the antioxidant enzymes SOD2 and GPx4 was affected in COPD compared to healthy myotubes in response to EPS. Thus, we provide evidence of an impaired response of COPD muscle cells to contraction, which might be involved in the muscle weakness observed in patients with COPD.
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