Division of Pulmonary and Critical Care Medicine and.
Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York.
Am J Respir Cell Mol Biol. 2021 Sep;65(3):259-271. doi: 10.1165/rcmb.2020-0551OC.
Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force generation capacity, which partially depends on fibers' oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of SDHC (succinate dehydrogenase subunit C) in association with lower oxygen consumption and fatigue tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema, and we found that SDHC is required to support respiration in cultured muscle cells. Moreover, gain of SDH function in emphysema animals' muscles resulted in better oxygen consumption rate and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers and a reduced amount of 2B fibers. Our data suggest that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful in developing strategies aimed at attenuating this comorbidity.
肺气肿患者常出现运动肌肉功能障碍，这与该人群的残疾和更高死亡率独立相关。肌肉功能障碍包括肌力产生能力下降，这部分取决于纤维的氧化能力，但很少有针对肺气肿肌肉呼吸的机制研究。我们使用最近建立的肺气肿驱动的骨骼肌功能障碍动物模型，发现与运动肌肉耗氧量降低和疲劳耐受性降低相关的 SDHC（琥珀酸脱氢酶亚基 C）下调。先前在肺气肿患者的肌肉中观察到 SDH 活性降低，我们发现 SDHC 是支持培养的肌肉细胞呼吸所必需的。此外，在肺气肿动物的肌肉中获得 SDH 功能可导致更高的耗氧率和疲劳耐受性。这些变化与更多相对更氧化的 2-A 和 2X 型纤维数量增加以及 2B 型纤维数量减少相关。我们的数据表明，SDHC 是肺气肿驱动的骨骼肌呼吸和疲劳性的关键调节因子，这可能对制定旨在减轻这种合并症的策略具有重要意义。
