Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse
Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse
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DOI：
10.1152/japplphysiol.00788.2017
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发表时间：
2018-04-01
影响因子：
3.3
通讯作者：
Richardson, Russell S.
中科院分区：
文献类型：
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作者：
Gifford, Jayson R.;Trinity, Joel D.;Richardson, Russell S.
慢性阻塞性肺疾病 (COPD) 患者表现出骨骼肌线粒体表型改变，通常包括线粒体密度降低。呼吸功能改变，氧化应激升高。由于这种表型可以用通常伴随这种疾病的久坐生活方式来解释，因此本研究的目的是确定当慢性阻塞性肺病患者与客观测量的体力活动（PA；加速测量）相匹配的对照受试者进行比较时，这种改变是否仍然明显。对从 9 名 COPD 患者和 9 名 PA 匹配对照受试者 (CON) 的股外侧肌活检的肌纤维中评估线粒体密度 [柠檬酸合酶 (CS) 活性]、呼吸功能（在可渗透纤维中进行呼吸测量）和肌肉氧化应激 [4-羟基壬烯醛 (4-HNE) 含量] 的指标。尽管执行相似的 PA 水平（CON：18 +/- 3，COPD：每天 20 +/- 7 分钟中度至剧烈 PA；CON：4,596 +/- 683，COPD：每天 4,219 +/- 763 步，P > 0.70）。 COPD 患者的线粒体表型仍表现出一些改变，包括骨骼肌线粒体密度减弱（CS 活性；CON 70.6 +/- 3.8。COPD 52.7 +/- 6.5 11/mg，P < 0.05）、线粒体呼吸改变[例如，复合物 I 驱动的状态 3 与复合物 II 驱动的状态 3 的比率 (CI/CII)：CON： 1.20 +/- 0.11，COPD：0.90 +/- 0.05，P < 0.05）和氧化应激（4-HNE：CON：1.35 +/- 0.19，COPD：2.26 +/- 0.25，相对于 β-肌动蛋白，P < 0.05）。此外。 CS 活性 (r = 0.55)、CI/CII (r = 0.60) 和 4-HNE (r = 0.49) 均与肺功能相关，肺功能以 1 秒用力呼气量进行评估 (P < 0.05)，但与 PA 无关 (P > 0.05)。总之，即使在没有不同水平的 PA 的情况下，COPD 中线粒体表型的改变也存在，并且似乎与疾病本身有关。新的和值得注意的慢性阻塞性肺疾病 (COPD) 与骨骼肌线粒体功能的衰弱性改变有关。通过将慢性阻塞性肺病患者的线粒体表型与每天进行相同量体力活动的健康对照受试者的线粒体表型进行比较，这项研究提供了证据，表明在慢性阻塞性肺病中观察到的功能失调的线粒体表型的许多方面不仅是由于体力活动减少，而且可能与疾病本身有关。
Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density. altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in penneabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 +/- 3, COPD: 20 +/- 7 daily minutes moderate-to-vigorous PA; CON: 4,596 +/- 683, COPD: 4,219 +/- 763 steps per day, P > 0.70). patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 +/- 3.8. COPD 52.7 +/- 6.5 11/mg, P < 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII): CON: 1.20 +/- 0.11, COPD: 0.90 +/- 0.05, P < 0.05), and oxidative stress (4-HNE: CON: 1.35 +/- 0.19, COPD: 2.26 +/- 0.25 relative to beta-actin, P < 0.05). Furthermore. CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P < 0.05), but not PA (P > 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself.NEW & NOTEWORTHY Chronic obstructive pulmonary disease (COPD) is associated with debilitating alterations in the function of skeletal muscle mitochondria. By comparing the mitochondrial phenotype of patients with COPD to that of healthy control subjects who perform the same amount of physical activity each day, this study provides evidence that many aspects of the dysfunctional mitochondrial phenotype observed in COPD are not merely due to reduced physical activity but are likely related to the disease itself.