1 Department of Critical Care and.
Am J Respir Crit Care Med. 2013 Dec 1;188(11):1313-20. doi: 10.1164/rccm.201304-0732OC.
Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to protein degradation.
To investigate whether autophagy is enhanced in locomotor muscles of stable patients with COPD, to quantify autophagy-related gene expression in these muscles, and to identify mechanisms of autophagy induction.
Muscle biopsies were obtained from two cohorts of control subjects and patients with COPD and the numbers of autophagosomes in the vastus lateralis and tibialis anterior muscles, the levels of LC3B protein lipidation, and the expression of autophagy-related genes were measured in the vastus lateralis muscle. To investigate potential pathways that might induce the activation of autophagy, measures were taken of protein kinase B (AKT), mTORC1, and AMPK pathway activation, transcription factor regulation, proteasome activation, and oxidative stress.
Autophagy is enhanced in the locomotor muscles of patients with COPD as shown by significantly higher numbers of autophagosomes in affected muscles as compared with control subjects. Autophagosome number inversely correlates with FEV1. In the vastus lateralis, LC3B protein lipidation is increased by COPD and the expression of autophagy-related gene expressions is up-regulated. LC3B lipidation inversely correlates with thigh cross-sectional area, FEV1, and FEV1/FVC ratio. Enhanced autophagy is associated with activation of the AMPK pathway and FOXO transcription factors, inhibition of the mTORC1 and AKT pathways, and the development of oxidative stress.
Autophagy is significantly enhanced in locomotor muscles of stable patients with COPD. The degree of autophagy correlates with severity of muscle atrophy and lung function impairment.
慢性阻塞性肺疾病（COPD）患者的运动肌肉萎缩部分是由于泛素-蛋白酶体系统增加了蛋白质降解。目前尚不清楚自噬是否也有助于蛋白质降解。
研究稳定期 COPD 患者运动肌肉中自噬是否增强，定量这些肌肉中的自噬相关基因表达，并确定自噬诱导的机制。
从两组对照受试者和 COPD 患者中获取肌肉活检，并测量股外侧肌和胫骨前肌中自噬体的数量、LC3B 蛋白脂质化水平以及自噬相关基因的表达。为了研究可能诱导自噬激活的潜在途径，测量了蛋白激酶 B（AKT）、mTORC1 和 AMPK 途径的激活、转录因子调节、蛋白酶体激活和氧化应激。
与对照组相比，COPD 患者的运动肌肉中自噬增强，受影响肌肉中的自噬体数量明显更高。自噬体数量与 FEV1 呈负相关。在股外侧肌中，LC3B 蛋白脂质化增加与 COPD 有关，自噬相关基因表达上调。LC3B 脂质化与大腿横截面积、FEV1 和 FEV1/FVC 比值呈负相关。增强的自噬与 AMPK 途径和 FOXO 转录因子的激活、mTORC1 和 AKT 途径的抑制以及氧化应激的发展有关。
稳定期 COPD 患者的运动肌肉中自噬明显增强。自噬的程度与肌肉萎缩和肺功能损伤的严重程度相关。
