Kishta Osama A, Guo Yeting, Mofarrahi Mahroo, Stana Flavia, Lands Larry C, Hussain Sabah N A
Respiratory Division, Department of Medicine, Montréal Children's Hospital, McGill University Health Centre, Montréal, QC, Canada.
Department of Pediatrics, McGill University, Montréal, QC, Canada.
Food Nutr Res. 2017 Jun 1;61(1):1325309. doi: 10.1080/16546628.2017.1325309. eCollection 2017.
: Pulmonary infection in cystic fibrosis patients is associated with skeletal muscle atrophy. In this study, we investigated the effects of infection and a whey protein-rich diet on skeletal muscle proteolytic pathways. : An agar bead model of pulmonary infection was established in adult C57/Bl6 mice. Protein ubiquitinaiton, lipidation of LC3B protein and expressions of autophagy-related genes and ubiquitin E3 ligases were quantified using immunoblotting and qPCR. The effects of pressure-treated whey protein diet on muscle proteolysis were also evaluated. : Pulmonary infection reduced diaphragm, tibialis anterior, and soleus muscle weights and increased protein ubiquitination, LC3B protein lipidation, and the expressions of , , , , and genes in each muscle. These changes were greater in the tibialis as compared to soleus and diaphragm. Proteolysis indicators increased within one day of infection but were not evident after seven days of infection. A pressurized whey diet attenuated LC3B protein lipidation, expressions of autophagy-related genes (BNIP3), pro-inflammatory cytokines, and protein ubiquitination. : We conclude that pulmonary infection activates the autophagy, and the proteasome pathways in skeletal muscles and that a pressurized whey protein diet attenuates muscle proteolysis in this model.
囊性纤维化患者的肺部感染与骨骼肌萎缩有关。在本研究中,我们调查了感染和富含乳清蛋白的饮食对骨骼肌蛋白水解途径的影响。:在成年C57/Bl6小鼠中建立肺部感染的琼脂珠模型。使用免疫印迹和qPCR对蛋白质泛素化、LC3B蛋白的脂化以及自噬相关基因和泛素E3连接酶的表达进行定量。还评估了经压力处理的乳清蛋白饮食对肌肉蛋白水解的影响。:肺部感染降低了膈肌、胫前肌和比目鱼肌的重量,并增加了各肌肉中的蛋白质泛素化、LC3B蛋白脂化以及ATG5、ATG7、BNIP3、LC3B和p62基因的表达。与比目鱼肌和膈肌相比,这些变化在胫前肌中更大。蛋白水解指标在感染后一天内增加,但在感染七天后不明显。加压乳清饮食减弱了LC3B蛋白脂化、自噬相关基因(BNIP3)的表达、促炎细胞因子和蛋白质泛素化。:我们得出结论,肺部感染激活了骨骼肌中的自噬和蛋白酶体途径,并且加压乳清蛋白饮食在该模型中减弱了肌肉蛋白水解。