Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Efron St., 9649, Bat Galim, Haifa, 31096, Israel.
Adv Exp Med Biol. 2013;788:7-17. doi: 10.1007/978-94-007-6627-3_2.
Cigarette smoking has been identified as a risk factor for muscular damage and sarcopenia, the age-related loss of muscle mass and strength in old age. Cigarette smoke (CS)-induced oxidative stress and p38 MAPK activation have been shown to be the main cellular mechanisms leading to skeletal muscle catabolism. In order to investigate the involvement of NF-κB as another possible cellular mechanism by which CS promotes muscle catabolism, C2 myotubes, from an in vitro skeletal muscle cell line, were exposed to different time periods of whole vapor phase CS in the presence or absence of NF-κB inhibitor, IMD-0354. The CS-induced reduction in diameter of myotubes and time-dependent degradation of the main contractile protein myosin heavy chain were abolished by NF-κB inhibition. Also, C2 exposure to CS resulted in IκB-α degradation and NF-κB activation, which led to upregulation of the muscle specific E3 ubiquitin ligase MuRF1, but not MAFbx/atrogin-1. In conclusion, our results demonstrate that vapor phase CS exposure to skeletal myotubes triggers NF-κB activation leading to skeletal muscle cell damage and breakdown of muscle proteins mediated by muscle specific E3 ubiquitin ligase MuRF1. Our findings provide another possible molecular mechanism for the catabolic effects of CS in skeletal muscle.
吸烟已被确定为肌肉损伤和肌肉减少症（衰老相关的肌肉质量和力量损失）的危险因素。已经表明，香烟烟雾（CS）引起的氧化应激和 p38 MAPK 激活是导致骨骼肌分解代谢的主要细胞机制。为了研究 NF-κB 是否作为 CS 促进肌肉分解代谢的另一种可能的细胞机制，用体外骨骼肌细胞系 C2 肌管来研究 CS 对 NF-κB 抑制剂 IMD-0354 存在或不存在时的不同时间段的全蒸气相 CS 进行了暴露。NF-κB 抑制消除了 CS 诱导的肌管直径减小和肌球蛋白重链的时间依赖性降解。此外，C2 暴露于 CS 导致 IκB-α 降解和 NF-κB 激活，导致肌肉特异性 E3 泛素连接酶 MuRF1 的上调，但不是 MAFbx/atrogin-1。总之，我们的结果表明，蒸气相 CS 暴露于骨骼肌肌管会触发 NF-κB 激活，从而导致骨骼肌细胞损伤和肌肉蛋白的分解，这是由肌肉特异性 E3 泛素连接酶 MuRF1 介导的。我们的发现为 CS 在骨骼肌中的分解代谢作用提供了另一种可能的分子机制。
