Khattri Ram B, Thome Trace, Fitzgerald Liam F, Wohlgemuth Stephanie E, Hepple Russell T, Ryan Terence E
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA.
Department of Physical Therapy and Muscle Biology, University of Florida, Gainesville, FL 32611, USA.
Toxics. 2022 Mar 14;10(3):140. doi: 10.3390/toxics10030140.
Tobacco smoke-related diseases such as chronic obstructive pulmonary disease (COPD) are associated with high healthcare burden and mortality rates. Many COPD patients were reported to have muscle atrophy and weakness, with several studies suggesting intrinsic muscle mitochondrial impairment as a possible driver of this phenotype. Whereas much information has been learned about muscle pathology once a patient has COPD, little is known about how active tobacco smoking might impact skeletal muscle physiology or mitochondrial health. In this study, we examined the acute effects of cigarette smoke condensate (CSC) on muscle mitochondrial function and hypothesized that toxic chemicals present in CSC would impair mitochondrial respiratory function. Consistent with this hypothesis, we found that acute exposure of muscle mitochondria to CSC caused a dose-dependent decrease in skeletal muscle mitochondrial respiratory capacity. Next, we applied an analytical nuclear magnetic resonance (NMR)-based approach to identify 49 water-soluble and 12 lipid-soluble chemicals with high abundance in CSC. By using a chemical screening approach in the Seahorse XF96 analyzer, several CSC-chemicals, including nicotine, o-Cresol, phenylacetate, and decanoic acid, were found to impair ADP-stimulated respiration in murine muscle mitochondrial isolates significantly. Further to this, several chemicals, including nicotine, o-Cresol, quinoline, propylene glycol, myo-inositol, nitrosodimethylamine, niacinamide, decanoic acid, acrylonitrile, 2-naphthylamine, and arsenic acid, were found to significantly decrease the acceptor control ratio, an index of mitochondrial coupling efficiency.
与烟草烟雾相关的疾病，如慢性阻塞性肺疾病（COPD），与高医疗负担和死亡率相关。据报道，许多COPD患者存在肌肉萎缩和无力，多项研究表明肌肉内在线粒体损伤可能是这种表型的驱动因素。虽然在患者已患COPD后已了解到许多关于肌肉病理学的信息，但对于主动吸烟如何影响骨骼肌生理学或线粒体健康却知之甚少。在本研究中，我们研究了香烟烟雾冷凝物（CSC）对肌肉线粒体功能的急性影响，并假设CSC中存在的有毒化学物质会损害线粒体呼吸功能。与该假设一致，我们发现肌肉线粒体急性暴露于CSC会导致骨骼肌线粒体呼吸能力呈剂量依赖性下降。接下来，我们应用基于分析核磁共振（NMR）的方法来鉴定CSC中高丰度的49种水溶性和12种脂溶性化学物质。通过在海马XF96分析仪中使用化学筛选方法，发现几种CSC化学物质，包括尼古丁、邻甲酚、苯乙酸和癸酸，会显著损害小鼠肌肉线粒体分离物中ADP刺激的呼吸。此外，还发现几种化学物质，包括尼古丁、邻甲酚、喹啉、丙二醇、肌醇、亚硝基二甲胺、烟酰胺、癸酸、丙烯腈、2-萘胺和砷酸，会显著降低接受者控制率，这是线粒体偶联效率的一个指标。
