NMR Spectroscopy Identifies Chemicals in Cigarette Smoke Condensate That Impair Skeletal Muscle Mitochondrial Function.
NMR Spectroscopy Identifies Chemicals in Cigarette Smoke Condensate That Impair Skeletal Muscle Mitochondrial Function.
复制标题
DOI：
10.3390/toxics10030140
复制
发表时间：
2022-03-14
期刊：
影响因子：
4.6
通讯作者：
Ryan TE
中科院分区：
文献类型：
--
作者：
Khattri RB;Thome T;Fitzgerald LF;Wohlgemuth SE;Hepple RT;Ryan TE
慢性阻塞性肺病（COPD）等与烟草烟雾相关的疾病与高医疗负担和死亡率有关。据报道，许多慢性阻塞性肺病患者有肌肉萎缩和无力，一些研究表明内在的肌肉线粒体损伤可能是这种表型的驱动因素。尽管对于患有慢性阻塞性肺病的患者的肌肉病理学了解很多，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。在这项研究中，我们检查了香烟烟雾冷凝物 (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。与这一假设一致，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，我们应用基于核磁共振 (NMR) 的分析方法来鉴定 CSC 中丰度较高的 49 种水溶性和 12 种脂溶性化学物质。通过在 Seahorse 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、苯乙酸盐和癸酸）会显着损害小鼠肌肉线粒体分离物中 ADP 刺激的呼吸。除此之外，还发现包括尼古丁、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-萘胺和砷酸在内的几种化学物质会显着降低受体控制比（线粒体偶联效率的指标）。
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.
登录
查看更多内容
影响因子：
2
作者：
Arndt, Daniel;Wachsmuth, Christian;Bentley, Mark
通讯作者：
Bentley, Mark
影响因子：
3.4
作者：
Das, Subhasis;Gautam, N.;Roy, Somenath
通讯作者：
Roy, Somenath
影响因子：
4.6
作者：
Darabseh MZ;Maden-Wilkinson TM;Welbourne G;Wüst RCI;Ahmed N;Aushah H;Selfe J;Morse CI;Degens H
通讯作者：
Degens H
影响因子：
5.5
作者：
Broxterman, Ryan M.;Hoff, Jan;Richardson, Russell S.
通讯作者：
Richardson, Russell S.
影响因子：
3.7
作者：
Cheung, Kwok-Kuen;Fung, Timothy Kai-Hang;Ngai, Shirley P. C.
通讯作者：
Ngai, Shirley P. C.