Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function
Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function
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DOI：
10.1152/ajplung.00304.2018
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发表时间：
2019-03-01
影响因子：
4.9
通讯作者：
Jaspers, Ilona
中科院分区：
文献类型：
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作者：
Clapp, Phillip W.;Lavrich, Katelyn S.;Jaspers, Ilona
香烟烟雾（CS）中的醛损害线粒体功能，降低纤毛搏动频率（CBF），导致粘膜纤毛清除率（MCC）降低。然而，醛类电子烟香料对CBF的影响尚不清楚。本研究的目的是研究肉桂醛（一种常用于电子烟的调味剂）是否会破坏线粒体功能并损害分化良好的人支气管上皮（hBE）细胞上的CBF。为此，将hBE细胞暴露于稀释的肉桂味电子液体和雾化气溶胶，并评估CBF的变化。hBE细胞随后暴露于不同浓度的肉桂醛，以建立对CBF影响的剂量-反应关系。采用Seahorse细胞外通量分析仪评价线粒体氧化磷酸化和糖酵解的变化，采用高效液相色谱法定量测定腺嘌呤核苷酸水平。含有肉桂醛的电子液体和蒸汽气溶胶都迅速但短暂地抑制CBF，并且单独暴露于肉桂醛重演了这种效果。肉桂醛损害线粒体呼吸和糖酵解的剂量依赖性的方式，和细胞内ATP水平显着，但暂时降低暴露后。添加尼古丁对桂皮醛诱导的CBF或线粒体功能抑制没有影响。这些数据表明，肉桂醛迅速破坏线粒体功能，抑制生物能量过程，并降低ATP水平，这与受损的CBF相关。由于正常的纤毛运动和MCC是必不可少的呼吸道防御，吸入肉桂醛可能会增加电子烟使用者呼吸道感染的风险。
Aldehydes in cigarette smoke (CS) impair mitochondrial function and reduce ciliary beat frequency (CBF), leading to diminished mucociliary clearance (MCC). However, the effects of aldehyde e-cigarette flavorings on CBF are unknown. The purpose of this study was to investigate whether cinnamaldehyde, a flavoring agent commonly used in e-cigarettes, disrupts mitochondrial function and impairs CBF on well-differentiated human bronchial epithelial (hBE) cells. To this end, hBE cells were exposed to diluted cinnamon-flavored e-liquids and vaped aerosol and assessed for changes in CBF. hBE cells were subsequently exposed to various concentrations of cinnamaldehyde to establish a dose-response relationship for effects on CBF. Changes in mitochondrial oxidative phosphorylation and glycolysis were evaluated by Seahorse Extracellular Flux Analyzer, and adenine nucleotide levels were quantified by HPLC. Both cinnamaldehyde-containing e-liquid and vaped aerosol rapidly yet transiently suppressed CBF, and exposure to cinnamaldehyde alone recapitulated this effect. Cinnamaldehyde impaired mitochondrial respiration and glycolysis in a dose-dependent manner, and intracellular ATP levels were significantly but temporarily reduced following exposure. Addition of nicotine had no effect on the cinnamaldehyde-induced suppression of CBF or mitochondrial function. These data indicate that cinnamaldehyde rapidly disrupts mitochondrial function, inhibits bioenergetic processes, and reduces ATP levels, which correlates with impaired CBF. Because normal ciliary motility and MCC are essential respiratory defenses, inhalation of cinnamaldehyde may increase the risk of respiratory infections in e-cigarette users.