Alveolar Epithelial Cell Dysfunction Induced By Flavored E-Cigarette Aerosols

摘要 电子烟装置从含有调味剂、尼古丁和媒介物的电子液体产生气溶胶。吸入性e- 香烟烟雾可以到达肺泡区域。肺泡II型（ATII）细胞产生和分泌肺 表面活性剂，降低表面张力。它们还具有干细胞潜能，可以增殖和修复 损伤后的上皮细胞导致肺再生。由于其功能和位置要求高， 在肺中，它们高度依赖于线粒体。线粒体DNA缺乏组蛋白，作为屏障， 有害因素，导致其易受损害。线粒体功能障碍可导致线粒体自噬 ATII细胞死亡。我们在父R 01补助金和本申请中的初步结果表明， 具有水果和甜点风味的电子烟气溶胶对人类原代ATII细胞的影响。这个目标 行政补充提案旨在进一步阐明性别对人类原发性ATII细胞功能障碍的影响 是由暴露于调味成分和电子烟气溶胶引起的。在目标1中，我们将比较DNA损伤 在ATII细胞中暴露于调味成分和具有水果和甜点风味的电子烟气溶胶中。在目标2中， 将定义这种暴露对ATII细胞中线粒体功能的影响。获得的结果将定义性别 调味成分和电子烟气溶胶对呼吸道损伤风险的影响。

Abstract E-cigarette devices produce an aerosol from e-liquids containing flavorings, nicotine, and vehicle. Inhaled e- cigarette aerosol can reach the alveolar region. Alveolar type II (ATII) cells produce and secrete pulmonary surfactant, which decreases surface tension. They also have a stem cell potential, proliferate and repair the epithelium after damage leading to lung regeneration. Due to their energy-demanding functions and location in the lung, they depend highly on mitochondria. Mitochondrial DNA lacks histones that serve as a barrier against damaging factors, contributing to its susceptibility to damage. Mitochondrial dysfunction can lead to mitophagy and ATII cell death. Our preliminary results in the parent R01 grant and this application demonstrate the harmful effect of e-cigarette aerosols with fruit and dessert flavors on human primary ATII cells. The goal of this administrative supplement proposal is to clarify further the sex influences on human primary ATII cell dysfunction caused by exposure to flavored constituents and e-cigarette aerosols. In Aim 1, we will compare DNA damage in ATII cells exposed to flavored constituents and e-cigarette aerosols with fruit and dessert flavors. In Aim 2, we will define the impact of this exposure on mitochondrial function in ATII cells. Obtained results will define sex influences on the respiratory injury risk of flavored constituents and e-cigarette aerosols.