Inhalation of nicotine with flavors using e-cigarettes is a widespread and increasing practice. The acute and chronic effects of this exposure on the epithelial cells which form the barrier protecting the airways and alveolar space are poorly understood. Emerging findings indicate that respiratory epithelial cell dysfunction, death and the development of lung diseases are initiated by injury to the mitochondria (1, 2). However, the effect of aerosolized nicotine with fruit and dessert flavors in e-cigarettes on mitochondrial function in these cells remain poorly understood (3). We will study the cells that are the first exposed to e-cigarette aerosols. We will use human and murine primary airway epithelial cells (AEC), which are the first line
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It has been reported that e-cigarette aerosols are also deposited in the alveolar space (5). Therefore we will also use human and murine primary ATII cells in our study. Our Preliminary Data obtained from AEC and ATII cells demonstrate that aerosolized nicotine delivered by e-cigarettes in concentrations which mimic e-cigarette use in humans induces mitochondrial dysfunction and reactive oxygen species (ROS) generation. Moreover, we also found that e-cigarette aerosol with cherry flavors contains diacetyl and benzaldehyde by mass spectrometry analysis, which may cause epithelial respiratory injury. Nicotine with cherry and chocolate flavors in e-cigarettes caused cytokine release, cell apoptosis and oxidative stress in human primary AEC and ATII cells (Preliminary Data). This suggests the impairment of antioxidant defense system. DJ-1 is a chaperone-like protein localized in the mitochondria, cytoplasm and nucleus and protects cells from oxidative stress via scavenging ROS (6). DJ-1 also serves as a sensor of redox status (6). DJ-1 with irreversible oxidation of cysteine at position 106 (Cys-106) to sulfonic acid losses its cytoprotective …show more content…
In this project, we will determine the effect of e-cigarette aerosol on human primary AEC and ATII cells in vitro and in vivo. We hypothesize that aerosolized nicotine with fruit or dessert flavors induces mitochondrial dysfunction, primary AEC and ATII cell injury and that oxidation or loss of DJ-1 exacerbates their effect. We propose to use mechanistic approaches to examine the role of DJ-1 in human AEC and ATII cells in vitro. We will validate our results using both cell types isolated from DJ-1 knockout mice. We have studied the effect of environmental exposure on primary human and murine AEC and ATII cells
It has been reported that e-cigarette aerosols are also deposited in the alveolar space (5). Therefore we will also use human and murine primary ATII cells in our study. Our Preliminary Data obtained from AEC and ATII cells demonstrate that aerosolized nicotine delivered by e-cigarettes in concentrations which mimic e-cigarette use in humans induces mitochondrial dysfunction and reactive oxygen species (ROS) generation. Moreover, we also found that e-cigarette aerosol with cherry flavors contains diacetyl and benzaldehyde by mass spectrometry analysis, which may cause epithelial respiratory injury. Nicotine with cherry and chocolate flavors in e-cigarettes caused cytokine release, cell apoptosis and oxidative stress in human primary AEC and ATII cells (Preliminary Data). This suggests the impairment of antioxidant defense system. DJ-1 is a chaperone-like protein localized in the mitochondria, cytoplasm and nucleus and protects cells from oxidative stress via scavenging ROS (6). DJ-1 also serves as a sensor of redox status (6). DJ-1 with irreversible oxidation of cysteine at position 106 (Cys-106) to sulfonic acid losses its cytoprotective …show more content…
In this project, we will determine the effect of e-cigarette aerosol on human primary AEC and ATII cells in vitro and in vivo. We hypothesize that aerosolized nicotine with fruit or dessert flavors induces mitochondrial dysfunction, primary AEC and ATII cell injury and that oxidation or loss of DJ-1 exacerbates their effect. We propose to use mechanistic approaches to examine the role of DJ-1 in human AEC and ATII cells in vitro. We will validate our results using both cell types isolated from DJ-1 knockout mice. We have studied the effect of environmental exposure on primary human and murine AEC and ATII cells