Ultrafine Particulates Differentially Induce Reactive Oxygen Species in Fibroblast BHK21 and A549 Human Alveolar Lung Cells
Mentor:Jay Brewster, Professor of Biology, Associate Provost, Pepperdine University
The signaling of cell stress in response to organelle dysfunction, toxin exposure, and mutation is complex; generating responses that can include adaptation or in severe cases cellular apoptosis. This project focuses upon the cellular mobilization of reactive oxygen species (ROS) as a signaling response to stress. Antioxidant compounds, such as reduced glutathione (GSH), Curcumin, and Baicalein have been shown to suppress pro-apoptosis signals under some types of stress. In this project we assessed cultured fibroblast and lung alveolar cells exposed to stressors that include the endoplasmic reticulum (ER) toxins, and ultrafine particles that are known to activate cell death. In fibroblasts exposed to ER stress, neither ROS mobilization nor protection by antioxidants was observed. The antioxidant Baicalein was shown to exhibit cytotoxicity in concentrations above 1uM. In cultured human lung alveolar cells (A549) exposure to ER stress resulted in mobilization of significant levels in ROS, similar to those observed by cellular exposure to tert-butyl hydrogen peroxide (positive control). This difference between fibroblast cells and alveoloar cells denotes an interesting differential response to ER stress. Ultra fine carbon black particulates were shown to induce elevated ROS in both fibroblasts and alveolar cells. Subsequent experiments will include an analysis of antioxidants upon the survival of ER stressed alveolar cells.