LAUSR

Human exposure to tropospheric ozone (O3) is a significant public health concern. O3 inhalation induces airway inflammation and pulmonary function decrements, and may also lead to cardiovascular morbidity. The carbon-carbon double bonds in polyunsaturated fatty acids are primary targets for oxidation by O3, leading to formation of free radicals, hydrogen peroxide (H2O2), and lipid hydroperoxides. However, the role of these intermediates in mediating downstream cellular responses to O3 inhalation is not well understood. Previous studies have observed an O3-induced increase in the glutathione redox potential (EGSH) in human airway epithelial cells (HAEC). Impairment of mitochondrial respiration has also been previously observed in mice and rats exposed to O3. We hypothesized that lipid hydroperoxides contribute to these O3-induced oxidative changes in HAEC. In the present study we monitored the EGSH using the fluorogenic sensor roGFP and mitochondrial respiration with the Seahorse Extracellular Flux Analyzer in BEAS-2B cells exposed to lipid hydroperoxides. Overexpression of catalase was used to evaluate the role of H2O2 in the observed hydroperoxide-induced changes. We found that exposure to the linoleic acid-derived hydroperoxide 9-HpODE induces dose-dependent increases in EGSH that are independent of H2O2 production. Exposure to 9-HpODE also caused a decrease in mitochondrial basal oxygen consumption, maximal respiration, and spare respiratory capacity. These results suggest that lipid hydroperoxides are primary effectors of oxidative changes induced by O3 inhalation. This abstract of a proposed presentation does not necessarily reflect EPA policy.