Lipid Hydroperoxides as Mediators of Ozone-Induced Oxidative Changes in Human Airway Epithelial Cells

Human exposure to tropospheric ozone (O 3 ) is a significant public health concern. O 3 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 O 3 , leading to formation of free radicals, hydrogen peroxide (H 2 O 2 ), and lipid hydroperoxides. However, the role of these intermediates in mediating downstream cellular responses to O 3 inhalation is not well understood. Previous studies have observed an O 3 -induced increase in the glutathione redox potential (E GSH ) in human airway epithelial cells (HAEC). Impairment of mitochondrial respiration has also been previously observed in mice and rats exposed to O 3 . We hypothesized that lipid hydroperoxides contribute to these O 3 -induced oxidative changes in HAEC. In the present study we monitored the E GSH 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 H 2 O 2 in the observed hydroperoxide-induced changes. We found that exposure to the linoleic acid-derived hydroperoxide 9-HpODE induces dose-dependent increases in E GSH that are independent of H 2 O 2 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 O 3 inhalation. This abstract of a proposed presentation does not necessarily reflect EPA policy.