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The Role of Lipid Hydroperoxides in Ozone-Induced Increases in Glutathione Redox Potential in Human Airway Epithelial Cells
Citation:
Corteselli, E. AND J. Samet. The Role of Lipid Hydroperoxides in Ozone-Induced Increases in Glutathione Redox Potential in Human Airway Epithelial Cells. Society of Toxicology, Baltimore, MD, March 12 - 17, 2017.
Impact/Purpose:
This is an abstract of a proposed presentation to the 2017 Annual Meeting of the Society of Toxicology. The works describes biochemical effects of the oxidative stress caused by ozone exposure in human lung cells
Description:
Human exposure to tropospheric ozone pollution is of global public health concern. Exposure to ozone induces functional decrements and inflammatory responses in the respiratory tract that are thought to occur through oxidative mechanisms. While it is known that ozone oxidizes polyunsaturated fatty acids to produce lipid hydroperoxides, the role of these hydroperoxides in mediating cellular responses to ozone inhalation is not well understood. Previous live cell imaging studies have found a marked ozone-induced increase in the glutathione redox potential (EGSH), reflecting the ratio of reduced to oxidized glutathione (GSH/GSSG), in human airway epithelial cells (HAEC) expressing the genetically encoded fluorogenic sensor of EGSH roGFP. roGFP reportedly senses EGSH by equilibrating with the GSH/GSSG through a redox relay that is initiated by H2O2. While the previous O3 study also found an increase in H2O2, observed using another fluorogenic sensor (HyPer), its contribution to the O3 –induced increase to the EGSH was unclear. We therefore hypothesized that lipid hydroperoxides contribute to increases in EGSH during O3 exposure. In the present study we used live cell confocal imaging to monitor BEAS-2B cells expressing roGFP or HyPer as they were exposed in real time to lipid hydroperoxides or the corresponding hydroxides. Exposure to the organic tert-butyl hydroperoxide or the linoleic hydroperoxide 13-(S) HpODE induced dose-dependent increases in EGSH, reported by roGFP, that were comparable in magnitude to that observed during exposure to 0.5 ppm O3. Exposure to the hydroxide 13-(S)-HODE did not have a significant effect on EGSH, indicating that the peroxy group is necessary to cause the increase in cytosolic EGSH. Dose-dependent H2O2 production, reported by HyPer, was observed during exposure to 13-(S)-HpODE. Analysis of lactate dehydrogenase release revealed that no significant cytotoxicity occurred from exposure to these hydroperoxides or hydroxides during these experiments. These results suggest that production of lipid hydroperoxides is an initiating event that leads to the loss of reducing redox potentials induced by exposure of HAEC to O3. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.