| Title: | Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide |
| Author(s): | Masood S; Pennington ER; Simmons SO; Bromberg PA; Shaikh SR; Rice RL; Gold A; Zhang Z; Samet JM; |
| Address: | "Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA. National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Public Health and Integrated Toxicology Division, U.S. Environmental Protection Agency, Chapel Hill, NC, USA. Electronic address: samet.james@epa.gov" |
| DOI: | 10.1016/j.redox.2022.102281 |
| ISSN/ISBN: | 2213-2317 (Electronic) 2213-2317 (Linking) |
| Abstract: | "Exposure to respirable air particulate matter (PM(2.5)) in ambient air is associated with morbidity and premature deaths. A major source of PM(2.5) is the photooxidation of volatile plant-produced organic compounds such as isoprene. Photochemical oxidation of isoprene leads to the formation of hydroperoxides, environmental oxidants that lead to inflammatory (IL-8) and adaptive (HMOX1) gene expression in human airway epithelial cells (HAEC). To examine the mechanism through which these oxidants alter intracellular redox balance, we used live-cell imaging to monitor the effects of isoprene hydroxyhydroperoxides (ISOPOOH) in HAEC expressing roGFP2, a sensor of the glutathione redox potential (E(GSH)). Non-cytotoxic exposure of HAEC to ISOPOOH resulted in a rapid and robust increase in E(GSH) that was independent of the generation of intracellular or extracellular hydrogen peroxide. Our results point to oxidation of GSH through the redox relay initiated by glutathione peroxidase 4, directly by ISOPOOH or indirectly by ISOPOOH-generated lipid hydroperoxides. We did not find evidence for involvement of peroxiredoxin 6. Supplementation of HAEC with polyunsaturated fatty acids enhanced ISOPOOH-induced glutathione oxidation, providing additional evidence that ISOPOOH initiates lipid peroxidation of cellular membranes. These findings demonstrate that ISOPOOH is a potent environmental airborne hydroperoxide with the potential to contribute to oxidative burden of human airway posed by inhalation of secondary organic aerosols" |
| Keywords: | Butadienes Epithelial Cells/metabolism Glutathione/metabolism Hemiterpenes Humans Hydrogen Peroxide/pharmacology Oxidants/pharmacology Oxidation-Reduction *Oxidative Stress *Particulate Matter Air pollution Glutathione redox potential Lipid peroxidation L; |
| Notes: | "MedlineMasood, Syed Pennington, Edward R Simmons, Steven O Bromberg, Philip A Shaikh, Saame R Rice, Rebecca L Gold, Avram Zhang, Zhenfa Samet, James M eng P30 ES010126/ES/NIEHS NIH HHS/ T32 ES007126/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Netherlands 2022/03/21 Redox Biol. 2022 May; 51:102281. doi: 10.1016/j.redox.2022.102281. Epub 2022 Mar 15" |
