Science Inventory

Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide

Citation:

Masood, S., E. Pennington, S. Simmons, P. Bromberg, S. Shaikh, R. Rice, A. Gold, Z. Zhang, AND J. Samet. Live cell imaging of oxidative stress in human airway epithelial cells exposed to isoprene hydroxyhydroperoxide. Redox Biology. Elsevier B.V., Amsterdam, Netherlands, 51:102281, (2022). https://doi.org/10.1016/j.redox.2022.102281

Impact/Purpose:

This manuscript reports on the molecular initiating mechanisms of secondary organic aerosols in an in vitro model of the human airway epithelium. 

Description:

Exposure to respirable air particulate matter (PM2.5) in ambient air is associated with morbidity and premature deaths. A major source of PM2.5 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 livecell imaging to monitor the effects of isoprene hydroxyhydroperoxides (ISOPOOH) in HAEC expressing roGFP2, a sensor of the glutathione redox potential (EGSH). Non-cytotoxic exposure of HAEC to ISOPOOH resulted in a rapid and robust increase in EGSH 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 ISOPOOHinduced 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. 

Record Details:

Record Type:DOCUMENT( JOURNAL/ PEER REVIEWED JOURNAL)
Product Published Date:05/01/2022
Record Last Revised:04/04/2022
OMB Category:Other
Record ID: 354463