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Real-Time Redox Adaptations in Human Airway Epithelial Cells Exposed to Isoprene Hydroxy Hydroperoxide
Citation:
Pennington, E., S. Masood, S. Simmons, L. Dailey, P. Bromberg, R. Rice, A. Gold, Z. Zhang, W. Wu, Y. Yang, AND J. Samet. Real-Time Redox Adaptations in Human Airway Epithelial Cells Exposed to Isoprene Hydroxy Hydroperoxide. Redox Biology. Elsevier B.V., Amsterdam, Netherlands, 61(102646):1, (2023). https://doi.org/10.1016/j.redox.2023.102646
Impact/Purpose:
This manuscript reveals rapid redox adaptations involved in the cellular response to isoprene hydroxy hydroperoxide and provides a live view of the dynamic regulation of redox homeostasis in human airway cells.
Description:
While redox processes play a vital role in maintaining intracellular homeostasis by regulating critical signaling and metabolic pathways, supra-physiological or sustained oxidative stress can lead to adverse responses or cytotoxicity. Inhalation of ambient air pollutants such as particulate matter and secondary organic aerosols (SOA) induces oxidative stress in the respiratory tract through mechanisms that remain poorly understood. We investigated the effect of isoprene hydroxy hydroperoxide (ISOPOOH), an atmospheric oxidation product of vegetation-derived isoprene and a constituent of SOA, on intracellular redox homeostasis in cultured human airway epithelial cells (HAEC). We used high-resolution live cell imaging of HAEC expressing the genetically encoded ratiometric biosensors Grx1-roGFP2, iNAP1, or HyPer, to assess changes in the cytoplasmic glutathione redox potential (EGSH), and levels of NADPH and H2O2, respectively. Non-cytotoxic exposure to ISOPOOH resulted in dose-dependent induction of EGSH in HAEC that was markedly potentiated by prior glucose deprivation. ISOPOOH-induced changes in EGSH were accompanied by concomitant decreases in intracellular NADPH levels. Following ISOPOOH exposure, the introduction of glucose resulted in a rapid restoration of baseline EGSH and NADPH levels, while the glucose analog 2-deoxyglucose resulted in inefficient restoration of EGSH and NADPH levels. To elucidate bioenergetic adaptations involved in combatting ISOPOOH-induced oxidative stress we investigated the regulatory role of glucose-6-phosphate dehydrogenase (G6PD). A knockout of G6PD markedly impaired glucose-mediated recovery of EGSH but not NADPH levels. These findings reveal rapid redox adaptations involved in the cellular response to ISOPOOH and provide a live view of the dynamic regulation of redox homeostasis in human airway cells as they are exposed to environmental oxidants.
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DOI: Real-Time Redox Adaptations in Human Airway Epithelial Cells Exposed to Isoprene Hydroxy Hydroperoxide