An Integrated Imaging Approach to the Study of the Oxidant Effects of Air Pollutions on Human Lung Cells

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  • March 22, 2019
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  • Cheng, Wan-Yun
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • Air pollution is one of the most common environmental exposures imposed on humans in urban areas on a daily basis. Molecular toxicology studies of the inflammatory effects of ambient air pollutants typically focus on the activation of signaling events that lead to the transcriptional activation of relevant inflammatory genes. While there is a growing body of evidence that oxidative stress plays a critical role in adverse responses induced by a broad array of environmental agents, an integration of the study of oxidant effects in mechanistic studies is hampered by methodological shortcomings and limitations such as sensitivity and specificity. The causative relationship between signaling pathways and adverse outcomes stimulated by specific ambient contaminants has been described. In addition, the generation of oxidative stress has been implicated as an initiating event that leads to adverse responses triggered by exposure to environmental toxicants. However, due to their transient nature, reactivity, and low abundance, detection of reactive oxygen species (ROS) is methodologically challenging. The application of new genetically encoded reporters provides the opportunity to interface real-time measurement of oxidative stress into mechanistic studies with increased temporal and spatial resolution. The studies herein are aimed at integrating imaging analyses of oxidative stress endpoints in molecular signaling of the inflammatory effects of environmental oxidants. We conducted a study using zinc and 1,2-naphthoquinone as model toxicants to (1) develop an integrated imaging method for measurement of redox potential, ROS levels, and mitochondrial dysfunction; (2) examine the role of oxidative stress in the initiation of signaling events that lead to inflammatory gene expression; and (3) create an advanced imaging method to perform simultaneous measurements of redox changes and ROS production.
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  • In Copyright
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  • ... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Environmental Sciences and Engineering.
Advisor
  • Samet, James
Degree granting institution
  • University of North Carolina at Chapel Hill
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