Signatures of Oxidative Stress Associated with Inhaled Nanomaterials
Proteomics and expression arrays will be used to identify molecular signatures indicative of specific sources of reactive oxygen species (ROS), the generation of which is believed to be a key component in pulmonary toxicity associated with nPM exposure. Signatures will be used to characterize underlying sources of ROS to better understand the mechanisms of pulmonary toxicity and to validate results from proteomic and gene expression data in related PNNL nPM projects.
This project will target metabolically active cells (alveolar type 2 cells) that are sensitive to nPM surface chemistry. In initial studies, DNA microarrays and proteomics will be used to evaluate responses to oxidative stress associated with nPM exposure looking specifically at gene expression, protein levels and extracellular protein release in cultured C10 alveolar type 2 cells. Proteins identified will be further quantitated using ELISA microarrays where the focus will be to study the detailed time-course and dose-response. This will lead to more detailed models of cell signaling pathways that are activated by ROS. Final studies will evaluate biomarkers of nPM exposure and oxidative stress in bronchiolar lavage samples from mice and humans where the exposure is cigarette smoke.
Point of Contact: Terri Stewart