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Characterization of the Impacts of the Interactions between Particulate Matter and Ozone on Protein Responses in Rat Lung and Aorta Tissues
Citation:
Bruno, M. AND Y. Ge. Characterization of the Impacts of the Interactions between Particulate Matter and Ozone on Protein Responses in Rat Lung and Aorta Tissues. SETAC, Denver, Colorado, September 06 - 08, 2017.
Impact/Purpose:
For risk assessment purpose, there is an urgent need to develop novel methodologies and approaches for efficient analysis of chemical interactions in mixtures and toxic mechanisms associated with exposure to the chemical mixtures.This study provides an integrated novel approach using two Proteomics platforms for characterization of toxicity pathways/ proteins associated with PM/Ozone chemical mixtures.
Description:
To get a better understanding of how multiple air pollutants of different sources interact, and of the molecular pathways and biological mechanisms underlying these interactions, it is critical to develop effective risk assessment approaches/methodologies/framework for characterization of toxicity and adverse health effects of air multipollutant mixtures. To accomplish this goal, we performed a proteomic study to characterize the impacts of the interactions between particulate matter (PM) and ozone (O3) on expression and/or phosphorylation levels of some protein biomarkers, critical signaling proteins, and inflammatory cytokines involved in PM and O3-mediated toxicity pathways in lung and aorta tissues of SH hypertensive rats exposed to PM and O3, singly and in combinations using multiplexed ELISA and a protein array. Multivariate statistical analysis and mathematical modeling of the PM and O3-mediated proteomic response patterns was performed to identify the correlations between protein expression/phosphorylation and toxicity or pathology responses to PM, O3, and their combinations. For example, PM increased expressions of inflammatory cytokines such as IL-6 and Rage in lung and CCL11 in aorta tissues, whereas O3 increased expressions of the cytokines such as Eotaxin, IL-RA, and IL-2RA in lung and IL-10 in aorta tissues, and the mixtures of PM and O3 altered expressions of cytokines such as CCL5, BDNF, and HGF. Our results demonstrated that proteomic responses in response to exposures of PM, O3, and their mixtures vary in different tissues, in importance in relation to different components of the mixtures, in pathways activated, and in causing different toxicity effects.