Effect of titanium dioxide nanoparticle on the redox regulatory network of cells
Author(s)
Khanal, Dipesh
Advisor(s)
Payne, Christine K.
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Abstract
The extensive industrial and commercial use of titanium dioxide nanoparticles (TiO2 NPs) in paints, cosmetics, and as food coloring additives is associated with high levels of TiO2 NPs released into the environment and subsequent human exposure. Previous studies have linked TiO2 NPs exposure to reactive oxygen species (ROS) production in cells; however, the exact mechanism between oxidative stress and cellular toxicity is unknown. We hypothesize that cellular binding and/or internalization of TiO2 NPs leads to a shift in transcriptional expression of oxidative stress related genes. As a first step, we investigated the size distribution of TiO2 NPs in different biologically relevant media. Our results show that TiO2 NPs agglomerate into large particles, and are comparatively smaller in human serum (200-700 nm) than in water (800-1500 nm). The formation of a protein corona, verified by gel electrophoresis, contributes to decreased aggregation in human serum. TiO2 NPs exposure to the cells, followed by reverse transcriptase polymerase chain reaction (qPCR) analysis of oxidative stress related genes (in collaboration with Prof. Melissa Kemp, BME) has led to the identification of the genes with altered expression. Specifically, peroxiredoxin 1 and peroxiredoxin 5 showed up regulation, whereas peroxiredoxin 3 and peroxiredoxin 4 showed down regulation. This approach of probing the redox response of cells in terms of collective gene expression, rather than focusing on a single pathway, will provide a whole cell mechanistic model of nanoparticle-induced oxidative stress.
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2015-04-27
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