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Differential genomic effects on signaling pathways by two different CeO2 nanoparticles in HepG2 cells
Citation:
Thai, S., K. Wallace, C. Jones, H. Ren, B. Castellon, J. Crooks, E. Grulke, AND K. Kitchin. Differential genomic effects on signaling pathways by two different CeO2 nanoparticles in HepG2 cells. Journal of Nanoscience and Nanotechnology. American Scientific Publishers , VALENCIA, CA, 15(12):9925-37, (2015).
Impact/Purpose:
Thus, the purpose of the studies reported here is to contribute a data set to better connect physical-chemical properties with biological and toxicological effects.
Description:
To investigate genomic effects, human liver hepatocellular carcinoma (HepG2) cells were exposed for three days to two different forms of nanoparticles both composed of Ce02 (0.3, 3 and 30 µg/mL). The two Ce02 nanopartices had dry primary particle sizes of 8 nanometers {(M) made by NanoAmor} and 58 nanometers {(L) made by Alfa Aesar} and differ in various other physical-chemical properties as well. The smaller particle has stronger antioxidant properties, probably because it has higher Ce3+ levels on the particle surface, as well as more surface area per unit weight. Nanoparticle M showed a normal dose-response pattern wth 363, 633 and 1273 differentially expressed genes (DEGs) at 0.3, 3 and 30 µg/ml, respectively. In contrast, nanoparticle L showed a puzzling dose-response pattern with the most DEGs found in the lowest exposure group with 1049, 303 and 323 DEGs at 0.3, 3 and 30 µg/mL, respectively. This systems biological genomic study showed that the major altered pathways by these two nano cerium oxides were protein synthesis, stress response, proliferation/cell cycle, cytoskeleton remodeling/actin polymerization and cellular metabolism. Some of the canonical pathways affected were mTOR signaling, EIF2 signaling, fatty acid activation, G2/M DNA damage checkpoint regulation, glycolysis and protein ubquitination. These two Ce02 nanoparticles differed considerably in their genomic effects. M is more active than L in respect to altering the pathways of mitochondrial dysfunction, acute phase response, apoptosis, 14-3-3 mediated signaling, remodeling of epithelial adherens junction signaling, actin nucleation by ARP-WASP complex, altered TCA cycle and elevated fatty acid concentrations by metabolomics. However, L is more active than M in respect to the pathways of NRF2-mediated stress response and hepatc fibrosis/hepatic stellate cell activation. One major difference in the cell response to nano M and L is that nano M caused the Warburg effect while nano L dd not.
