Citation:

Thai, S., C. Jones, B. Robinette, H. Ren, B. Vallanat, A. Astriab Fisher, AND K. Kitchin. Differential genomic effects of four nano-sized and one micro-sized CeO2 particles on HepG2 cells. Materials Express. American Scientific Publishers , VALENCIA, CA, 13(10):1799-1811, (2023). https://doi.org/10.1166/mex.2023.2527

Impact/Purpose:

Increasing evidence suggesting the special physiological properties of nanoparticles pose potential health risk to human. In previously published journal articles, we reported metabolomics study of four nano-sized and one micrometer-sized cerium oxide (CeO2) particles. CeO2 nano- and micrometer-sized particles induced fatty acid accumulations in HepG2 cells.  The purpose of this genomic study is to study the genomic changes that induced by these CeO2 particle.  We report in this study  that there were gene expression changes that correlated with the induced fatty acid accumulations.  However, one nanoparticle (X5) did not show these gene expression changes, even though it induced fatty acid accumulation. Possible mechanism were proposed for X5 induced fatty acid accumulations.

Description:

The objective of this research was to perform a genomics study of five cerium oxide particles, 4 nano and one micrometer-sized particles which have been studied previously by our group with respect to cytotoxicity, biochemistry and metabolomics. Human liver carcinoma HepG2 cells were exposed to between 0.3 to 300 ug/ml of CeO2 particles for 72 hours and then total RNA was harvested. Fatty acid accumulations were observed with W4, X5, Z7 and less with Q but not Y6. The gene expression changes in the fatty acid metabolism genes correlated the fatty acid accumulations we detected in the prior metabolomics study for the CeO2 particles named W4, Y6, Z7 and Q, but not for X5. In particular, the observed genomics effects on fatty acid uptake and fatty acid oxidation offer a possible explanation of why many CeO2 particles increase cellular free fatty acid concentrations in HepG2 cells.  The major genomic changes observed in this study were sirtuin, ubiquitination signaling pathways, NRF2-mediated stress response and mitochondrial dysfunction. The sirtuin pathway was affected by many CeO2 particle treatments.  Sirtuin signaling itself is sensitive to oxidative stress state of the cells and may be an important contributor in CeO2 particle induced fatty acid accumulation. Ubiquitination pathway regulates many protein functions in the cells, including sirtuin signaling, NRF2 mediated stress, and mitochondrial dysfunction pathways.  NRF2-mediated stress response and mitochondrial were reported to be altered in many nanoparticles treated cells. All these pathways may contribute to the fatty acid accumulation in the CeO2 particles treated cells.

URLs/Downloads:

Record Details: