Intracellular Generation of Superoxide by TiO<sub>2</sub> Nanoparticles Decreases Histone Deacetylase 9 (HDAC9), an Epigenetic Modifier.

TitleIntracellular Generation of Superoxide by TiO2 Nanoparticles Decreases Histone Deacetylase 9 (HDAC9), an Epigenetic Modifier.
Publication TypeJournal Article
Year of Publication2020
AuthorsDT Jayaram, and CK Payne
JournalBioconjugate Chemistry
Volume31
Start Page1354
Issue5
Pagination1354 - 1361
Date Published05/2020
Abstract

Titanium dioxide (TiO<sub>2</sub>) nanoparticles are used on a massive scale in commercial and industrial products. Of specific concern is how the inhalation of these nanoparticles in a manufacturing setting may affect human health. We examine the cellular response to TiO<sub>2</sub> nanoparticles using a combination of cell-free spectroscopic assays, fluorescence microscopy, Western blotting, and TiO<sub>2</sub> nanoparticle surface modifications. These experiments show that TiO<sub>2</sub> nanoparticles generate superoxide, both in solution and in cells, and this intracellular superoxide decreases expression of histone deacetylase 9 (HDAC9), an epigenetic modifier. We use protein coronas formed from superoxide dismutase (SOD) and catalase, enzymes that scavenge reactive oxygen species (ROS), to probe the relationship between TiO<sub>2</sub> nanoparticles, ROS, and the subsequent cellular response. These protein coronas provide nanoparticle-localized scavengers that demonstrate that the nanoparticles are the source of the intracellular superoxide. Importantly, the use of a SOD corona or surface passivated TiO<sub>2</sub> nanoparticles prevents the decrease of HDAC9. These experiments elucidate the underlying mechanism of TiO<sub>2</sub> nanoparticle-mediated cellular responses including oxidative stress and changes in gene expression. They also provide the first demonstration of a protein corona as a tool for probing cellular responses to nanoparticles. Overall, this research shows that low, nontoxic concentrations of TiO<sub>2</sub> nanoparticles alter an enzyme responsible for epigenetic modifications, which points to concerns regarding long-term exposures in manufacturing settings.

DOI10.1021/acs.bioconjchem.0c00091
Short TitleBioconjugate Chemistry