Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells

Abstract

TiO2 nanoparticles (NPs) are one of the most produced NPs worldwide and are used in many consumer products. Their impact on human health, especially through inhalation, has been studied for more than two decades. TiO2 is known for its strong affinity towards phosphates, and consequently interaction with cellular phosphates may be one of the mechanisms driving its toxicity. In the present study, we used a phosphoproteomics approach to document the interaction of TiO2-NP with phosphoproteins from A549 human pulmonary alveolar epithelial cells. Cells were exposed to 21 nm anatase/rutile TiO2-NPs, then their phosphopeptides were extracted and analyzed using shotgun proteomics. By comparing the phosphoprotein content, phosphorylation status and phosphorylation sites of exposed cells with that of control cells, our results show that by affecting the phosphoproteome, TiO2-NPs affect cellular processes such as apoptosis, linked with cell cycle and the DNA damage response, TP53 being central to these pathways. Other pathways including inflammation and molecular transport are also affected. These molecular mechanisms of TiO2-NP toxicity have been reported previously, our study shows for the first time that they may derive from phosphoproteome modulation, which could be one of their upstream regulators.

Toxicological Consequences of Titanium Dioxide Nanoparticles (TiO2NPs) and Their Jeopardy to Human Population

“…Previous in vitro and in vivo tests have confirmed the toxic effects of TiO 2 NPs on the human body like altered cell cycle, nuclear stenosis, and apoptosis [ 26 – 29 ]. Studies have also shown that TiO 2 NPs causes DNA damage and causes rupturing of the small intestine epithelium, which is involved in the absorption of nutrients [ 30 ]. This damage is due to various ways, mainly by inhalation, injection, and skin contact, as well as digestion and absorption [ 11 ].…”

Analysis of Nanotoxicity with Integrated Omics and Mechanobiology

“…In addition, they elucidate the complexity of biological functions through statistical analyses and interpretations of bioinformatics. Recently, omics studies of NP-induced biological changes have been increasing in number [ 16 , 17 , 18 , 19 , 20 ]. Despite the high potential of targeting efficiency and the fascinating physicochemical properties of NPs, their adverse effects on cells, tissues, and organs remain a major challenge.…”

“…Recently, phosphoproteomics has been applied for the assessment of nanotoxicity. For example, Biola-Clier et al reported that analysis of the phosphoproteome in TiO 2 NP-treated A549 cells showed that the TiO 2 NPs altered cellular processes such as apoptosis, cell cycle and DNA damage response, autophagy progress, RNA dynamics, and intracellular transport [ 20 ]. In particular, TiO 2 NPs affected the phosphoproteome related to their upstream regulators.…”

Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation

“…NP-mediated toxicity is a rather complicated process and more factors, other than the ones we have determined, are at work. There have been numerous reports on titanium oxide [19], nanogold [20], carbon nanotubes [21], silica oxide [22], aluminum oxide [15], and cerium oxide [23] relating to cell killing. The final cell number that researchers observed was more than just the effect of cell death.…”