scholarly journals Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

2016 ◽  
Vol 134 ◽  
pp. 163-173 ◽  
Author(s):  
Lucie Armand ◽  
Mathilde Biola-Clier ◽  
Laure Bobyk ◽  
Véronique Collin-Faure ◽  
Hélène Diemer ◽  
...  
Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 185 ◽  
Author(s):  
Mathilde Biola-Clier ◽  
Jean-Charles Gaillard ◽  
Thierry Rabilloud ◽  
Jean Armengaud ◽  
Marie Carriere

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.


2017 ◽  
Vol 276 ◽  
pp. 48-61 ◽  
Author(s):  
Andrea Stoccoro ◽  
Sebastiano Di Bucchianico ◽  
Fabio Coppedè ◽  
Jessica Ponti ◽  
Chiara Uboldi ◽  
...  

Mutagenesis ◽  
2016 ◽  
Vol 32 (1) ◽  
pp. 161-172 ◽  
Author(s):  
M. Biola-Clier ◽  
D. Beal ◽  
S. Caillat ◽  
S. Libert ◽  
L. Armand ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Francesca Mancuso ◽  
Iva Arato ◽  
Alessandro Di Michele ◽  
Cinzia Antognelli ◽  
Luca Angelini ◽  
...  

The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. Titanium dioxide nanoparticles (TiO2 NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO2 NPs induced reproductive toxicity in male animals. In this in vitro study, porcine prepubertal Sertoli cells (SCs) have undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposures at both subtoxic (5 µg/ml) and toxic (100 µg/ml) doses of TiO2 NPs. After performing synthesis and characterization of nanoparticles, we focused on SCs morphological/ultrastructural analysis, apoptosis, and functionality (AMH, inhibin B), ROS production and oxidative DNA damage, gene expression of antioxidant enzymes, proinflammatory/immunomodulatory cytokines, and MAPK kinase signaling pathway. We found that 5 µg/ml TiO2 NPs did not induce substantial morphological changes overtime, but ultrastructural alterations appeared at the third week. Conversely, SCs exposed to 100 µg/ml TiO2 NPs throughout the whole experiment showed morphological and ultrastructural modifications. TiO2 NPs exposure, at each concentration, induced the activation of caspase-3 at the first and second week. AMH and inhibin B gene expression significantly decreased up to the third week at both concentrations of nanoparticles. The toxic dose of TiO2 NPs induced a marked increase of intracellular ROS and DNA damage at all exposure times. At both concentrations, the increased gene expression of antioxidant enzymes such as SOD and HO-1 was observed whereas, at the toxic dose, a clear proinflammatory stress was evaluated along with the steady increase in the gene expression of IL-1α and IL-6. At both concentrations, an increased phosphorylation ratio of p-ERK1/2 was observed up to the second week followed by the increased phosphorylation ratio of p-NF-kB in the chronic exposure. Although in vitro, this pilot study highlights the adverse effects even of subtoxic dose of TiO2 NPs on porcine prepubertal SCs functionality and viability and, more importantly, set the basis for further in vivo studies, especially in chronic exposure at subtoxic dose of TiO2 NPs, a condition closer to the human exposure to this nanoagent.


1997 ◽  
Vol 3 (S2) ◽  
pp. 925-926
Author(s):  
R.C. Stearns ◽  
J.J. Godleski

Although alveolar macrophages are the primary defensive cells of the lung against invading bacteria and foreign particles, recent studies suggest that particle uptake and translocation is a role common to alveolar epithelium (reviewed by Churg). The purpose of this investigation is to define the phagocytic capabilities of human A549 cell line using 50 nm inert Titanium Dioxide, (TiO2), particles.A549 cells at 0.5×l06cells/ml, in F12 Kaighn’s modification medium (F12K) with 10% heat-inactivated fetal bovine serum, l00U/ml penicillin and lOOng/ml streptomycin were cultured on alcar discs in 24-well plates, incubated at 37°C, 5% CO2 in a humidified incubator for 4 days. The cells were then exposed to TiO2 particles (final concentration 4Oμg/ml) in serum-free F12K media for 24 h. After 24h, the cells were fixed in 2.5% glutaraldehyde in 0.1 M potassium phosphate buffer overnight. The cells were post-fixed with 1% OSO4, dehydrated in series of ethanol and propylene oxide, infiltrated and embedded with araldite 502.


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