Cell cycle synchronization reveals greater G2/M-phase accumulation of lung epithelial cells exposed to titanium dioxide nanoparticles

Medina‐Reyes, Estefany I.; Bucio-López, Laura; Freyre-Fonseca, Verónica; Sánchez-Pérez, Yesennia; García-Cuéllar, Claudia M.; Morales‐Bárcenas, Rocío; Pedraza‐Chaverrí, José; Chirino, Yolanda I.

doi:10.1007/s11356-014-3871-y

Cited by 14 publications

(11 citation statements)

References 25 publications

(25 reference statements)

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“…This alteration would result from modulation of the phosphorylation of these proteins. Moreover, some of these proteins play roles in the DNA damage response, which is activated in TiO 2 -NP-exposed cells, particularly via impairment of the DNA repair as previously demonstrated in A549 cells exposed to the same TiO 2 -NPs and in the same conditions as in the present study [13,14] and via modulation of cell cycle progression [15][16][17][18][19][20]. This is the case of BAG6, which is involved in DNA-damage induced apoptosis by binding EP300, itself involved in the regulation of TP53 transcriptional activity [56].…”

Section: Protein Ontologysupporting

confidence: 71%

“…Impaired cell cycle progression induced by TiO 2 -NPs is generally reported as cell accumulation in S or G2-M phases [15][16][17][18][19][20]. It is concomitant with impairment of mitotic progression, formation of multipolar mitotic spindles, abnormal chromosome segregation during anaphase and telophase, with deregulation of the function of PLK1 kinase [12].…”

Section: Protein Ontologymentioning

confidence: 99%

“…TiO 2 also causes oxidative damage to DNA without accumulating inside cell nucleus, except if the cell has undergone mitosis, one of the stages of which is the rupture of the nuclear envelope [11]. This genotoxicity is concomitant to impairment of the mitotic spindle assembly and function [12], decreased DNA repair activities [13,14] and cell cycle progression [15][16][17][18][19][20], suggesting that TiO 2 -NPs exert indirect primary genotoxicity [11]. Finally, TiO 2 -NPs have been shown to affect the autophagic process [21,22], and this property has been proposed as a possible therapeutic approach to treat cancer [23].…”

Section: Introductionmentioning

confidence: 99%

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Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells

et al. 2020

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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.

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Section: Protein Ontologysupporting

confidence: 71%

Section: Protein Ontologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells

et al. 2020

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“…These contradictory conclusions may be due to the varying experimental conditions, to the different cellular models and culture media, and to the different sizes of TiO2 NPs. Moreover, synchronization was suggested to reveal alterations in cell cycle distribution that could be hidden in unsynchronized cell cultures [22]. Additionally, these discrepancies may also be ascribed to the metal NP interferences with fluorescent probes used in flow cytometric analysis of DNA [23].…”

Section: Introductionmentioning

confidence: 99%

Effects of TiO2 and Co3O4 Nanoparticles on Cell Cycle of a Pulmonary Cell Line (A549)

Pinelli¹,

Poli²,

Alinovi³

et al. 2018

Preprint

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The wide range of applications of nanoparticles (NPs) has increased the probability of environmental and occupational exposure. In a previous comparative study on cell line A549, we observed that oxidative stress caused by Co3O4 NPs affects the energetic homeostasis and the detoxification capacity, preventing autophagy induced by TiO2 NPs. In this study, we have investigated the effects of NPs on the cell cycle.Cytofluorimetric analysis showed a slow-down of the cell cycle progression for both NPs, with increases in the percentage of resting cells in the G0/G1. These observations were confirmed by a reduced expression of all cyclins, especially of CCNE1 and CDK2, involved in the late stages of the G1 phase, coupled with a significant increase in the expression of p21 only for Co3O4 NP exposure. On the contrary, the effects of TiO2 NPs were modest. Cell cycle related miRNA-34a, miRNA-126 and miRNA-1290 resulted increased at different early time-points (4-8h) but were down-expressed at 24h-48h only after TiO2 NP exposure. Our results show that NPs have an antiproliferative effect and deregulate cell cycle on A549 cells. These effects should not be underestimated because regulation of cycle progression is crucial for cell survival and repair of genetic damage.

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“…The main administration routes in in vivo studies included inhalation [14], intratracheal [15] or nasal instillation [16], oral gavage and dermal exposure [17], intragastric feeding [18], intraperitoneal [19], and intravenous injection [15]. Numerous reports have revealed that when the TiO 2 NPs were administrated and transported into second targets, they could induce renal fibrosis, change cell cycle of lung epithelial cell, disturb the metabolism of hepatocytes, and impair the spleen [20][21][22][23]. The central nervous system (CNS), including the brain and spinal cord, is an extremely important system for human beings.…”

Section: Introductionmentioning

confidence: 99%

A review on potential neurotoxicity of titanium dioxide nanoparticles

Song¹,

Liu²,

Feng³

et al. 2016

Nano Online

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As the rapid development of nanotechnology in the past three decades, titanium dioxide nanoparticles (TiO 2 NPs), for their peculiar physicochemical properties, are widely applied in consumer products, food additives, cosmetics, drug carriers, and so on. However, little is known about their potential exposure and neurotoxic effects. Once NPs are unintentionally exposed to human beings, they could be absorbed, and then accumulated in the brain regions by passing through the blood-brain barrier (BBB) or through the nose-to-brain pathway, potentially leading to dysfunctions of central nerve system (CNS). Besides, NPs may affect the brain development of embryo by crossing the placental barrier. A few in vivo and in vitro researches have demonstrated that the morphology and function of neuronal or glial cells could be impaired by TiO 2 NPs which might induce cell necrosis. Cellular components, such as mitochondrial, lysosome, and cytoskeleton, could also be influenced as well. The recognition ability, spatial memory, and learning ability of TiO 2 NPs-treated rodents were significantly impaired, which meant that accumulation of TiO 2 NPs in the brain could lead to neurodegeneration. However, conclusions obtained from those studies were not consistent with each other as researchers may choose different experimental parameters, including administration ways, dosage, size, and crystal structure of TiO 2 NPs. Therefore, in order to fully understand the potential risks of TiO 2 NPs to brain health, figure out research areas where further studies are required, and improve its bio-safety for applications in the near future, how TiO 2 NPs interact with the brain is investigated in this review by summarizing the current researches on neurotoxicity induced by TiO 2 NPs.International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Cell cycle synchronization reveals greater G2/M-phase accumulation of lung epithelial cells exposed to titanium dioxide nanoparticles

Cited by 14 publications

References 25 publications

Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells

Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells

Effects of TiO<sub>2</sub> and Co<sub>3</sub>O<sub>4 </sub>Nanoparticles on Cell Cycle of a Pulmonary Cell Line (A549)

A review on potential neurotoxicity of titanium dioxide nanoparticles

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