Dataset Information

Effects of titanium dioxide (TiO2) nanoparticles (NPs) on endothelial cells

ABSTRACT: The widespread commercial use of TiO2-NPs, such as in medical stents, has led to extensive investigations on their toxicity and biological impact but lacks a detailed study on their effects. Proteomics and transcriptomics are key methodologies to unravel cellular dynamics, macromolecular interactions and biological response to NP exposure through the protein or gene identification and quantification. We focus on integration of several Omics strategies that could offer a more complex understanding of the impact. In this study, our goal was to gain insight into the cellular response after the exposure to sublethal concentration of TiO2-ultra small nanoparticles (USNPs) and NPs by analyzing the modification on the genomic and proteomic expression in human microdermal endothelial cells (HMEC-1). We investigated the correlation between the NP size and the cellular response to the exposure. We evaluated if multiOmics approaches could thus reveal more extensive information on the potential cellular responses to NPs exposure.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Endometrial Microvascular Endothelial Cells, Cell Culture

DISEASE(S): Disease Free,Mixed Disorder As Reaction To Stress

SUBMITTER: Jacob Kuruvilla

LAB HEAD: Susana Cristobal

PROVIDER: PXD005359 | Pride | 2019-01-16

REPOSITORIES: Pride

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Publications

Proteomic Analysis of Endothelial Cells Exposed to Ultrasmall Nanoparticles Reveals Disruption in Paracellular and Transcellular Transport.

Kuruvilla Jacob J Bayat Narges N Cristobal Susana S

Proteomics 20190225 5

The large interactive surfaces of nanoparticles (NPs) increase the opportunities to develop NPs for vascular targeting. Proteomic analysis of endothelial cells exposed to NPs reveals the cellular response and turns the focus into the impairment of the endothelial permeability. Here, quantitative proteomics and transcriptome sequencing are combined to evaluate the effects of exposure to sub-lethal concentrations of TiO<sub>2</sub> -USNPs and TiO<sub>2</sub> -NPs on human dermal microvascular endo ...[more]

PMID: 30632670

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Project description:An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. An estimated 1% or less of the nanoparticles (NPs) deposited in lungs translocate to systemic circulation and enter other organs; however this estimation may not be accurate considering the low sensitivity of the existing in vivo NP detection methods. Moreover, the biological outcomes of such low levels of translocation are not elucidated. The objectives of the present study were to employ a Nano-scale Hyperspectral Microscope to spatially observe and spectrally profile NPs in tissues, and characterize the effects of NPs in blood, liver and heart following pulmonary deposition and subsequent translocation from lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 and 162 µg per mouse of industrially relevant non-doped titanium dioxide nanoparticles (nano-TiO2). Using the Nano-scale Hyperspectral Microscope translocation to heart and liver was confirmed at both doses and to blood at the highest dose at 24 hours post-exposure time-point. The analysis of biological effects using DNA microarrays, RT-qPCR and ELISA revealed activation of complement cascade and inflammatory process in heart and specific activation of complement factor 3 in blood, potentially suggestive of activation of early innate immune response essential for particle opsonisation and clearance. The liver showed subtle response with changes in the expression of few genes associated with acute phase genes. This study establishes a direct link between particle translocation and systemic effects. This experiment consists of one dose of nano-TiO2 (162 ug) and one control. There are 2 time points for each treatment and control group, e.g., day 1 and day 28. Each dose or time point has 5-6 biological replicates. There are total 22 samples (arrays)

Dataset Information

Effects of titanium dioxide (TiO2) nanoparticles (NPs) on endothelial cells

Publications

Proteomic Analysis of Endothelial Cells Exposed to Ultrasmall Nanoparticles Reveals Disruption in Paracellular and Transcellular Transport.

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