Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Apopa, Patrick L.; Qian, Y; Shao, Rong; Guo, Nancy Lan; Schwegler‐Berry, Diane; Pacurari, Maricica; Porter, Dale W.; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent; Flynn, Daniel C.

doi:10.1186/1743-8977-6-1

Cited by 294 publications

(231 citation statements)

References 37 publications

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“…The canonical perpetrator of NM-induced toxicity is oxidative stress 6 . Metal oxide NM, like ZnO and CuO, can induce elevation of intracellular reactive oxygen species (ROS) 6 , which indirectly cause ECL through cytoskeletal damage 8 or indirectly by activating apoptotic events, resulting in cellular shrinkage. Therefore, initially we checked whether TiO 2 -NM-induced ROS generation may have caused ECL.…”

Section: Resultsmentioning

confidence: 99%

“…Species like vascular endothelial growth factor (VEGF), thrombin, angiopoietin-like 4 protein 4 and histamine 5 can perturb this tightly regulated intercellular and intracellular homeostasis and result in ECL. Toxic metal oxide NM are known to be endocytosed and induced oxidative stress 6,7 ; indirectly leading to ECL 8 . However, we postulate a novel mechanism where ECL can occur without uptake of NM but by virtue of their small dimensions, NM can migrate into and disrupt the adherens junction between endothelial cells.…”

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confidence: 99%

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Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO 2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO 2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as b-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO 2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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“…73 In human microvascular endothelial cells, iron NPs were shown to enhance cell permeability through the production of ROS and stabilization of microtubules. 74 Several studies have demonstrated that NP-mediated ROS can induce or mediate the activation of the Mitogen-activated protein kinase (MAPK) pathways ( Fig. 3).…”

Section: The Role Of Oxidative Stress and Ros In Np Induced Signalingmentioning

confidence: 99%

Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles

Rauch¹,

Kölch²,

et al. 2013

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Introduction 3391 2. Medical Applications of Nanomaterials 3391 2.1. Use of Nanomaterials in Diagnostic Applications 3392 3. Interaction of Nanomaterials with Living Cells 3392 3.1. Role of Physicochemical NP Properties in the Interaction between NPs and Biological Systems 3393 3.2. NP Uptake into the Cells 3393 3.2.1. Role of Size and Shape in NP Uptake 3393 3.2.2. Role of Surface Charge and Protein Corona on NP Uptake 3395 3.3. Activation of Signal Processing Pathways by NPs 3397 3.3.1. Interaction of NPs with Cell Membrane Receptors 3397 3.3.2. Role of Oxidative Stress and ROS in NP-Induced Signaling 3398 3.3.3. NPs Induce Cell Death Pathways 3400 3.3.4. Activation of Mechanotransduction Receptors by Magnetic NPs 3400 4. Magnetic NPs and Cell Signaling 3400 4.1. Controlled Activation of Cell Surface Receptors by Magnetic NPs 3400 4.1.1. Activation of Signal Transduction Receptors by Magnetic NPs 3400 4.1.2. Activation of Mechanotransduction Receptors and Mechanosensitive Signaling Pathways by Magnetic NPs 3400 4.2. Pathway Activation by Magnetic-NP-Induced Hyperthermia 3401 4.2.1. Molecular Targets of Hyperthermia: Heat Shock Proteins and p53 3401 5. Conclusions 3402 Author Information 3402 Corresponding Author 3402 Present Address 3402 Notes 3402 Biographies 3402 Acknowledgments 3403 References 3403

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“…Human health is shown to be affected more by enhanced exposure levels to cumulative PM (mainly associated with pulmonary diseases) or their chemical composition (Donaldson and Seaton, 2012;Warheit et al, 2007) than by single events of acute pollutant concentration (Kariisa et al, 2014). For instance, exacerbated exposure to iron (Fe) particles has been suggested to directly affect human cell permeability (Apopa et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Characterization of leaf-level particulate matter for an industrial city using electron microscopy and X-ray microanalysis

Sgrigna

Baldacchini

Esposito

et al. 2016

Science of The Total Environment

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This study reports application of monitoring and characterization protocol for particulate matter (PM) deposited on tree leaves, using Quercus ilex as a case study species. The study area is located in the industrial city of Terni in central Italy, with high PM concentrations. Four trees were selected as representative of distinct pollution environments based on their proximity to a steel factory and a street. Wash off from leaves onto cellulose filters were characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy, inferring the associations between particle sizes, chemical composition, and sampling location.Modeling of particle size distributions showed a tri-modal fingerprint, with the three modes centered at 0.6 (factory related), 1.2 (urban background), and 2.6 μm (traffic related). Chemical detection identified 23 elements abundant in the PM samples. Principal component analysis recognized iron and copper as sourcespecific PM markers, attributed mainly to industrial and heavy traffic pollution respectively. Upscaling these results on leaf area basis provided a useful indicator for strategic evaluation of harmful PM pollutants using tree leaves.

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Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Cited by 294 publications

References 37 publications

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles

Characterization of leaf-level particulate matter for an industrial city using electron microscopy and X-ray microanalysis

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