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Tungsten Carbide-Cobalt Nanoparticles Induce Reactive Oxygen Species, AKT, ERK, AP-1, NF-κB, VEGF, and Angiogenesis

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Abstract

Powder mixtures of tungsten carbide and metallic cobalt (WC-Co) are widely used in various products. Nanoparticles are engineered structures with at least one dimension of 100 nm or smaller. WC-Co is known to be associated with lung injury and diseases. Angiogenesis is a key process during vasculature, carcinogenesis, recovery of injury, and inflammatory diseases. However, the cellular effects of WC-Co nanoparticles on angiogenesis remain to be elucidated. In this study, we investigated angiogenic response and relative mechanisms after exposure to WC-Co nanoparticles. Our results showed that WC-Co nanoparticles at 5 μg/cm2 induced ROS production which activated AKT and ERK1/2 signaling pathways in lung epithelial cells by reactive oxygen species (ROS) staining and immunoblotting; WC-Co treatment also increased transcriptional activation of AP-1, NF-κB, and VEGF by reporter assay. Further studies demonstrated that ROS are upstream molecules of AKT and ERK signaling pathways; the activation of AP-1, NF-κB, and VEGF was through ROS generation, AKT and ERK1/2 activation. In addition, WC-Co nanoparticles affected the cells to induce angiogenesis by chicken chorioallantoic membrane (CAM) assay. These results illustrate that exposure to WC-Co nanoparticles induces angiogenic response by activating ROS, AKT, and ERK1/2 signaling pathways and the downstream molecules and elucidate the potential molecular mechanisms during this process. This information may be useful for preventing potential damage from nanoparticle exposure in the future.

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Abbreviations

WC-Co:

Tungsten carbide and metallic cobalt

ROS:

Reactive oxygen species

CAM:

Chicken chorioallantoic membrane

PBS:

Phosphate-buffered saline

DCFH-DA:

2′,7′-Dichlorofluorescein diacetate

H2O2 :

Hydrogen peroxide

AP-1:

Activator protein-1

NF-κB:

Nuclear factor kappa B

VEGF:

Vascular endothelial growth factor

ERK:

Extracellular signal regulated kinase

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Acknowledgments

This work was supported by R01HL091456, R01ES020868, and R21CA175975 from National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA

    Ling-Zhi Liu, Yingxue Zhu, Bruce A. Fenderson & Bing-Hua Jiang

  2. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA

    Min Ding

  3. Mary Babb Randolph Cancer Center, Department of Biochemistry, West Virginia University, Morgantown, WV, USA

    Jenny Z. Zheng & Jing J. Yu

  4. Department of Orthopedics, West Virginia University, Morgantown, WV, USA

    Bingyun Li

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  1. Ling-Zhi Liu
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Correspondence to Ling-Zhi Liu or Bing-Hua Jiang.

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Liu, LZ., Ding, M., Zheng, J.Z. et al. Tungsten Carbide-Cobalt Nanoparticles Induce Reactive Oxygen Species, AKT, ERK, AP-1, NF-κB, VEGF, and Angiogenesis. Biol Trace Elem Res 166, 57–65 (2015). https://doi.org/10.1007/s12011-015-0331-6

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