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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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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DOI: https://doi.org/10.1007/s12011-015-0331-6