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

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/cm(2) 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.