title: 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.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA, ling-zhi.liu@jefferson.edu.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Jenny Z
authors.initials: JZ
authors.lastname: Zheng
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Fenderson
authors.forename: Bingyun
authors.initials: B
authors.lastname: Li
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Yu
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D017973:Tungsten Compounds / Q000737:chemistry / Q000633:toxicity*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D017973:Tungsten Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C002802:tungsten carbide; D003035:Cobalt; D008156:Luciferases; D051057:Proto-Oncogene Proteins c-akt