title: Copper Oxide Nanoparticles Reduce Vasculogenesis in Transgenic Zebrafish Through Down-Regulation of Vascular Endothelial Growth Factor Expression and Induction of Apoptosis.
abstract: The present study investigated the effects of exposure to metal oxide nanoparticles on vasculogenesis/angiogenesis using transgenic zebrafish. The study also examined the potential mechanisms involved in those effects using human umbilical vein endothelial cells (HUVEC). TG (nacre/fli1:EGFP) zebrafish were exposed to nano-sized titanium dioxide (TiO2), silica dioxide (SiO2), and copper oxide (CuO) particles at 0.01, 1 and 100 µg/ml concentrations from 1 to 5 dpf (day-post-fertilization). Angiogenesis was evaluated morphologically at the end of exposure. Exposure to CuO nanoparticles reduced the number of transversely-running subintestinal vessels in TG zebrafish. Exposure to CuO nanoparticles down-regulated the expression of vascular endothelial growth factor (VEGF) and VEGF receptor in endothelial cells sorted by Fluorescence Activated Cell Sorter (FACS). Exposure of HUVEC to CuO nanoparticles reduced cell viability and increased apoptotic index in a dose-dependent manner. The results suggested that CuO nanoparticles inhibit vasculogenesis through reduction of VEGF expression and induction of apoptosis.
authors.forename: Jie
authors.initials: J
authors.lastname: Chang
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimada
authors.forename: Saeko
authors.initials: S
authors.lastname: Tada-Oikawa
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroyanagi
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhang
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Radwa
authors.initials: R
authors.lastname: Sehsah
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D015027:Zebrafish
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003300:Copper; C000520:cuprous oxide