title: Silver nanoparticles interact with the cell membrane and increase endothelial permeability by promoting VE-cadherin internalization.
abstract: The toxicological risks of silver nanoparticles (AgNPs) have attracted widespread attention, and many studies have been published that have contributed to understanding AgNPs-induced toxicity. However, little attention has been paid to the low-dose effects of AgNPs and the related toxicological mechanism is still unclear. Here, we show that short-term exposure to AgNPs at low doses induces a substantial increase in human umbilical vein endothelial cells (HUVECs) monolayer permeability, whereas Ag ions at low doses do not induce an observable increase in monolayer permeability. This effect is independent of oxidative stress and apoptosis. Scanning electron microscopy confirms that AgNPs adhere to the cell membrane after 1h exposure. Furthermore, adhesion of AgNPs to the cell membrane can trigger vascular endothelial (VE)-cadherin phosphorylation at Y658 followed by VE-cadherin internalization, which lead to the increase in endothelial monolayer permeability. Our data show that surface interactions of AgNPs with the cell membrane, in other words, the particle effect, is a major factor leading to endothelial dysfunction following low-dose and short-term exposure. Our findings will contribute to understanding the health effects and the toxicological mechanisms of AgNPs.
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Jimei Road 1799, Xiamen 361021, China. Electronic address: hwzhang@iue.ac.cn.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D012834:Silver / Q000737:chemistry / Q000633:toxicity*
chemical_list: D015820:Cadherins; D012834:Silver
keywords: Endothelium; Phosphorylation; Silver nanoparticles; Surface interaction; VE-cadherin