title: Perfluorooctane sulfonate triggers tight junction "opening" in brain endothelial cells via phosphatidylinositol 3-kinase.
abstract: Perfluorooctane sulfonate (PFOS), an environmental pollutant, is widely distributed in humans and wildlife. Accumulation of PFOS in the brain and its neurotoxicity has been reported. Whether PFOS has any effect on the blood-brain barrier (BBB) remains unknown. In this study, human brain microvascular endothelial cells (HBMEC), which are the major components of BBB, were treated with PFOS and indicators of endothelial permeability were measured. Disassembly of endothelial tight junction (TJ) and increase of permeability were observed in response to PFOS. The PFOS-induced TJ disassembly in HBMEC was attenuated by pretreatment with PI3K inhibitors, whereas Rho kinase inhibitor had no such effect. Further results demonstrated that PFOS promoted the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling in HBMEC. We found that overexpression of PI3K dominant-negative mutant in HBMEC abolished the PFOS-induced TJ disassembly. These data demonstrated that PFOS can trigger the "opening" of tight junction in brain endothelial cells through PI3K signaling pathway.
authors.affiliation: Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Bei Er Road, Heping District, Shenyang 110001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhao
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: De-Shu
authors.initials: DS
authors.lastname: Shang
authors.forename: Wen-Gang
authors.initials: WG
authors.lastname: Fang
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D004785:Environmental Pollutants / Q000633:toxicity*; D004789:Enzyme Activation; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects*
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt