title: Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach.
abstract: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger used for acute ischemic stroke. However, it is not known whether edaravone works only as a free radical scavenger or possess other pharmacological actions. Therefore, we elucidated the effects of edaravone on human brain microvascular endothelial cells (HBMECs) by 2 dimensional fluorescence difference gel electrophoresis (2D-DIGE). We found 38 protein spots the intensity of which was significantly altered 1.3 fold on average (p< 0.05) by the edaravone treatment and successfully identified 17 proteins of those. Four of those 17 proteins were cytoskeleton proteins or cytoskeleton-regulating proteins. Therefore, we subsequently investigated the change of size and shape of the cells, the actin network, and the tight junction of HBMEC by immunocytochemistry. As a result, most edaravone-treated HBMECs became larger and rounder compared with those that were not treated. Furthermore, edaravone-treated HBMECs formed gathering zona occludens (ZO)-1, a tight junction protein, along the junction of the cells. In addition, we found that edaravone suppressed interleukin (IL)-1β-induced secretion of monocyte chemoattractant protein-1 (MCP-1), which was reported to increase cell permeability. We found a novel function of edaravone is the promotion of tight junction formations of vascular endothelial cells partly via the down-regulation of MCP-1 secretion. These data provide fundamental and useful information in the clinical use of edaravone in patients with cerebral vascular diseases.
authors: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8512, Japan; Department of Neurosurgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8512, Japan.
authors: Hidetaka
authors: H
authors: Onodera
authors: Mitsumi
authors: M
authors: Arito
authors: Toshiyuki
authors: T
authors: Sato
authors: Hidemichi
authors: H
authors: Ito
authors: Takuo
authors: T
authors: Hashimoto
authors: Yuichiro
authors: Y
authors: Tanaka
authors: Manae S
authors: MS
authors: Kurokawa
authors: Kazuki
authors: K
authors: Okamoto
authors: Naoya
authors: N
authors: Suematsu
authors: Tomohiro
authors: T
authors: Kato
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D000077553:Edaravone; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects; D040901:Proteomics; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D019344:Lactic Acid; D000077553:Edaravone; D000983:Antipyrine
keywords: Blood–brain barrier; Edaravone; Endothelium; Pharmacology