PMID- 23958343
OWN - NLM
STAT- MEDLINE
DCOM- 20140422
LR  - 20181202
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1534
DP  - 2013 Oct 9
TI  - Novel effects of edaravone on human brain microvascular endothelial cells 
      revealed by a proteomic approach.
PG  - 87-94
LID - S0006-8993(13)01122-0 [pii]
LID - 10.1016/j.brainres.2013.08.019 [doi]
AB  - 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)-1beta-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.
CI  - (c) 2013 Elsevier B.V. All rights reserved.
FAU - Onodera, Hidetaka
AU  - Onodera H
AD  - 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.
FAU - Arito, Mitsumi
AU  - Arito M
FAU - Sato, Toshiyuki
AU  - Sato T
FAU - Ito, Hidemichi
AU  - Ito H
FAU - Hashimoto, Takuo
AU  - Hashimoto T
FAU - Tanaka, Yuichiro
AU  - Tanaka Y
FAU - Kurokawa, Manae S
AU  - Kurokawa MS
FAU - Okamoto, Kazuki
AU  - Okamoto K
FAU - Suematsu, Naoya
AU  - Suematsu N
FAU - Kato, Tomohiro
AU  - Kato T
LA  - eng
PT  - Journal Article
DEP - 20130816
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 33X04XA5AT (Lactic Acid)
RN  - S798V6YJRP (Edaravone)
RN  - T3CHA1B51H (Antipyrine)
SB  - IM
MH  - Antipyrine/*analogs & derivatives/pharmacology
MH  - Brain/blood supply/*drug effects/metabolism
MH  - Cells, Cultured
MH  - Edaravone
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Lactic Acid/metabolism
MH  - Microvessels/drug effects
MH  - *Proteomics
MH  - Tight Junctions/drug effects/metabolism
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Edaravone
OT  - Endothelium
OT  - Pharmacology
EDAT- 2013/08/21 06:00
MHDA- 2014/04/23 06:00
CRDT- 2013/08/21 06:00
PHST- 2013/07/19 00:00 [received]
PHST- 2013/08/09 00:00 [accepted]
PHST- 2013/08/21 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/04/23 06:00 [medline]
AID - S0006-8993(13)01122-0 [pii]
AID - 10.1016/j.brainres.2013.08.019 [doi]
PST - ppublish
SO  - Brain Res. 2013 Oct 9;1534:87-94. doi: 10.1016/j.brainres.2013.08.019. Epub 2013 
      Aug 16.