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...
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| Veröffentlicht in: | Brain research 2013-10, Vol.1534, p.87-94 |
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| creator | Onodera, Hidetaka Arito, Mitsumi Sato, Toshiyuki Ito, Hidemichi Hashimoto, Takuo Tanaka, Yuichiro Kurokawa, Manae S Okamoto, Kazuki Suematsu, Naoya Kato, Tomohiro |
| description | 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. |
| doi_str_mv | 10.1016/j.brainres.2013.08.019 |
| format | Article |
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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.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2013.08.019</identifier><identifier>PMID: 23958343</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>actin ; Antipyrine - analogs & derivatives ; Antipyrine - pharmacology ; Biological and medical sciences ; Blood–brain barrier ; brain ; Brain - blood supply ; Brain - drug effects ; Brain - metabolism ; Cells, Cultured ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; chemokines ; cytoskeleton ; Edaravone ; endothelial cells ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Endothelium ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; fluorescence ; free radical scavengers ; Fundamental and applied biological sciences. Psychology ; gel electrophoresis ; HeLa Cells ; Humans ; immunocytochemistry ; interleukins ; Lactic Acid - metabolism ; Microvessels - drug effects ; Neurology ; patients ; permeability ; Pharmacology ; Proteomics ; secretion ; stroke ; tight junctions ; Tight Junctions - drug effects ; Tight Junctions - metabolism ; Vertebrates: nervous system and sense organs</subject><ispartof>Brain research, 2013-10, Vol.1534, p.87-94</ispartof><rights>Elsevier B.V.</rights><rights>2013 Elsevier B.V.</rights><rights>2014 INIST-CNRS</rights><rights>2013 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-f4fd553108f9fdcc1696b239bc35d9b51802bcfee88edbab7c882c473bb012963</citedby><cites>FETCH-LOGICAL-c543t-f4fd553108f9fdcc1696b239bc35d9b51802bcfee88edbab7c882c473bb012963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.brainres.2013.08.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27792499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23958343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Onodera, Hidetaka</creatorcontrib><creatorcontrib>Arito, Mitsumi</creatorcontrib><creatorcontrib>Sato, Toshiyuki</creatorcontrib><creatorcontrib>Ito, Hidemichi</creatorcontrib><creatorcontrib>Hashimoto, Takuo</creatorcontrib><creatorcontrib>Tanaka, Yuichiro</creatorcontrib><creatorcontrib>Kurokawa, Manae S</creatorcontrib><creatorcontrib>Okamoto, Kazuki</creatorcontrib><creatorcontrib>Suematsu, Naoya</creatorcontrib><creatorcontrib>Kato, Tomohiro</creatorcontrib><title>Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>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.</description><subject>actin</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood–brain barrier</subject><subject>brain</subject><subject>Brain - blood supply</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cells, Cultured</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>chemokines</subject><subject>cytoskeleton</subject><subject>Edaravone</subject><subject>endothelial cells</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>fluorescence</subject><subject>free radical scavengers</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gel electrophoresis</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>immunocytochemistry</subject><subject>interleukins</subject><subject>Lactic Acid - metabolism</subject><subject>Microvessels - drug effects</subject><subject>Neurology</subject><subject>patients</subject><subject>permeability</subject><subject>Pharmacology</subject><subject>Proteomics</subject><subject>secretion</subject><subject>stroke</subject><subject>tight junctions</subject><subject>Tight Junctions - drug effects</subject><subject>Tight Junctions - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhS0EokPhLxRvkNgk-JGHvUFUFS-pgkXp2rKda8YhiQc7iTT_HoeZgsSGlW3pu_ccn3sRuqKkpIQ2b_rSRO2nCKlkhPKSiJJQ-QjtqGhZ0bCKPEY7QkhTCCn5BXqWUp-fnEvyFF0wLmvBK75D_ZewwoDBObBzwsFh6HTUa5gAhwnvl1FP-LcUHr2NYdXJLoOOGKYuzHsYvB6whWFIOMIKeoAOmyPW-BDDDCHXYH3Id233z9ETp4cEL87nJbr_8P7bzafi9uvHzzfXt4WtKz4XrnJdXXNKhJOus5Y2sjHZsLG87qSpqSDMWAcgBHRGm9YKwWzVcmMIZbLhl-j1qW-W_blAmtXo02ZRTxCWpGjFm7qpKCMZbU5o_llKEZw6RD_qeFSUqC1n1auHnNWWsyJC5Zxz4dVZYzEjdH_KHoLNwKszkAPTg4t6sj795dpWskpujV6eOKeD0t9jZu7vslKdhyVr1tJMvDsRkDNbPUSVrIfJQudjnpnqgv-_27f_tLCDn3z29QOOkPqwxClPRFGVmCLqbtubbW0oJ5SynNMvb4W-2g</recordid><startdate>20131009</startdate><enddate>20131009</enddate><creator>Onodera, Hidetaka</creator><creator>Arito, Mitsumi</creator><creator>Sato, Toshiyuki</creator><creator>Ito, Hidemichi</creator><creator>Hashimoto, Takuo</creator><creator>Tanaka, Yuichiro</creator><creator>Kurokawa, Manae S</creator><creator>Okamoto, Kazuki</creator><creator>Suematsu, Naoya</creator><creator>Kato, Tomohiro</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20131009</creationdate><title>Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach</title><author>Onodera, Hidetaka ; Arito, Mitsumi ; Sato, Toshiyuki ; Ito, Hidemichi ; Hashimoto, Takuo ; Tanaka, Yuichiro ; Kurokawa, Manae S ; Okamoto, Kazuki ; Suematsu, Naoya ; Kato, Tomohiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-f4fd553108f9fdcc1696b239bc35d9b51802bcfee88edbab7c882c473bb012963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>actin</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood–brain barrier</topic><topic>brain</topic><topic>Brain - blood supply</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cells, Cultured</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>chemokines</topic><topic>cytoskeleton</topic><topic>Edaravone</topic><topic>endothelial cells</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>fluorescence</topic><topic>free radical scavengers</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gel electrophoresis</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>immunocytochemistry</topic><topic>interleukins</topic><topic>Lactic Acid - metabolism</topic><topic>Microvessels - drug effects</topic><topic>Neurology</topic><topic>patients</topic><topic>permeability</topic><topic>Pharmacology</topic><topic>Proteomics</topic><topic>secretion</topic><topic>stroke</topic><topic>tight junctions</topic><topic>Tight Junctions - drug effects</topic><topic>Tight Junctions - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Onodera, Hidetaka</creatorcontrib><creatorcontrib>Arito, Mitsumi</creatorcontrib><creatorcontrib>Sato, Toshiyuki</creatorcontrib><creatorcontrib>Ito, Hidemichi</creatorcontrib><creatorcontrib>Hashimoto, Takuo</creatorcontrib><creatorcontrib>Tanaka, Yuichiro</creatorcontrib><creatorcontrib>Kurokawa, Manae S</creatorcontrib><creatorcontrib>Okamoto, Kazuki</creatorcontrib><creatorcontrib>Suematsu, Naoya</creatorcontrib><creatorcontrib>Kato, Tomohiro</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Onodera, Hidetaka</au><au>Arito, Mitsumi</au><au>Sato, Toshiyuki</au><au>Ito, Hidemichi</au><au>Hashimoto, Takuo</au><au>Tanaka, Yuichiro</au><au>Kurokawa, Manae S</au><au>Okamoto, Kazuki</au><au>Suematsu, Naoya</au><au>Kato, Tomohiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2013-10-09</date><risdate>2013</risdate><volume>1534</volume><spage>87</spage><epage>94</epage><pages>87-94</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>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.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>23958343</pmid><doi>10.1016/j.brainres.2013.08.019</doi><tpages>8</tpages></addata></record> |
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| subjects | actin Antipyrine - analogs & derivatives Antipyrine - pharmacology Biological and medical sciences Blood–brain barrier brain Brain - blood supply Brain - drug effects Brain - metabolism Cells, Cultured Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges chemokines cytoskeleton Edaravone endothelial cells Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelium Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism fluorescence free radical scavengers Fundamental and applied biological sciences. Psychology gel electrophoresis HeLa Cells Humans immunocytochemistry interleukins Lactic Acid - metabolism Microvessels - drug effects Neurology patients permeability Pharmacology Proteomics secretion stroke tight junctions Tight Junctions - drug effects Tight Junctions - metabolism Vertebrates: nervous system and sense organs |
| title | Novel effects of edaravone on human brain microvascular endothelial cells revealed by a proteomic approach |
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