Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis
Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 ( ABCC1) and 2 ( ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression...
Gespeichert in:
Veröffentlicht in: | Epilepsy research 2006-03, Vol.68 (3), p.213-228 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 228 |
---|---|
container_issue | 3 |
container_start_page | 213 |
container_title | Epilepsy research |
container_volume | 68 |
creator | Kubota, Hisashi Ishihara, Hideyuki Langmann, Thomas Schmitz, Gerd Stieger, Bruno Wieser, Heinz-Gregor Yonekawa, Yasuhiro Frei, Karl |
description | Multidrug resistance protein, also referred as P-glycoprotein (P-gp,
MDR1;
ABCB1) and multidrug resistance-associated protein (MRP) 1 (
ABCC1) and 2 (
ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that
MDR1,
MRP1 as well as
MRP5 (ABCC5) and
MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood–brain barrier (BBB). |
doi_str_mv | 10.1016/j.eplepsyres.2005.11.011 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67702482</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0920121105002925</els_id><sourcerecordid>67702482</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-a826dafcde7197525614413a68922cb0f302b066dbe9458dee10992ed5c794e93</originalsourceid><addsrcrecordid>eNqFkc-O1SAUxonRONfRVzCs3LVyKKXtUse_ySS60DWhcDrDDS0V6E3uM_mSctObzNIVB_I75zsfHyEUWA0M5PtjjavHNZ0jppoz1tYANQN4Rg7Qd7ySvRDPyYENnFXAAW7Iq5SOjLGOCfGS3IBsJLCeH8jfTy7l6MYtu7BQvVg6bYu5XLSnuhQnl880TPRn9eDPJqwxZHQ7OW8-Oxu3B1rWKGP0YrDSKQXjdEZLr2yihX_cZr3QMepSz87EcNLJbF5HiosN-RG9K4IGvd9xt67B6Hktj8l4jKEIvCYvJu0Tvrmet-T3l8-_7r5V9z--fr_7cF8Z0fS50j2XVk_GYgdD1_JWghDQaNkPnJuRTQ3jI5PSjjiItreIwIaBo21NNwgcmlvybp9bDPzZMGU1u3RZTS8YtqRk1zEuel7AfgeLn5QiTmqNbtbxrICpS1DqqJ6CUpegFIAqQZXWt1eNbZzRPjVekynAxx3A4vTkMKpkHJYfti6iycoG93-Vf7TJr_M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67702482</pqid></control><display><type>article</type><title>Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Kubota, Hisashi ; Ishihara, Hideyuki ; Langmann, Thomas ; Schmitz, Gerd ; Stieger, Bruno ; Wieser, Heinz-Gregor ; Yonekawa, Yasuhiro ; Frei, Karl</creator><creatorcontrib>Kubota, Hisashi ; Ishihara, Hideyuki ; Langmann, Thomas ; Schmitz, Gerd ; Stieger, Bruno ; Wieser, Heinz-Gregor ; Yonekawa, Yasuhiro ; Frei, Karl</creatorcontrib><description>Multidrug resistance protein, also referred as P-glycoprotein (P-gp,
MDR1;
ABCB1) and multidrug resistance-associated protein (MRP) 1 (
ABCC1) and 2 (
ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that
MDR1,
MRP1 as well as
MRP5 (ABCC5) and
MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood–brain barrier (BBB).</description><identifier>ISSN: 0920-1211</identifier><identifier>EISSN: 1872-6844</identifier><identifier>DOI: 10.1016/j.eplepsyres.2005.11.011</identifier><identifier>PMID: 16361082</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Adult ; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism ; Blood–brain barrier ; Cell Line, Tumor ; Cells, Cultured ; Child ; Drug resistance ; Drug Resistance, Multiple - physiology ; Endothelial Cells - metabolism ; Endothelium, Vascular - cytology ; Endothelium, Vascular - metabolism ; Epilepsy ; Epilepsy, Temporal Lobe - metabolism ; Epilepsy, Temporal Lobe - surgery ; Female ; Hippocampal sclerosis ; Hippocampus - metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multidrug resistance-associated proteins ; Multidrug Resistance-Associated Proteins - metabolism ; P-glycoprotein ; RNA, Messenger ; Sclerosis</subject><ispartof>Epilepsy research, 2006-03, Vol.68 (3), p.213-228</ispartof><rights>2005 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-a826dafcde7197525614413a68922cb0f302b066dbe9458dee10992ed5c794e93</citedby><cites>FETCH-LOGICAL-c438t-a826dafcde7197525614413a68922cb0f302b066dbe9458dee10992ed5c794e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.eplepsyres.2005.11.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16361082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kubota, Hisashi</creatorcontrib><creatorcontrib>Ishihara, Hideyuki</creatorcontrib><creatorcontrib>Langmann, Thomas</creatorcontrib><creatorcontrib>Schmitz, Gerd</creatorcontrib><creatorcontrib>Stieger, Bruno</creatorcontrib><creatorcontrib>Wieser, Heinz-Gregor</creatorcontrib><creatorcontrib>Yonekawa, Yasuhiro</creatorcontrib><creatorcontrib>Frei, Karl</creatorcontrib><title>Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis</title><title>Epilepsy research</title><addtitle>Epilepsy Res</addtitle><description>Multidrug resistance protein, also referred as P-glycoprotein (P-gp,
MDR1;
ABCB1) and multidrug resistance-associated protein (MRP) 1 (
ABCC1) and 2 (
ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that
MDR1,
MRP1 as well as
MRP5 (ABCC5) and
MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood–brain barrier (BBB).</description><subject>Adolescent</subject><subject>Adult</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Blood–brain barrier</subject><subject>Cell Line, Tumor</subject><subject>Cells, Cultured</subject><subject>Child</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple - physiology</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Epilepsy</subject><subject>Epilepsy, Temporal Lobe - metabolism</subject><subject>Epilepsy, Temporal Lobe - surgery</subject><subject>Female</subject><subject>Hippocampal sclerosis</subject><subject>Hippocampus - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multidrug resistance-associated proteins</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>P-glycoprotein</subject><subject>RNA, Messenger</subject><subject>Sclerosis</subject><issn>0920-1211</issn><issn>1872-6844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O1SAUxonRONfRVzCs3LVyKKXtUse_ySS60DWhcDrDDS0V6E3uM_mSctObzNIVB_I75zsfHyEUWA0M5PtjjavHNZ0jppoz1tYANQN4Rg7Qd7ySvRDPyYENnFXAAW7Iq5SOjLGOCfGS3IBsJLCeH8jfTy7l6MYtu7BQvVg6bYu5XLSnuhQnl880TPRn9eDPJqwxZHQ7OW8-Oxu3B1rWKGP0YrDSKQXjdEZLr2yihX_cZr3QMepSz87EcNLJbF5HiosN-RG9K4IGvd9xt67B6Hktj8l4jKEIvCYvJu0Tvrmet-T3l8-_7r5V9z--fr_7cF8Z0fS50j2XVk_GYgdD1_JWghDQaNkPnJuRTQ3jI5PSjjiItreIwIaBo21NNwgcmlvybp9bDPzZMGU1u3RZTS8YtqRk1zEuel7AfgeLn5QiTmqNbtbxrICpS1DqqJ6CUpegFIAqQZXWt1eNbZzRPjVekynAxx3A4vTkMKpkHJYfti6iycoG93-Vf7TJr_M</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Kubota, Hisashi</creator><creator>Ishihara, Hideyuki</creator><creator>Langmann, Thomas</creator><creator>Schmitz, Gerd</creator><creator>Stieger, Bruno</creator><creator>Wieser, Heinz-Gregor</creator><creator>Yonekawa, Yasuhiro</creator><creator>Frei, Karl</creator><general>Elsevier B.V</general><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>20060301</creationdate><title>Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis</title><author>Kubota, Hisashi ; Ishihara, Hideyuki ; Langmann, Thomas ; Schmitz, Gerd ; Stieger, Bruno ; Wieser, Heinz-Gregor ; Yonekawa, Yasuhiro ; Frei, Karl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-a826dafcde7197525614413a68922cb0f302b066dbe9458dee10992ed5c794e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</topic><topic>Blood–brain barrier</topic><topic>Cell Line, Tumor</topic><topic>Cells, Cultured</topic><topic>Child</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple - physiology</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Epilepsy</topic><topic>Epilepsy, Temporal Lobe - metabolism</topic><topic>Epilepsy, Temporal Lobe - surgery</topic><topic>Female</topic><topic>Hippocampal sclerosis</topic><topic>Hippocampus - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multidrug resistance-associated proteins</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>P-glycoprotein</topic><topic>RNA, Messenger</topic><topic>Sclerosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kubota, Hisashi</creatorcontrib><creatorcontrib>Ishihara, Hideyuki</creatorcontrib><creatorcontrib>Langmann, Thomas</creatorcontrib><creatorcontrib>Schmitz, Gerd</creatorcontrib><creatorcontrib>Stieger, Bruno</creatorcontrib><creatorcontrib>Wieser, Heinz-Gregor</creatorcontrib><creatorcontrib>Yonekawa, Yasuhiro</creatorcontrib><creatorcontrib>Frei, Karl</creatorcontrib><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>Epilepsy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kubota, Hisashi</au><au>Ishihara, Hideyuki</au><au>Langmann, Thomas</au><au>Schmitz, Gerd</au><au>Stieger, Bruno</au><au>Wieser, Heinz-Gregor</au><au>Yonekawa, Yasuhiro</au><au>Frei, Karl</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis</atitle><jtitle>Epilepsy research</jtitle><addtitle>Epilepsy Res</addtitle><date>2006-03-01</date><risdate>2006</risdate><volume>68</volume><issue>3</issue><spage>213</spage><epage>228</epage><pages>213-228</pages><issn>0920-1211</issn><eissn>1872-6844</eissn><abstract>Multidrug resistance protein, also referred as P-glycoprotein (P-gp,
MDR1;
ABCB1) and multidrug resistance-associated protein (MRP) 1 (
ABCC1) and 2 (
ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that
MDR1,
MRP1 as well as
MRP5 (ABCC5) and
MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood–brain barrier (BBB).</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>16361082</pmid><doi>10.1016/j.eplepsyres.2005.11.011</doi><tpages>16</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0920-1211 |
ispartof | Epilepsy research, 2006-03, Vol.68 (3), p.213-228 |
issn | 0920-1211 1872-6844 |
language | eng |
recordid | cdi_proquest_miscellaneous_67702482 |
source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Adolescent Adult ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Blood–brain barrier Cell Line, Tumor Cells, Cultured Child Drug resistance Drug Resistance, Multiple - physiology Endothelial Cells - metabolism Endothelium, Vascular - cytology Endothelium, Vascular - metabolism Epilepsy Epilepsy, Temporal Lobe - metabolism Epilepsy, Temporal Lobe - surgery Female Hippocampal sclerosis Hippocampus - metabolism Humans Immunohistochemistry Male Middle Aged Multidrug resistance-associated proteins Multidrug Resistance-Associated Proteins - metabolism P-glycoprotein RNA, Messenger Sclerosis |
title | Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T09%3A14%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Distribution%20and%20functional%20activity%20of%20P-glycoprotein%20and%20multidrug%20resistance-associated%20proteins%20in%20human%20brain%20microvascular%20endothelial%20cells%20in%20hippocampal%20sclerosis&rft.jtitle=Epilepsy%20research&rft.au=Kubota,%20Hisashi&rft.date=2006-03-01&rft.volume=68&rft.issue=3&rft.spage=213&rft.epage=228&rft.pages=213-228&rft.issn=0920-1211&rft.eissn=1872-6844&rft_id=info:doi/10.1016/j.eplepsyres.2005.11.011&rft_dat=%3Cproquest_cross%3E67702482%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67702482&rft_id=info:pmid/16361082&rft_els_id=S0920121105002925&rfr_iscdi=true |