Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2

Variation in the lipid moiety of the verotoxin (VT) receptor glycosphingolipid, globotriaosyl ceramide (Gb3) can modulate toxin binding. The binding of VT1 and VT2 to C18 and C22 alpha hydroxy and nonhydroxy fatty acid isoforms of Gb3 were compared using a receptor ELISA and a 125I-labeled toxin/gly...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Neurochemical research 2002-08, Vol.27 (7-8), p.807-813
Hauptverfasser: BINNINGTON, Beth, LINGWOOD, Daniel, NUTIKKA, Anita, LINGWOOD, Clifford A
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 813
container_issue 7-8
container_start_page 807
container_title Neurochemical research
container_volume 27
creator BINNINGTON, Beth
LINGWOOD, Daniel
NUTIKKA, Anita
LINGWOOD, Clifford A
description Variation in the lipid moiety of the verotoxin (VT) receptor glycosphingolipid, globotriaosyl ceramide (Gb3) can modulate toxin binding. The binding of VT1 and VT2 to C18 and C22 alpha hydroxy and nonhydroxy fatty acid isoforms of Gb3 were compared using a receptor ELISA and a 125I-labeled toxin/glycolipid microtitre plate direct binding assay. Increased binding to the hydroxylated species, particularly C220H, was observed for both toxins. Increased RELISA binding at low glycolipid concentrations only, suggested the binding affinity is increased following Gb3 fatty acid hydroxylation. Nonlinear regression analysis of direct binding assay to these Gb3 isoforms confirmed the increased affinity of both toxins for the C22 hydroxylated Gb3. The capacity was also significantly increased. The increased binding of VTs for hydroxylated fatty acid Gb3 isoforms may be a factor in the selective renal pathology which can follow systemic verotoxemia, particularly in the mouse model. The more pronounced effect at lower glycolipid concentrations prompted investigation of VT1 binding affinity at different Gb3 concentrations. Unexpectedly, the VT1 Kd for Gb3 was found to decrease as an inverse function of the Gb3 concentration. This shows that glycolipids have "nonclassical" receptor properties.
doi_str_mv 10.1023/A:1020261125008
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72156745</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>18596016</sourcerecordid><originalsourceid>FETCH-LOGICAL-c360t-510f7421a5d16977a1e59427b734bd62adc1816ced4686fa44451f42b4c965ad3</originalsourceid><addsrcrecordid>eNqF0MlKA0EQBuBGFI3L2Zv0RW-jXb1mvElwA8GLnkNNL6bDZFqnO-I8li_iMxkxojeh4Kfg46coQg6BnQLj4uzifBWMawCuGBtvkBEoIypdM7FJRkxoWQmo2Q7ZzXnOGDDGYZvsABdGcjAjMr8MwdtCU6BPbWpS6SOmPLTU-h4X0XkasJSBoo2OfrxXs8H16W1oscTU0dWUmadN7Fzsnmgz0Fffp5LeYkeBYuf-7HyfbAVssz9Y5x55vLp8mNxUd_fXt5OLu8oKzUqlgIWv41A50LUxCF7VkpvGCNk4zdFZGIO23kk91gGllAqC5I20tVboxB45-e597tPL0ucyXcRsfdti59MyTw0HpY1U_0IYq1oz0Ct4tIbLZuHd9LmPC-yH6c8bV-B4DTBbbEOPnY3514naSKFq8QmtCIGF</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18596016</pqid></control><display><type>article</type><title>Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>BINNINGTON, Beth ; LINGWOOD, Daniel ; NUTIKKA, Anita ; LINGWOOD, Clifford A</creator><creatorcontrib>BINNINGTON, Beth ; LINGWOOD, Daniel ; NUTIKKA, Anita ; LINGWOOD, Clifford A</creatorcontrib><description>Variation in the lipid moiety of the verotoxin (VT) receptor glycosphingolipid, globotriaosyl ceramide (Gb3) can modulate toxin binding. The binding of VT1 and VT2 to C18 and C22 alpha hydroxy and nonhydroxy fatty acid isoforms of Gb3 were compared using a receptor ELISA and a 125I-labeled toxin/glycolipid microtitre plate direct binding assay. Increased binding to the hydroxylated species, particularly C220H, was observed for both toxins. Increased RELISA binding at low glycolipid concentrations only, suggested the binding affinity is increased following Gb3 fatty acid hydroxylation. Nonlinear regression analysis of direct binding assay to these Gb3 isoforms confirmed the increased affinity of both toxins for the C22 hydroxylated Gb3. The capacity was also significantly increased. The increased binding of VTs for hydroxylated fatty acid Gb3 isoforms may be a factor in the selective renal pathology which can follow systemic verotoxemia, particularly in the mouse model. The more pronounced effect at lower glycolipid concentrations prompted investigation of VT1 binding affinity at different Gb3 concentrations. Unexpectedly, the VT1 Kd for Gb3 was found to decrease as an inverse function of the Gb3 concentration. This shows that glycolipids have "nonclassical" receptor properties.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1023/A:1020261125008</identifier><identifier>PMID: 12374217</identifier><identifier>CODEN: NEREDZ</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Biological and medical sciences ; Chromatography, Thin Layer ; Enzyme-Linked Immunosorbent Assay ; Fundamental and applied biological sciences. Psychology ; Hydroxylation ; Protein Binding ; Shiga Toxins - metabolism ; Trihexosylceramides - metabolism</subject><ispartof>Neurochemical research, 2002-08, Vol.27 (7-8), p.807-813</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-510f7421a5d16977a1e59427b734bd62adc1816ced4686fa44451f42b4c965ad3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=13974359$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12374217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BINNINGTON, Beth</creatorcontrib><creatorcontrib>LINGWOOD, Daniel</creatorcontrib><creatorcontrib>NUTIKKA, Anita</creatorcontrib><creatorcontrib>LINGWOOD, Clifford A</creatorcontrib><title>Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><description>Variation in the lipid moiety of the verotoxin (VT) receptor glycosphingolipid, globotriaosyl ceramide (Gb3) can modulate toxin binding. The binding of VT1 and VT2 to C18 and C22 alpha hydroxy and nonhydroxy fatty acid isoforms of Gb3 were compared using a receptor ELISA and a 125I-labeled toxin/glycolipid microtitre plate direct binding assay. Increased binding to the hydroxylated species, particularly C220H, was observed for both toxins. Increased RELISA binding at low glycolipid concentrations only, suggested the binding affinity is increased following Gb3 fatty acid hydroxylation. Nonlinear regression analysis of direct binding assay to these Gb3 isoforms confirmed the increased affinity of both toxins for the C22 hydroxylated Gb3. The capacity was also significantly increased. The increased binding of VTs for hydroxylated fatty acid Gb3 isoforms may be a factor in the selective renal pathology which can follow systemic verotoxemia, particularly in the mouse model. The more pronounced effect at lower glycolipid concentrations prompted investigation of VT1 binding affinity at different Gb3 concentrations. Unexpectedly, the VT1 Kd for Gb3 was found to decrease as an inverse function of the Gb3 concentration. This shows that glycolipids have "nonclassical" receptor properties.</description><subject>Biological and medical sciences</subject><subject>Chromatography, Thin Layer</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hydroxylation</subject><subject>Protein Binding</subject><subject>Shiga Toxins - metabolism</subject><subject>Trihexosylceramides - metabolism</subject><issn>0364-3190</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0MlKA0EQBuBGFI3L2Zv0RW-jXb1mvElwA8GLnkNNL6bDZFqnO-I8li_iMxkxojeh4Kfg46coQg6BnQLj4uzifBWMawCuGBtvkBEoIypdM7FJRkxoWQmo2Q7ZzXnOGDDGYZvsABdGcjAjMr8MwdtCU6BPbWpS6SOmPLTU-h4X0XkasJSBoo2OfrxXs8H16W1oscTU0dWUmadN7Fzsnmgz0Fffp5LeYkeBYuf-7HyfbAVssz9Y5x55vLp8mNxUd_fXt5OLu8oKzUqlgIWv41A50LUxCF7VkpvGCNk4zdFZGIO23kk91gGllAqC5I20tVboxB45-e597tPL0ucyXcRsfdti59MyTw0HpY1U_0IYq1oz0Ct4tIbLZuHd9LmPC-yH6c8bV-B4DTBbbEOPnY3514naSKFq8QmtCIGF</recordid><startdate>20020801</startdate><enddate>20020801</enddate><creator>BINNINGTON, Beth</creator><creator>LINGWOOD, Daniel</creator><creator>NUTIKKA, Anita</creator><creator>LINGWOOD, Clifford A</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20020801</creationdate><title>Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2</title><author>BINNINGTON, Beth ; LINGWOOD, Daniel ; NUTIKKA, Anita ; LINGWOOD, Clifford A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-510f7421a5d16977a1e59427b734bd62adc1816ced4686fa44451f42b4c965ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Biological and medical sciences</topic><topic>Chromatography, Thin Layer</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hydroxylation</topic><topic>Protein Binding</topic><topic>Shiga Toxins - metabolism</topic><topic>Trihexosylceramides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BINNINGTON, Beth</creatorcontrib><creatorcontrib>LINGWOOD, Daniel</creatorcontrib><creatorcontrib>NUTIKKA, Anita</creatorcontrib><creatorcontrib>LINGWOOD, Clifford A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BINNINGTON, Beth</au><au>LINGWOOD, Daniel</au><au>NUTIKKA, Anita</au><au>LINGWOOD, Clifford A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2</atitle><jtitle>Neurochemical research</jtitle><addtitle>Neurochem Res</addtitle><date>2002-08-01</date><risdate>2002</risdate><volume>27</volume><issue>7-8</issue><spage>807</spage><epage>813</epage><pages>807-813</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><coden>NEREDZ</coden><abstract>Variation in the lipid moiety of the verotoxin (VT) receptor glycosphingolipid, globotriaosyl ceramide (Gb3) can modulate toxin binding. The binding of VT1 and VT2 to C18 and C22 alpha hydroxy and nonhydroxy fatty acid isoforms of Gb3 were compared using a receptor ELISA and a 125I-labeled toxin/glycolipid microtitre plate direct binding assay. Increased binding to the hydroxylated species, particularly C220H, was observed for both toxins. Increased RELISA binding at low glycolipid concentrations only, suggested the binding affinity is increased following Gb3 fatty acid hydroxylation. Nonlinear regression analysis of direct binding assay to these Gb3 isoforms confirmed the increased affinity of both toxins for the C22 hydroxylated Gb3. The capacity was also significantly increased. The increased binding of VTs for hydroxylated fatty acid Gb3 isoforms may be a factor in the selective renal pathology which can follow systemic verotoxemia, particularly in the mouse model. The more pronounced effect at lower glycolipid concentrations prompted investigation of VT1 binding affinity at different Gb3 concentrations. Unexpectedly, the VT1 Kd for Gb3 was found to decrease as an inverse function of the Gb3 concentration. This shows that glycolipids have "nonclassical" receptor properties.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>12374217</pmid><doi>10.1023/A:1020261125008</doi><tpages>7</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0364-3190
ispartof Neurochemical research, 2002-08, Vol.27 (7-8), p.807-813
issn 0364-3190
1573-6903
language eng
recordid cdi_proquest_miscellaneous_72156745
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects Biological and medical sciences
Chromatography, Thin Layer
Enzyme-Linked Immunosorbent Assay
Fundamental and applied biological sciences. Psychology
Hydroxylation
Protein Binding
Shiga Toxins - metabolism
Trihexosylceramides - metabolism
title Effect of globotriaosyl ceramide fatty acid α-hydroxylation on the binding by verotoxin 1 and verotoxin 2
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T02%3A18%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20globotriaosyl%20ceramide%20fatty%20acid%20%CE%B1-hydroxylation%20on%20the%20binding%20by%20verotoxin%201%20and%20verotoxin%202&rft.jtitle=Neurochemical%20research&rft.au=BINNINGTON,%20Beth&rft.date=2002-08-01&rft.volume=27&rft.issue=7-8&rft.spage=807&rft.epage=813&rft.pages=807-813&rft.issn=0364-3190&rft.eissn=1573-6903&rft.coden=NEREDZ&rft_id=info:doi/10.1023/A:1020261125008&rft_dat=%3Cproquest_pubme%3E18596016%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18596016&rft_id=info:pmid/12374217&rfr_iscdi=true