Pantethine alters lipid composition and cholesterol content of membrane rafts, with down-regulation of cxcl12-induced t cell migration
Identifieur interne : 000197 ( Hal/Checkpoint ); précédent : 000196; suivant : 000198Pantethine alters lipid composition and cholesterol content of membrane rafts, with down-regulation of cxcl12-induced t cell migration
Auteurs : Manuel Van Gijsel-Bonnello [France] ; Niyazi Acar [France] ; Yves Molino [France] ; Lionel Bretillon [France] ; Michel Khrestchatisky [France] ; Max De Reggi [France] ; Bouchra Gharib [France]Source :
- Journal of Cellular Physiology [ 0021-9541 ] ; 2015.
English descriptors
Abstract
Pantethine, a natural low-molecular-weight thiol, shows broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We showed recently that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: i) CXCL12 binding to its target cells; ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells (LAT) molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which palmitoylation level was reduced. In conclusion, the results presented here, together with previously published findings, indicate that, due to its pleiotropic action, pantethine can down-regulate the multifaceted process leading to pathogenic T cell activation and migration.
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DOI: 10.1002/jcp.24971
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NICN</orgName> <orgName type="acronym">NICN</orgName> <date type="start">2012</date> <desc> <address> <addrLine>CS80011 51 Bd Pierre Dramard13344 Marseille Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.nicn.fr/</ref> </desc> <listRelation> <relation name="UMR7259" active="#struct-92114" type="direct"></relation> <relation name="UMR7259" active="#struct-303623" type="direct"></relation> <relation name="UMR7259" active="#struct-441569" type="direct"></relation> <relation name="UMR6184" active="#struct-5033" type="direct"></relation> <relation name="UMR7259" active="#struct-198056" type="direct"></relation> </listRelation><tutelles><tutelle name="UMR7259" active="#struct-92114" type="direct"><org type="institution" xml:id="struct-92114" status="VALID"> <orgName>Institut National de la Recherche Agronomique</orgName> <orgName type="acronym">INRA</orgName> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.inra.fr</ref> </desc></org></tutelle><tutelle name="UMR7259" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle name="UMR7259" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc></org></tutelle><tutelle name="UMR6184" active="#struct-5033" type="direct"><org type="institution" xml:id="struct-5033" status="OLD"> <idno type="IdRef">026402882</idno> <orgName>Université de la Méditerranée - Aix-Marseille 2</orgName> <date type="start">1969</date> <date type="end">2011</date> <desc> <address> <addrLine>58, boulevard Charles Livon - 13284 Marseille cedex 07</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univmed.fr/</ref> </desc></org></tutelle><tutelle name="UMR7259" active="#struct-198056" type="direct"><org type="institution" xml:id="struct-198056" status="VALID"> <idno type="IdRef">15863621X</idno> <idno type="ISNI">0000 0001 2176 4817</idno> <orgName>Aix Marseille Université</orgName> <orgName type="acronym">AMU</orgName> <date type="start">2012-01-01</date> <desc> <address> <addrLine>Aix-Marseille UniversitéJardins du Pharo58 Boulevard Charles Livon13284 Marseille cedex 7</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-amu.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Marseille</settlement><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author></analytic><idno type="DOI">10.1002/jcp.24971</idno><series><title level="j">Journal of Cellular Physiology</title><idno type="ISSN">0021-9541</idno><imprint><date type="datePub">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>cell redox status</term><term>lipid rafts</term><term>t cell migration</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pantethine, a natural low-molecular-weight thiol, shows broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We showed recently that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: i) CXCL12 binding to its target cells; ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells (LAT) molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which palmitoylation level was reduced. In conclusion, the results presented here, together with previously published findings, indicate that, due to its pleiotropic action, pantethine can down-regulate the multifaceted process leading to pathogenic T cell activation and migration.</div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">Pantethine alters lipid composition and cholesterol content of membrane rafts, with down-regulation of cxcl12-induced t cell migration</title> <author role="aut"> <persName> <forename type="first">Manuel</forename> <surname>van Gijsel-Bonnello</surname> </persName> <idno type="halauthorid">1224984</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Niyazi</forename> <surname>Acar</surname> </persName> <email type="md5">53c83cf408d06b6cbc7b0209007a0ed4</email> <email type="domain">dijon.inra.fr</email> <idno type="halauthorid">816814</idno> <affiliation ref="#struct-106335"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Yves</forename> <surname>Molino</surname> </persName> <idno type="halauthorid">1224985</idno> <affiliation ref="#struct-435884"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Lionel</forename> <surname>Bretillon</surname> </persName> <email type="md5">a767468be1852da5ef8621a7a7e37d5f</email> <email type="domain">dijon.inra.fr</email> <idno type="halauthorid">816605</idno> <affiliation ref="#struct-106335"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Michel</forename> <surname>Khrestchatisky</surname> </persName> <idno type="halauthorid">122675</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Max</forename> <surname>De Reggi</surname> </persName> <idno type="halauthorid">370482</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Bouchra</forename> <surname>Gharib</surname> </persName> <email type="md5">6d4a2cf2c248ed1a63b242cbf11f7abf</email> <email type="domain">univ-amu.fr</email> <idno type="halauthorid">1224986</idno> <affiliation ref="#struct-199350"></affiliation> </author> <editor role="depositor"> <persName> <forename>Archive Ouverte</forename> <surname>ProdInra</surname> </persName> <email type="md5">859d2cba2c64f5bbc2add42f2b9992d1</email> <email type="domain">inra.fr</email> </editor> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2015-10-01 20:11:49</date> <date type="whenModified">2015-12-14 20:17:43</date> <date type="whenReleased">2015-10-01 20:11:49</date> <date type="whenProduced">2015</date> </edition> <respStmt> <resp>contributor</resp> <name key="132775"> <persName> <forename>Archive Ouverte</forename> <surname>ProdInra</surname> </persName> <email type="md5">859d2cba2c64f5bbc2add42f2b9992d1</email> <email type="domain">inra.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">hal-01208113</idno> <idno type="halUri">https://hal.archives-ouvertes.fr/hal-01208113</idno> <idno type="halBibtex">vangijselbonnello:hal-01208113</idno> <idno type="halRefHtml">Journal of Cellular Physiology, Wiley, 2015, 2015 (230), pp.2415-2425. <10.1002/jcp.24971></idno> <idno type="halRef">Journal of Cellular Physiology, Wiley, 2015, 2015 (230), pp.2415-2425. <10.1002/jcp.24971></idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> <idno type="stamp" n="UNIV-BOURGOGNE">Université de Bourgogne</idno> <idno type="stamp" n="INRA">INRA - Institut national de la recherche agronomique</idno> <idno type="stamp" n="UNIV-AMU">Aix Marseille Université</idno> <idno type="stamp" n="CSGA" p="UNIV-BOURGOGNE">Centre des Sciences du Goût et de l'Alimentation</idno> </seriesStmt> <notesStmt> <note type="audience" n="1">Not set</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Pantethine alters lipid composition and cholesterol content of membrane rafts, with down-regulation of cxcl12-induced t cell migration</title> <author role="aut"> <persName> <forename type="first">Manuel</forename> <surname>van Gijsel-Bonnello</surname> </persName> <idno type="halauthorid">1224984</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Niyazi</forename> <surname>Acar</surname> </persName> <email type="md5">53c83cf408d06b6cbc7b0209007a0ed4</email> <email type="domain">dijon.inra.fr</email> <idno type="halauthorid">816814</idno> <affiliation ref="#struct-106335"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Yves</forename> <surname>Molino</surname> </persName> <idno type="halauthorid">1224985</idno> <affiliation ref="#struct-435884"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Lionel</forename> <surname>Bretillon</surname> </persName> <email type="md5">a767468be1852da5ef8621a7a7e37d5f</email> <email type="domain">dijon.inra.fr</email> <idno type="halauthorid">816605</idno> <affiliation ref="#struct-106335"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Michel</forename> <surname>Khrestchatisky</surname> </persName> <idno type="halauthorid">122675</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Max</forename> <surname>De Reggi</surname> </persName> <idno type="halauthorid">370482</idno> <affiliation ref="#struct-199350"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Bouchra</forename> <surname>Gharib</surname> </persName> <email type="md5">6d4a2cf2c248ed1a63b242cbf11f7abf</email> <email type="domain">univ-amu.fr</email> <idno type="halauthorid">1224986</idno> <affiliation ref="#struct-199350"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">5912</idno> <idno type="issn">0021-9541</idno> <idno type="eissn">1097-4652</idno> <title level="j">Journal of Cellular Physiology</title> <imprint> <publisher>Wiley</publisher> <biblScope unit="volume">2015</biblScope> <biblScope unit="issue">230</biblScope> <biblScope unit="pp">2415-2425</biblScope> <date type="datePub">2015</date> </imprint> </monogr> <idno type="doi">10.1002/jcp.24971</idno> <idno type="prodinra">309022</idno> <idno type="pubmed">25728249</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">cell redox status</term> <term xml:lang="en">lipid rafts</term> <term xml:lang="en">t cell migration</term> </keywords> <classCode scheme="halDomain" n="sdv.mhep.phy">Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en">Pantethine, a natural low-molecular-weight thiol, shows broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We showed recently that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: i) CXCL12 binding to its target cells; ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells (LAT) molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which palmitoylation level was reduced. In conclusion, the results presented here, together with previously published findings, indicate that, due to its pleiotropic action, pantethine can down-regulate the multifaceted process leading to pathogenic T cell activation and migration.</abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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