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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Protection against cerebral malaria by the low-molecular-weight thiol pantethine</title><author><name sortKey="Penet, Marie France" sort="Penet, Marie France" uniqKey="Penet M" first="Marie-France" last="Penet">Marie-France Penet</name><affiliation><nlm:aff id="aff1">*Centre de Résonance Magnétique Biologique et Médicale, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6612,</nlm:aff></affiliation></author><author><name sortKey="Abou Hamdan, Mhamad" sort="Abou Hamdan, Mhamad" uniqKey="Abou Hamdan M" first="Mhamad" last="Abou-Hamdan">Mhamad Abou-Hamdan</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Coltel, Nicolas" sort="Coltel, Nicolas" uniqKey="Coltel N" first="Nicolas" last="Coltel">Nicolas Coltel</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Unité des Rickettsies et des Pathogènes émergents, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6020, Université de la Méditerranée, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Cornille, Emilie" sort="Cornille, Emilie" uniqKey="Cornille E" first="Emilie" last="Cornille">Emilie Cornille</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Grau, Georges E" sort="Grau, Georges E" uniqKey="Grau G" first="Georges E." last="Grau">Georges E. Grau</name><affiliation><nlm:aff id="aff4">Vascular Immunology Unit, Department of Pathology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney NSW 2402, Australia</nlm:aff></affiliation></author><author><name sortKey="De Reggi, Max" sort="De Reggi, Max" uniqKey="De Reggi M" first="Max" last="De Reggi">Max De Reggi</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Gharib, Bouchra" sort="Gharib, Bouchra" uniqKey="Gharib B" first="Bouchra" last="Gharib">Bouchra Gharib</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18195363</idno><idno type="pmc">2234136</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234136</idno><idno type="RBID">PMC:2234136</idno><idno type="doi">10.1073/pnas.0706867105</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">001B60</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B60</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Protection against cerebral malaria by the low-molecular-weight thiol pantethine</title><author><name sortKey="Penet, Marie France" sort="Penet, Marie France" uniqKey="Penet M" first="Marie-France" last="Penet">Marie-France Penet</name><affiliation><nlm:aff id="aff1">*Centre de Résonance Magnétique Biologique et Médicale, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6612,</nlm:aff></affiliation></author><author><name sortKey="Abou Hamdan, Mhamad" sort="Abou Hamdan, Mhamad" uniqKey="Abou Hamdan M" first="Mhamad" last="Abou-Hamdan">Mhamad Abou-Hamdan</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Coltel, Nicolas" sort="Coltel, Nicolas" uniqKey="Coltel N" first="Nicolas" last="Coltel">Nicolas Coltel</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Unité des Rickettsies et des Pathogènes émergents, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6020, Université de la Méditerranée, 13005 Marseille, France</nlm:aff></affiliation></author><author><name sortKey="Cornille, Emilie" sort="Cornille, Emilie" uniqKey="Cornille E" first="Emilie" last="Cornille">Emilie Cornille</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Grau, Georges E" sort="Grau, Georges E" uniqKey="Grau G" first="Georges E." last="Grau">Georges E. Grau</name><affiliation><nlm:aff id="aff4">Vascular Immunology Unit, Department of Pathology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney NSW 2402, Australia</nlm:aff></affiliation></author><author><name sortKey="De Reggi, Max" sort="De Reggi, Max" uniqKey="De Reggi M" first="Max" last="De Reggi">Max De Reggi</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author><author><name sortKey="Gharib, Bouchra" sort="Gharib, Bouchra" uniqKey="Gharib B" first="Bouchra" last="Gharib">Bouchra Gharib</name><affiliation><nlm:aff wicri:cut=", and" id="aff2">Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in <italic>Plasmodium berghei</italic> ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood–brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation–coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18195363</article-id><article-id pub-id-type="pmc">2234136</article-id><article-id pub-id-type="publisher-id">9076</article-id><article-id pub-id-type="doi">10.1073/pnas.0706867105</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Medical Sciences</subject></subj-group></subj-group></article-categories><title-group><article-title>Protection against cerebral malaria by the low-molecular-weight thiol pantethine</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Penet</surname><given-names>Marie-France</given-names></name><xref ref-type="aff" rid="aff1">*</xref></contrib><contrib contrib-type="author"><name><surname>Abou-Hamdan</surname><given-names>Mhamad</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Coltel</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cornille</surname><given-names>Emilie</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Grau</surname><given-names>Georges E.</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>de Reggi</surname><given-names>Max</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Gharib</surname><given-names>Bouchra</given-names></name><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="corresp" rid="cor1"><sup>¶</sup></xref></contrib><aff id="aff1">*Centre de Résonance Magnétique Biologique et Médicale, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6612,</aff><aff id="aff2"><sup>†</sup>Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6184, and</aff><aff id="aff3"><sup>‡</sup>Unité des Rickettsies et des Pathogènes émergents, Unite Mixte de Recherche Centre National de la Recherche Scientifique 6020, Université de la Méditerranée, 13005 Marseille, France; and</aff><aff id="aff4"><sup>§</sup>Vascular Immunology Unit, Department of Pathology, Faculty of Medicine and Bosch Institute, University of Sydney, Sydney NSW 2402, Australia</aff></contrib-group><author-notes><corresp id="cor1"><sup>¶</sup>To whom correspondence should be addressed. E-mail: <email>bouchra.gharib@univmed.fr</email></corresp><fn fn-type="edited-by"><p>Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved December 6, 2007</p></fn><fn fn-type="con"><p>Author contributions: M-F.P. and M.A-H. contributed equally to this work; M.-F.P., M.A.-H., N.C., E.C., and B.G. performed research; G.E.G., M.d.R., and B.G. designed research; G.E.G. contributed new reagents/analytic tools; M.d.R. and B.G. analyzed data; and M.d.R. and B.G. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>29</day><month>1</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>14</day><month>1</month><year>2008</year></pub-date><volume>105</volume><issue>4</issue><fpage>1321</fpage><lpage>1326</lpage><history><date date-type="received"><day>23</day><month>7</month><year>2007</year></date></history><copyright-statement>© 2008 by The National Academy of Sciences of the USA</copyright-statement><copyright-year>2008</copyright-year><license license-type="open-access"><p>Freely available online through the PNAS open access option.</p></license><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq00408001321.pdf"></self-uri><abstract><p>We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in <italic>Plasmodium berghei</italic> ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood–brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation–coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted.</p></abstract><kwd-group><kwd>blood–brain barrier</kwd><kwd>phosphatidylserine</kwd><kwd><italic>Plasmodium</italic></kwd><kwd>platelet activation</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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