A central role for free heme in the pathogenesis of severe malaria: the missing link?
Malaria, the disease caused by Plasmodium infection, is endemic to poverty in so-called underdeveloped countries. Plasmodium falciparum , the main infectious Plasmodium species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrom...
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| Veröffentlicht in: | Journal of molecular medicine (Berlin, Germany) Germany), 2008-10, Vol.86 (10), p.1097-1111 |
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| creator | Ferreira, Ana Balla, József Jeney, Viktória Balla, György Soares, Miguel P. |
| description | Malaria, the disease caused by
Plasmodium
infection, is endemic to poverty in so-called underdeveloped countries.
Plasmodium falciparum
, the main infectious
Plasmodium
species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrome that claims the lives of more than one million children ( |
| doi_str_mv | 10.1007/s00109-008-0368-5 |
| format | Article |
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Plasmodium
infection, is endemic to poverty in so-called underdeveloped countries.
Plasmodium falciparum
, the main infectious
Plasmodium
species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrome that claims the lives of more than one million children (<5 years old) per year. Attempts to eradicate
Plasmodium
infection, and in particular its lethal outcomes, have so far been unsuccessful. Using well-established rodent models of malaria infection, we found that survival of a
Plasmodium
-infected host is strictly dependent on the host’s ability to up-regulate the expression of heme oxygenase-1 (HO-1 encoded by the gene
Hmox1
). HO-1 is a stress-responsive enzyme that catabolizes free heme into biliverdin, via a reaction that releases Fe and generates the gas carbon monoxide (CO). Generation of CO through heme catabolism by HO-1 prevents the onset of cerebral malaria. The protective effect of CO is mediated via its binding to cell-free hemoglobin (Hb) released from infected red blood cells during the blood stage of
Plasmodium
infection. Binding of CO to cell-free Hb prevents heme release and thus generation of free heme, which we found to play a central role in the pathogenesis of cerebral malaria. We will address hereby how defense mechanisms that prevent the deleterious effects of free heme, including the expression of HO-1, impact on the pathologic outcome of
Plasmodium
infection and how these may be used therapeutically to suppress its lethal outcomes.</description><identifier>ISSN: 0946-2716</identifier><identifier>EISSN: 1432-1440</identifier><identifier>DOI: 10.1007/s00109-008-0368-5</identifier><identifier>PMID: 18641963</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Carbon Monoxide - metabolism ; Disease Models, Animal ; General aspects ; Heme - metabolism ; Heme - physiology ; Heme Oxygenase-1 - metabolism ; Hemoglobins - metabolism ; Human Genetics ; Human protozoal diseases ; Humans ; Infectious diseases ; Internal Medicine ; Malaria ; Malaria - enzymology ; Malaria - metabolism ; Malaria - physiopathology ; Malaria, Cerebral - enzymology ; Malaria, Cerebral - metabolism ; Malaria, Cerebral - physiopathology ; Medical sciences ; Models, Biological ; Molecular Medicine ; Parasitic diseases ; Plasmodium falciparum ; Protozoal diseases ; Review</subject><ispartof>Journal of molecular medicine (Berlin, Germany), 2008-10, Vol.86 (10), p.1097-1111</ispartof><rights>The Author(s) 2008</rights><rights>2008 INIST-CNRS</rights><rights>Springer-Verlag 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-c728ef79b4dd155fb547f38517326a586f3ebf32a765fac0e7a276cde0516b3b3</citedby><cites>FETCH-LOGICAL-c539t-c728ef79b4dd155fb547f38517326a586f3ebf32a765fac0e7a276cde0516b3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00109-008-0368-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00109-008-0368-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20719745$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18641963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ferreira, Ana</creatorcontrib><creatorcontrib>Balla, József</creatorcontrib><creatorcontrib>Jeney, Viktória</creatorcontrib><creatorcontrib>Balla, György</creatorcontrib><creatorcontrib>Soares, Miguel P.</creatorcontrib><title>A central role for free heme in the pathogenesis of severe malaria: the missing link?</title><title>Journal of molecular medicine (Berlin, Germany)</title><addtitle>J Mol Med</addtitle><addtitle>J Mol Med (Berl)</addtitle><description>Malaria, the disease caused by
Plasmodium
infection, is endemic to poverty in so-called underdeveloped countries.
Plasmodium falciparum
, the main infectious
Plasmodium
species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrome that claims the lives of more than one million children (<5 years old) per year. Attempts to eradicate
Plasmodium
infection, and in particular its lethal outcomes, have so far been unsuccessful. Using well-established rodent models of malaria infection, we found that survival of a
Plasmodium
-infected host is strictly dependent on the host’s ability to up-regulate the expression of heme oxygenase-1 (HO-1 encoded by the gene
Hmox1
). HO-1 is a stress-responsive enzyme that catabolizes free heme into biliverdin, via a reaction that releases Fe and generates the gas carbon monoxide (CO). Generation of CO through heme catabolism by HO-1 prevents the onset of cerebral malaria. The protective effect of CO is mediated via its binding to cell-free hemoglobin (Hb) released from infected red blood cells during the blood stage of
Plasmodium
infection. Binding of CO to cell-free Hb prevents heme release and thus generation of free heme, which we found to play a central role in the pathogenesis of cerebral malaria. We will address hereby how defense mechanisms that prevent the deleterious effects of free heme, including the expression of HO-1, impact on the pathologic outcome of
Plasmodium
infection and how these may be used therapeutically to suppress its lethal outcomes.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carbon Monoxide - metabolism</subject><subject>Disease Models, Animal</subject><subject>General aspects</subject><subject>Heme - metabolism</subject><subject>Heme - physiology</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hemoglobins - metabolism</subject><subject>Human Genetics</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Internal Medicine</subject><subject>Malaria</subject><subject>Malaria - enzymology</subject><subject>Malaria - metabolism</subject><subject>Malaria - physiopathology</subject><subject>Malaria, Cerebral - enzymology</subject><subject>Malaria, Cerebral - metabolism</subject><subject>Malaria, Cerebral - physiopathology</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>Molecular Medicine</subject><subject>Parasitic diseases</subject><subject>Plasmodium falciparum</subject><subject>Protozoal diseases</subject><subject>Review</subject><issn>0946-2716</issn><issn>1432-1440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kMtKxDAUhoMoOl4ewI0EQXfV3NO4ERFvILjRdUgzJzPVNh2TjuDb2zqDguDqLM53_vPzIXRIyRklRJ9nQigxBSFlQbgqC7mBJlRwVlAhyCaaECNUwTRVO2g359eB1tKIbbRDSyWoUXyCXq6wh9gn1-DUNYBDl3BIAHgOLeA64n4OeOH6eTeDCLnOuAs4wwckwK1rXKrdxTfT1jnXcYabOr5d7qOt4JoMB-u5h15ub56v74vHp7uH66vHwktu-sJrVkLQphLTKZUyVFLowEtJNWfKyVIFDlXgzGklg_MEtGNa-SkQSVXFK76HTle5i9S9LyH3dqjhoWlchG6ZLTVaaM7VAB7_AV-7ZYpDN8uoVqWRRg4QXUE-dTknCHaR6talT0uJHYXblXA7CLejcDveHK2Dl1UL09-LteEBOFkDLnvXhOSir_MPx4geS45BbMXlYRVnkH4b_v_9C_9UluQ</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>Ferreira, Ana</creator><creator>Balla, József</creator><creator>Jeney, Viktória</creator><creator>Balla, György</creator><creator>Soares, Miguel P.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>M7N</scope></search><sort><creationdate>20081001</creationdate><title>A central role for free heme in the pathogenesis of severe malaria: the missing link?</title><author>Ferreira, Ana ; 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Plasmodium
infection, is endemic to poverty in so-called underdeveloped countries.
Plasmodium falciparum
, the main infectious
Plasmodium
species in sub-Saharan countries, can trigger the development of severe malaria, including cerebral malaria, a neurological syndrome that claims the lives of more than one million children (<5 years old) per year. Attempts to eradicate
Plasmodium
infection, and in particular its lethal outcomes, have so far been unsuccessful. Using well-established rodent models of malaria infection, we found that survival of a
Plasmodium
-infected host is strictly dependent on the host’s ability to up-regulate the expression of heme oxygenase-1 (HO-1 encoded by the gene
Hmox1
). HO-1 is a stress-responsive enzyme that catabolizes free heme into biliverdin, via a reaction that releases Fe and generates the gas carbon monoxide (CO). Generation of CO through heme catabolism by HO-1 prevents the onset of cerebral malaria. The protective effect of CO is mediated via its binding to cell-free hemoglobin (Hb) released from infected red blood cells during the blood stage of
Plasmodium
infection. Binding of CO to cell-free Hb prevents heme release and thus generation of free heme, which we found to play a central role in the pathogenesis of cerebral malaria. We will address hereby how defense mechanisms that prevent the deleterious effects of free heme, including the expression of HO-1, impact on the pathologic outcome of
Plasmodium
infection and how these may be used therapeutically to suppress its lethal outcomes.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>18641963</pmid><doi>10.1007/s00109-008-0368-5</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of molecular medicine (Berlin, Germany), 2008-10, Vol.86 (10), p.1097-1111 |
| issn | 0946-2716 1432-1440 |
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| subjects | Animals Biological and medical sciences Biomedical and Life Sciences Biomedicine Carbon Monoxide - metabolism Disease Models, Animal General aspects Heme - metabolism Heme - physiology Heme Oxygenase-1 - metabolism Hemoglobins - metabolism Human Genetics Human protozoal diseases Humans Infectious diseases Internal Medicine Malaria Malaria - enzymology Malaria - metabolism Malaria - physiopathology Malaria, Cerebral - enzymology Malaria, Cerebral - metabolism Malaria, Cerebral - physiopathology Medical sciences Models, Biological Molecular Medicine Parasitic diseases Plasmodium falciparum Protozoal diseases Review |
| title | A central role for free heme in the pathogenesis of severe malaria: the missing link? |
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