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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1997-10-29
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pubmed:abstractText |
Malarial pigment (haemozoin; HZ) is generally considered to be a non-toxic, high-molecular-weight storage form of undigested, toxic, host-haemoglobin haem. The available information on HZ indicates that it is a very heterozygous material. Its exact structure, in terms of constituent proteins (remnants of host globin v. parasite proteins), the type of linkage between the haem moieties (mu-oxo haem dimers further aggregated by non-covalent hydrophobic bonds v. mutually independent haematin monomers), iron status in the haem (penta-co-ordinated, high-spin ferriprotoporphyrin IX v. esa-co-ordinated, low-spin ferriprotoporphyrin IX), and compositions (beta-haematin-like structure without functionally relevant proteins or other constituents v. a ferriprotoporphyrin-IX core with aggregated proteins and phospholipids of host and parasite origin) remains a subject of controversy. When investigated by macrophages, HZ is not inert but affects a number of functional parameters. Crude pigment, as present in infected erythrocytes and shed after schizont rupture, may be considered the 'natural diet' ingested by macrophages in infected blood. It is a powerful source of radicals that may generate lipoperoxides and derived, toxic hydroxyaldehydes such as 4-hydroxynonenal (HNE). High concentrations of HNE, which have been detected in HZ-fed macrophages, inhibit protein kinase C (PKC). Complexes between HNE and PKC have also been detected in immunoprecipitated PKC from HZ-fed macrophages. HNE-mediated inhibition of PKC (and of other, as yet unidentified enzymes and processes) may explain HZ-mediated effects. HZ-mediated inhibition of NADPH-oxidase, the enzyme responsible for oxidative bursts, may only be partially explained by PKC inhibition. As Hz-laden human and murine macrophages produce increased amounts of tumour necrosis factor-alpha, interleukins 1 and 6, and macrophage inflammatory proteins 1 alpha and 1 beta, HZ-macrophage interactions may contribute to the cytokine-mediated manifestations of malaria.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Hemeproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NADP,
http://linkedlifedata.com/resource/pubmed/chemical/Pigments, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/hemozoin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0003-4983
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
91
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
501-16
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pubmed:dateRevised |
2009-5-18
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pubmed:meshHeading |
pubmed-meshheading:9329987-Animals,
pubmed-meshheading:9329987-Hemeproteins,
pubmed-meshheading:9329987-Macrophages,
pubmed-meshheading:9329987-NADP,
pubmed-meshheading:9329987-Phagocytes,
pubmed-meshheading:9329987-Pigments, Biological,
pubmed-meshheading:9329987-Plasmodium falciparum,
pubmed-meshheading:9329987-Protein Kinase C,
pubmed-meshheading:9329987-Structure-Activity Relationship
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pubmed:year |
1997
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pubmed:articleTitle |
Malarial pigment (haemozoin): a very active 'inert' substance.
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pubmed:affiliation |
Department of Genetics, Biology and Medical Chemistry, University of Torino, Italy. arese@molinette.unito.it
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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