rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
|
pubmed:dateCreated |
2010-10-26
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pubmed:databankReference |
|
pubmed:abstractText |
Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to eliminate trypanosomes in human infective strain cultures.
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pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
1873-0329
|
pubmed:author |
pubmed-author:AkiyamaHiroshiH,
pubmed-author:FujiokaSunaoS,
pubmed-author:FukumotoShinyaS,
pubmed-author:HirataHaruyukiH,
pubmed-author:InoueNoboruN,
pubmed-author:KidoYasutoshiY,
pubmed-author:KitaKiyoshiK,
pubmed-author:NakamuraKosukeK,
pubmed-author:SaimotoHiroyukiH,
pubmed-author:SakamotoKimitoshiK,
pubmed-author:SuzukiTakashiT,
pubmed-author:WatanabeYoh-ichiY,
pubmed-author:YabuYoshisadaY
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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pubmed:issnType |
Electronic
|
pubmed:volume |
59
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
560-4
|
pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20688188-Amino Acid Sequence,
pubmed-meshheading:20688188-Animals,
pubmed-meshheading:20688188-Conserved Sequence,
pubmed-meshheading:20688188-Enzyme Inhibitors,
pubmed-meshheading:20688188-Humans,
pubmed-meshheading:20688188-Mitochondrial Proteins,
pubmed-meshheading:20688188-Molecular Sequence Data,
pubmed-meshheading:20688188-Oxidoreductases,
pubmed-meshheading:20688188-Parasitic Sensitivity Tests,
pubmed-meshheading:20688188-Plant Proteins,
pubmed-meshheading:20688188-Protozoan Proteins,
pubmed-meshheading:20688188-Sequence Alignment,
pubmed-meshheading:20688188-Sequence Analysis, DNA,
pubmed-meshheading:20688188-Sesquiterpenes,
pubmed-meshheading:20688188-Trypanosoma brucei brucei,
pubmed-meshheading:20688188-Trypanosoma brucei gambiense,
pubmed-meshheading:20688188-Trypanosoma brucei rhodesiense,
pubmed-meshheading:20688188-Trypanosomiasis, African
|
pubmed:year |
2010
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pubmed:articleTitle |
Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies.
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pubmed:affiliation |
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Tokyo 113-0033, Japan. kosnakamura@nihs.go.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|