Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-10-26
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-0329
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
560-4
pubmed:dateRevised
2011-11-17
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
pubmed:articleTitle
Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies.
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
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't