Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 169, Issue 1, Pages 50-54Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2009.09.001
Keywords
Trypanosomes; Glycolysis; RNA interference; Aldolase; Glyceraldehyde-3-phosphate dehydrogenase
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Funding
- Belgian 'Fonds de la Recherche Scientifique Medicale' (FRSM)
- Interuniversity Attraction Poles of the Belgian Federal Office for Scientific, Technical and Cultural Affairs
- European Commission [ICA4-CT-2001-10075]
- FONACIT (Venezuela) [C-1498-07-03-B]
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Aldolase (ALD) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Trypanosoma brucei are considered to be promising targets for chemotherapeutic treatment of African sleeping sickness, because glycolysis is the single source of ATP for the parasite when living in the human bloodstream. Moreover, these enzymes appeared to possess distinct kinetic and structural properties that have already been exploited for the discovery of effective and selective inhibitors with trypanocidal activity. Here we present an experimental, quantitative assessment of the importance of these enzymes for the glycolytic pathway. This was achieved by decreasing the concentrations of ALD and GAPDH by RNA interference. The effects of these knockdowns on parasite growth, levels of various enzymes and transcripts, enzyme activities and glucose consumption were studied. A partial depletion of ALD and GAPDH was already sufficient to rapidly kill the trypanosomes. An effect was also observed on the activity of some other glycolytic enzymes. (C) 2009 Elsevier B.V. All rights reserved.
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