Document Detail


Antiproliferative effect of dihydroxyacetone on Trypanosoma brucei bloodstream forms: cell cycle progression, subcellular alterations, and cell death.
MedLine Citation:
PMID:  17682096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated the effects of dihydroxyacetone (DHA) on Trypanosoma brucei bloodstream forms. DHA is considered an energy source for many different cell types. T. brucei takes up DHA readily due to the presence of aquaglyceroporins. However, the parasite is unable to use it as a carbon source because of the absence of DHA kinase (DHAK). We could not find a homolog of the relevant gene in the genomic database of T. brucei and have been unable to detect DHAK activity in cell lysates of the parasite, and the parasite died quickly if DHA was the sole energy source in the medium. In addition, during trypanosome cultivation, DHA induced growth inhibition with a 50% inhibitory concentration of about 1 mM, a concentration that is completely innocuous to mammals. DHA caused cell cycle arrest in the G(2)/M phase of up to 70% at a concentration of 2 mM. Also, DHA-treated parasites showed profound ultrastructural alterations, including an increase of vesicular structures within the cytosol and the presence of multivesicular bodies, myelin-like structures, and autophagy-like vacuoles, as well as a marked disorder of the characteristic mitochondrion structure. Based on the toxicity of DHA for trypanosomes compared with mammals, we consider DHA a starting point for a rational design of new trypanocidal drugs.
Authors:
Néstor L Uzcátegui; Didac Carmona-Gutiérrez; Viola Denninger; Caroline Schoenfeld; Florian Lang; Katherine Figarella; Michael Duszenko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-06
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  51     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-22     Completed Date:  2008-01-15     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3960-8     Citation Subset:  IM    
Affiliation:
Interfaculty Institute of Biochemistry, University of Tuebingen, Germany. uzcategn@ucv.ve
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / drug effects*
Cell Death / drug effects
Cell Survival / drug effects
Dihydroxyacetone / pharmacology*
Flow Cytometry
Membrane Potential, Mitochondrial / drug effects
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Reactive Oxygen Species / metabolism
Trypanocidal Agents / pharmacology*
Trypanosoma brucei brucei / drug effects*,  metabolism,  ultrastructure
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Trypanocidal Agents; 96-26-4/Dihydroxyacetone; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.29/glycerone kinase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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