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Title: Troglitazone induces differentiation in Trypanosoma brucei

Abstract

Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor {gamma}. Our studies focus on the effects of troglitazone on bloodstream form trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator.

Authors:
 [1];  [1];  [1];  [2];  [2];  [3];  [2];  [4]
  1. Interfakultaeres Institut fuer Biochemie, Universitaet Tuebingen, Hoppe-Seyler-Str. 4, D-72076 Tuebingen (Germany)
  2. Functional Genome Analysis, DKFZ, D-69120 Heidelberg (Germany)
  3. Institut fuer Physiologie, Gmelinstr. 5, D-72076 Tuebingen (Germany)
  4. Interfakultaeres Institut fuer Biochemie, Universitaet Tuebingen, Hoppe-Seyler-Str. 4, D-72076 Tuebingen (Germany). E-mail: michael.duszenko@uni-tuebingen.de
Publication Date:
OSTI Identifier:
20972155
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 9; Other Information: DOI: 10.1016/j.yexcr.2007.03.003; PII: S0014-4827(07)00115-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GENE REGULATION; GLOSSINA; GLYCOPROTEINS; METABOLISM; MICROSCOPY; MITOCHONDRIA; MORPHOLOGICAL CHANGES; RECEPTORS; TRYPANOSOMA; TRYPANOSOMES; VECTORS

Citation Formats

Denninger, Viola, Figarella, Katherine, Schoenfeld, Caroline, Brems, Stefanie, Busold, Christian, Lang, Florian, Hoheisel, Joerg, and Duszenko, Michael. Troglitazone induces differentiation in Trypanosoma brucei. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2007.03.003.
Denninger, Viola, Figarella, Katherine, Schoenfeld, Caroline, Brems, Stefanie, Busold, Christian, Lang, Florian, Hoheisel, Joerg, & Duszenko, Michael. Troglitazone induces differentiation in Trypanosoma brucei. United States. doi:10.1016/j.yexcr.2007.03.003.
Denninger, Viola, Figarella, Katherine, Schoenfeld, Caroline, Brems, Stefanie, Busold, Christian, Lang, Florian, Hoheisel, Joerg, and Duszenko, Michael. Tue . "Troglitazone induces differentiation in Trypanosoma brucei". United States. doi:10.1016/j.yexcr.2007.03.003.
@article{osti_20972155,
title = {Troglitazone induces differentiation in Trypanosoma brucei},
author = {Denninger, Viola and Figarella, Katherine and Schoenfeld, Caroline and Brems, Stefanie and Busold, Christian and Lang, Florian and Hoheisel, Joerg and Duszenko, Michael},
abstractNote = {Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor {gamma}. Our studies focus on the effects of troglitazone on bloodstream form trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator.},
doi = {10.1016/j.yexcr.2007.03.003},
journal = {Experimental Cell Research},
number = 9,
volume = 313,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2007},
month = {Tue May 15 00:00:00 EDT 2007}
}