1. Troglitazone induces differentiation in Trypanosoma brucei.
- Author
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Denninger V, Figarella K, Schönfeld C, Brems S, Busold C, Lang F, Hoheisel J, and Duszenko M
- Subjects
- Animals, Biomarkers analysis, Biomarkers metabolism, Cell Differentiation physiology, Cell Respiration physiology, Cell Shape drug effects, Cell Shape physiology, Cytochromes genetics, Cytochromes metabolism, Energy Metabolism drug effects, Energy Metabolism physiology, Gene Expression Regulation physiology, Hypoglycemic Agents pharmacology, Membrane Glycoproteins metabolism, Membrane Potential, Mitochondrial drug effects, Membrane Potential, Mitochondrial physiology, Mitochondria metabolism, Oxygen Consumption drug effects, Oxygen Consumption physiology, Protozoan Proteins genetics, Succinate Dehydrogenase drug effects, Succinate Dehydrogenase metabolism, Troglitazone, Trypanosoma brucei brucei ultrastructure, Trypanosomiasis, African drug therapy, Up-Regulation genetics, Cell Differentiation drug effects, Cell Respiration drug effects, Chromans pharmacology, Mitochondria drug effects, Thiazolidinediones pharmacology, Trypanosoma brucei brucei drug effects, Trypanosoma brucei brucei metabolism
- 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.
- Published
- 2007
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