Troglitazone induces differentiation in Trypanosoma brucei

Journal Article · Tue May 15 04:00:00 EDT 2007 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2007.03.003· OSTI ID:20972155

Denninger, Viola ^[1]; Figarella, Katherine ^[1]; Schoenfeld, Caroline ^[1]; Brems, Stefanie ^[2]; Busold, Christian ^[2]; Lang, Florian ^[3]; Hoheisel, Joerg ^[2]; Duszenko, Michael ^[1]

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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)

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.

• OSTI ID: 20972155
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 9 Vol. 313; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GENE REGULATION
GLOSSINA
GLYCOPROTEINS
METABOLISM
MICROSCOPY
MITOCHONDRIA
MORPHOLOGICAL CHANGES
RECEPTORS
TRYPANOSOMA
TRYPANOSOMES
VECTORS