Denninger Viola, Figarella Katherine, Schönfeld Caroline, Brems Stefanie, Busold Christian, Lang Florian, Hoheisel Jörg, Duszenko Michael
Interfakultäres Institut für Biochemie, Universität Tübingen, Hoppe-Seyler-Str. 4, D-72076 Tübingen, Germany.
Exp Cell Res. 2007 May 15;313(9):1805-19. doi: 10.1016/j.yexcr.2007.03.003. Epub 2007 Mar 15.
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.
布氏锥虫是一种导致昏睡病的原生动物寄生虫，通过采采蝇传播，经历复杂的生命周期，包括在昆虫媒介及其哺乳动物宿主内的几个特定阶段。在哺乳动物宿主中，从长细形态到短粗形态的分化是由一种未知的锥虫来源因子诱导的。在此我们描述一些噻唑烷二酮也能够诱导分化。在高等真核生物中，噻唑烷二酮主要通过与细胞内受体过氧化物酶体增殖物激活受体γ结合而参与代谢和分化过程。我们的研究聚焦于曲格列酮对血液期锥虫的影响。使用线粒体标记物（膜电位、琥珀酸脱氢酶活性、氰化钾对氧气摄取的抑制、细胞色素转录本的量）、形态变化（透射电子显微镜和光学显微镜）以及转化实验（可变表面糖蛋白外衣的丧失和二氢硫辛酰胺脱氢酶活性的增加）来监测分化。为了进一步研究导致这些变化的机制，进行了微阵列分析，结果显示表达位点相关基因8（ESAG8）上调，ESAG8是一种潜在的分化调节因子。
