Troglitazone induces differentiation in Trypanosoma brucei

Denninger, Viola; Figarella, Katherine; Schönfeld, Caroline; Brems, Stefanie; Busold, Christian; Läng, Florian; Hoheisel, Jöerg; Duszenko, Michael

doi:10.1016/j.yexcr.2007.03.003

Cited by 12 publications

(20 citation statements)

References 73 publications

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“…Therefore, the mitochondria of short stumpy trypanosomes are metabolically divergent from the mitochondria in long slender BSF T. brucei cells. These results are consistent with prior work (4,5,8,11). The functional changes might be a preadaptation that allows short stumpy BSF T. brucei to function in the intestines of infected tsetse flies and enables them to differentiate further into PCF trypanosomes.…”

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confidence: 92%

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Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

et al. 2009

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confidence: 92%

“…Differential gene expression and the formation of cristea in the inner mitochondrial membrane have been shown to occur during this transition (8,11,19). Furthermore, the trypanosomal homologue of complex I of the respiratory chain is expressed in short stumpy BSF trypanosomes (4,5,18).…”

mentioning

confidence: 99%

Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

et al. 2009

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“…Initially, we assayed the ability of the cell permeable cAMP analogues, pCPTcAMP (24), 8pCPT-2′- O -Me-cAMP (35) or troglitazone (36), to induce hallmarks of stumpy formation in monomorphic lines, namely the inhibition of cell growth and improved efficiency of differentiation to procyclic forms. These validation experiments were carried out using a monomorphic reporter line transfected with both the pHD617-CAT- PAD1 3′-UTR expression vector and pHD617-GUS-actin 3′-UTR (Figure 1A), enabling gene repression and alleviation via the PAD1 3′-UTR to be monitored in the context of a constitutively expressed Actin 3′-UTR control.…”

Section: Resultsmentioning

confidence: 99%

“…The reporter line was then exposed to 100 µM pCPTcAMP, 10 µM 8pCPT-2′- O -Me-cAMP or 5 µM troglitazone (36) doses being determined via titration experiments or literature analysis (data not shown). After treatment with each compound, the cells were investigated for different parameters of stumpy formation, including cell growth arrest (Figure 5A–C), their capacity for differentiation to procyclic forms (Figure 5J–L; Supplementary Figure S6) and their expression of the CAT (Figure 5D–F) and GUS (Figure 5G–I) reporter proteins.…”

Section: Resultsmentioning

confidence: 99%

Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei

MacGregor

Matthews

2012

Nucleic Acids Research

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Trypanosomatid parasites provide an extreme model for the posttranscriptional control of eukaryotic gene expression. However, most analysis of their differential gene regulation has focussed on comparisons between life-cycle stages that exist in the blood of mammalian hosts and tsetse flies, the parasite’s vector. These environments differ acutely in their temperature, and nutritional, metabolic and molecular composition. In the bloodstream, however, a more exquisitely regulated developmental step occurs: the production of transmissible stumpy forms from proliferative slender forms. This transition occurs in the relatively homogenous bloodstream environment, with stumpy-specific gene expression being repressed until accumulation of a proposed parasite-derived signal, stumpy induction factor. Here, we have dissected the regulatory signals that repress the expression of the stumpy-specific surface transporter PAD1 in slender forms. Using transgenic parasites capable of stumpy formation we show that PAD1-repression is mediated by its 3′-untranslated region. Dissection of this region in monomorphic slender forms and pleomorphic slender and stumpy forms has revealed that two regulatory regions co-operate to repress PAD1 expression, this being alleviated on exposure to SIF in pleomorphs or cAMP analogues that act as stumpy induction factor mimics in monomorphs. These studies identify elements that regulate trypanosome gene expression during development in their mammalian host.

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“…In S. mansoni, a small scale study identified genes such as glutathione S-transferase are upregulated in response to xenobiotics [34]. More recently, a microarray-based study of Trypanosoma brucei revealed that exposure to thiazolidinediones and the resultant cellular differentiation of the parasite can be attributed to an upregulation of the expression site associated gene 8 (ESAG8) [35]. Differential gene expression has also been demonstrated in Caenorhabditis elegans in relation to ivermectin resistance and increased levels of multidrug resistance proteins [36].…”

Section: Parasite Gene Expression Responses To Chemotherapymentioning

confidence: 99%

Better Understanding of Anti-Schistosomal Strategies Through Microarray Analysis

Gobert

2010

IDDT

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Schistosomiasis is a wide-spread parasitic disease of many tropical and sub-tropical countries. The current central control measure is the use of single drug praziquantel, although the mode of action is not fully realised and the possibility resistance is a concern. The preferred alternative control strategy would involve a target vaccine, which unfortunately hasn't yet been realised. A useful research tool for better understanding the immunological elimination of an active infection is vaccination with live, radiation attenuation parasites. Both of these important research approaches, whether defining the current drug regime or the immunological interactions between the host and parasite, can be better understood through the profiling of the transcriptional status of the parasite. This review will present some of the recent microarray based studies examining the Schistosoma parasite under chemotherapy or immunological stress. Finally some suggestions on how microarray analyses may better help to identify new detoxification or immuno-evasion mechanisms of the parasite and what subsequent functional validations will be needed to support transcriptional findings.

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Troglitazone induces differentiation in Trypanosoma brucei

Cited by 12 publications

References 73 publications

Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

Adaptations in the Glucose Metabolism of Procyclic Trypanosoma brucei Isolates from Tsetse Flies and during Differentiation of Bloodstream Forms

Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei

Better Understanding of Anti-Schistosomal Strategies Through Microarray Analysis

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