Abstract
Trypanosoma cruzi infection in humans and experimental animals causes Chagas disease which is often accompanied by myocarditis, cardiomyopathy, and vasculopathy. T. cruzi-derived thromboxane A2 (TXA2) modulates vasculopathy and other pathophysiological features of Chagasic cardiomyopathy. Here, we provide evidence that epimastigotes, trypomastigotes, and amastigotes of T. cruzi (Brazil and Tulahuen strains) express a biologically active prostanoid receptor (PR) that is responsive to TXA2 mimetics, e.g. IBOP. This putative receptor, TcPR, is mainly localized in the flagellar membrane of the parasites and shows a similar glycosylation pattern to that of bona fide thromboxane prostanoid (TP) receptors obtained from human platelets. Furthermore, TXA2-PR signal transduction activates T. cruzi-specific MAPK pathways. While mammalian TP is a G-protein coupled receptor (GPCR); T. cruzi genome sequencing has not demonstrated any confirmed GPCRs in these parasites. Based on this genome sequencing it is likely that TcPR is unique in these protists with no counterpart in mammals. TXA2 is a potent vasoconstrictor which contributes to the pathogenesis of Chagasic cardiovascular disease. It may, however, also control parasite differentiation and proliferation in the infected host allowing the infection to progress to a chronic state.
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Abbreviations
- Tc :
-
T. cruzi
- TXA2 :
-
Thromboxane A2
- TXA2S:
-
TXA2 synthase
- TP:
-
Thromboxane prostanoid receptor
- IBOP/U46619:
-
TXA2 mimetics
- GPCR:
-
G-protein coupled receptor
- ERK:
-
Extracellular signal-regulated kinase
- MAPK:
-
Mitogen-activated protein kinase
- AA:
-
Arachidonic acid
- LOX:
-
Lipoxygenase
- COX:
-
Cyclooxygenase
- Cyt P450:
-
Cytochrome P450
- PR:
-
Prostanoid receptor
- AhR:
-
Aryl hydrocarbon receptor
- PLA2:
-
Phospholipase A2
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Acknowledgments
This work was supported by Scientist Development Grant from the National affiliate of the American Heart Association (SDG0735252N to S.M.), NIH grants AI-076248 ( H.B.T.), AI-058893 (HH), FAPEMIG, and CNPq (F.S.M.) and the National Health and Medical Research Council of Australia (AWA [512154]). We acknowledge the assistance Vickie Braunstein for cell culture and maintenance.
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The authors have declared that no competing interests exist.
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Mukherjee, S., Sadekar, N., Ashton, A.W. et al. Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi . Parasitol Res 112, 1417–1425 (2013). https://doi.org/10.1007/s00436-012-3271-5
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DOI: https://doi.org/10.1007/s00436-012-3271-5