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Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi

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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.

Disclosure of potential conflicts of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA

    Shankar Mukherjee, Nikaeta Sadekar, Huan Huang, Louis M. Weiss & Herbert B. Tanowitz

  2. Department of Perinatal Research, Kolling Institute of Perinatal Medical Research, University of Sydney, Sydney, Australia

    Anthony W. Ashton

  3. Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA

    David C. Spray

  4. Manchester Breast Centre and Breakthrough Breast Cancer Research Unit, Paterson Institute for Cancer Research, School of Cancer, Enabling Science and Technology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK

    Michael P. Lisanti

  5. Department of Biochemistry and Immunology, Institute for Biological Sciences, and the Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Fabiana S. Machado

  6. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

    Louis M. Weiss & Herbert B. Tanowitz

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  1. Shankar Mukherjee
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  2. Nikaeta Sadekar
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  3. Anthony W. Ashton
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  4. Huan Huang
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  5. David C. Spray
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  6. Michael P. Lisanti
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  7. Fabiana S. Machado
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  8. Louis M. Weiss
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  9. Herbert B. Tanowitz
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Correspondence to Shankar Mukherjee or Herbert B. Tanowitz.

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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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