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

Shankar Mukherjee, Nikaeta Sadekar, Anthony W. Ashton, Huan Huang, David C. Spray, Michael P. Lisanti, Fabiana S. MacHado, Louis M. Weiss, Herbert B. Tanowitz

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1417-1425
Number of pages9
JournalParasitology Research
Volume112
Issue number4
DOIs
StatePublished - Apr 2013

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thromboxanes
Trypanosoma cruzi
prostaglandins
Prostaglandins
Protozoa
Parasites
Thromboxane A2
parasites
receptors
Cardiomyopathies
cardiomyopathy
Genome
Prostaglandin H2 Receptors Thromboxane A2
Thromboxane Receptors
Communicable Disease Control
Chagas Disease
epimastigotes
Thromboxanes
trypomastigotes
Myocarditis

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi. / Mukherjee, Shankar; Sadekar, Nikaeta; Ashton, Anthony W.; Huang, Huan; Spray, David C.; Lisanti, Michael P.; MacHado, Fabiana S.; Weiss, Louis M.; Tanowitz, Herbert B.

In: Parasitology Research, Vol. 112, No. 4, 04.2013, p. 1417-1425.

Research output: Contribution to journalArticle

Mukherjee, Shankar ; Sadekar, Nikaeta ; Ashton, Anthony W. ; Huang, Huan ; Spray, David C. ; Lisanti, Michael P. ; MacHado, Fabiana S. ; Weiss, Louis M. ; Tanowitz, Herbert B. / Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi. In: Parasitology Research. 2013 ; Vol. 112, No. 4. pp. 1417-1425.
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