TY - JOUR
T1 - Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi
AU - Mukherjee, Shankar
AU - Sadekar, Nikaeta
AU - Ashton, Anthony W.
AU - Huang, Huan
AU - Spray, David C.
AU - Lisanti, Michael P.
AU - MacHado, Fabiana S.
AU - Weiss, Louis M.
AU - Tanowitz, Herbert B.
N1 - Funding Information:
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.
PY - 2013/4
Y1 - 2013/4
N2 - 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.
AB - 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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U2 - 10.1007/s00436-012-3271-5
DO - 10.1007/s00436-012-3271-5
M3 - Article
C2 - 23403991
AN - SCOPUS:84876409116
SN - 0932-0113
VL - 112
SP - 1417
EP - 1425
JO - Parasitology research
JF - Parasitology research
IS - 4
ER -
