title: Identification of a functional prostanoid-like receptor in the protozoan parasite, Trypanosoma cruzi.
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.
authors: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA. sankar.mukhopadhyay@einstein.yu.edu
authors: Shankar
authors: S
authors: Mukherjee
authors: Nikaeta
authors: N
authors: Sadekar
authors: Anthony W
authors: AW
authors: Ashton
authors: Huan
authors: H
authors: Huang
authors: David C
authors: DC
authors: Spray
authors: Michael P
authors: MP
authors: Lisanti
authors: Fabiana S
authors: FS
authors: Machado
authors: Louis M
authors: LM
authors: Weiss
authors: Herbert B
authors: HB
authors: Tanowitz
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D005407:Flagella / Q000737:chemistry; D006031:Glycosylation; D011453:Prostaglandins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011982:Receptors, Prostaglandin / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics*
chemical_list: D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D013928:Thromboxane A2
references: Cardiovasc Pathol. 2000 Sep-Oct;9(5):257-65
references: 11064272
references: Braz J Med Biol Res. 1992;25(8):795-803
references: 1342611
references: FASEB J. 2000 Jan;14(1):6-16
references: 10627275
references: Adv Exp Med Biol. 2003;525:71-3
references: 12751739
references: Mol Pharmacol. 2002 Apr;61(4):817-31
references: 11901221
references: Cell Signal. 2005 Nov;17(11):1373-83
references: 15893915
references: Infect Immun. 2005 Apr;73(4):2496-503
references: 15784596
references: Comp Biochem Physiol C Comp Pharmacol Toxicol. 1987;87(1):5-8
references: 2885140
references: Cell Cycle. 2011 Oct 15;10(20):3519-26
references: 22030559
references: Annu Rev Pharmacol Toxicol. 2004;44:43-66
references: 14744238
references: Mediators Inflamm. 2004 Aug;13(4):235-40
references: 15545053
references: Nihon Yakurigaku Zasshi. 2004 Jan;123(1):34-40
references: 14695456
references: Nature. 1992 Dec 17;360(6405):684-6
references: 1465133
references: Biochem Biophys Res Commun. 2010 May 21;396(1):135-9
references: 20494126
references: J Clin Invest. 1987 Apr;79(4):1269-75
references: 3031135
references: Mol Biochem Parasitol. 2001 Jan 15;112(1):19-28
references: 11166383
references: Circulation. 2004 Nov 23;110(21):3360-6
references: 15545522
references: Am J Trop Med Hyg. 1990 Sep;43(3):274-81
references: 2121055
references: J Pharmacol Exp Ther. 1998 Aug;286(2):1026-36
references: 9694965
references: J Biol Chem. 1995 Jul 21;270(29):17551-8
references: 7615561
references: Cardiol Rev. 2012 Mar-Apr;20(2):53-65
references: 22293860
references: Biochem J. 1984 Jun 1;220(2):345-60
references: 6146314
references: J Biol Chem. 1993 Mar 25;268(9):6654-61
references: 8454637
references: Parasitology. 2007 Apr;134(Pt 4):491-502
references: 17121684
references: Tropenmed Parasitol. 1981 Dec;32(4):215-20
references: 7345684
references: Int J Biochem Cell Biol. 2008;40(12):2707-19
references: 18562239
references: PLoS One. 2011 Feb 15;6(2):e16959
references: 21347238
references: Mol Biochem Parasitol. 1982 May;5(5):309-19
references: 7099206
references: Arch Biochem Biophys. 1998 Apr 15;352(2):207-13
references: 9587408
references: Experientia. 1988 Feb 15;44(2):97-100
references: 3278926
references: Int Rev Cell Mol Biol. 2008;269:151-282
references: 18779059
references: Adv Parasitol. 2011;76:1-31
references: 21884885
references: Am J Trop Med Hyg. 1985 Mar;34(2):246-53
references: 3985268
references: Biochemistry. 1999 Jun 8;38(23):7594-600
references: 10360957
references: J Exp Med. 2007 Apr 16;204(4):929-40
references: 17420269
references: J Enzyme Inhib. 2001 Nov;16(5):433-41
references: 11916149
references: J Exp Med. 2002 Nov 4;196(9):1241-51
references: 12417633
references: Adv Parasitol. 2011;75:325-44
references: 21820563
references: Nature. 2000 Jan 13;403(6766):199-203
references: 10646605
references: Aging (Albany NY). 2010 Sep;2(9):597-611
references: 20844314
references: Cell Res. 2002 Mar;12(1):9-18
references: 11942415
references: J Eukaryot Microbiol. 1997 Mar-Apr;44(2):155-6
references: 9109262
references: Nature. 1992 Dec 17;360(6405):686-9
references: 1465134
references: Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):123-34
references: 12895595
references: Infect Immun. 2006 Oct;74(10):5522-8
references: 16988227
references: J Biol Chem. 1995 Jul 14;270(28):16576-9
references: 7542649
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3047-52
references: 14970333
references: Mol Biochem Parasitol. 1984 Apr;11:283-92
references: 6205265
references: Proc Natl Acad Sci U S A. 1983 Oct;80(20):6390-4
references: 6413976
references: Curr Opin Lipidol. 2009 Oct;20(5):402-8
references: 19741338
references: Int J Parasitol. 2003 Feb;33(2):221-8
references: 12633659
references: Aging (Albany NY). 2010 Oct;2(10):632-3
references: 21076180
references: Clin Immunol Immunopathol. 1996 Nov;81(2):122-8
references: 8906742
references: Clin Microbiol Rev. 1992 Oct;5(4):400-19
references: 1423218
references: PLoS Negl Trop Dis. 2010 May 18;4(5):e688
references: 20502520
references: Eur J Immunol. 2005 Jun;35(6):1849-58
references: 15864778
references: Int J Parasitol. 2001 May 1;31(5-6):499-511
references: 11334935
references: Science. 2000 Mar 17;287(5460):1960-4
references: 10720314
references: J Parasitol. 1996 Feb;82(1):124-30
references: 8627481
references: J Biol Chem. 2008 Mar 28;283(13):8065-9
references: 18250160
references: Biochim Biophys Acta. 2007 Aug;1773(8):1150-60
references: 17229475
references: J Pharmacol Exp Ther. 2001 Feb;296(2):426-33
references: 11160627
references: PLoS Negl Trop Dis. 2010 Aug 31;4(8):
references: 20824217
references: Cell Cycle. 2010 Dec 1;9(23):4650-5
references: 21084841
references: Endothelium. 1999;6(3):217-30
references: 10365773