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Title: | Trypanosoma cruzi antigen that interacts with the beta1-adrenergic receptor and modifies myocardial contractile activity | Authors: | Joensen, Lilian G Borda, Enri Kohout, Trudy Perry, Stephen J Garcia, Gabriela Sterin-Borda, Leonor |
Keywords: | Trypanosoma cruzi;Enfermedad de Chagas | Issue Date: | 3-Apr-2003 | Publisher: | Elsevier | Journal: | Molecular and biochemical parasitology | Abstract: | Previously, we have demonstrated that plasma membranes from the parasite Trypanosoma cruzi (T. cruzi) recognize and adhere to host cells through parasite surface attachment molecules that have affinity for beta(1)-adrenergic receptors (beta(1)-ARs) on target organs. In this report we identify a parasite protein that not only interacts with beta(1)-ARs, but also displays beta-agonist-like activity. We demonstrate that a recombinant maltose binding protein fusion of Tc13 Tul (MBP-Tc13 Tul), a member of the T. cruzi antigen 13 family of surface antigen proteins, competes for binding sites with the beta-adrenergic receptor antagonist [125I]-CYP on membranes purified both from CHO cells expressing human beta(1)-ARs and from rat atria. The competition is prevented by pre-treating MBP-Tc13 Tul with antibodies directed against the EPKSA repeat domain of Tc13 Tul, implicating this portion of the molecule in binding to the beta(1)-AR. Furthermore, MBP-Tc13 Tul activates rat myocardial beta(1)-ARs, resulting in synthesis of cyclic adenosine monophosphate (cAMP) and an increase in cardiac contractility. These biological effects are selectively suppressed by the beta(1)-AR antagonist atenolol, by a synthetic peptide corresponding to the second extracellular loop of the human beta(1)-AR, and by the anti-EPKSA repeat antibodies. These results imply that the Tc13 Tul cell-surface antigen of T. cruzi plays a central role in misregulating the beta(1)-AR following parasite infection, and may be a causative factor of dysautonomic syndrome described in Chagas' disease. |
Description: | Fil: Joensen, Lilian. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina. Fil: Borda, Enri. Pharmacology Unit, School of Dentistry, Argentine National Research Council (CONICET), University of Buenos Aires, Buenos Aires; Argentina. Fil: Kohout, Trudy. Department of Medicine, Duke University Medical Center, Durham, NC; Estados Unidos. Fil: Perry, Stephen. Pharmacology Unit, School of Dentistry, Argentine National Research Council (CONICET), University of Buenos Aires, Buenos Aires; Argentina. Fil: García, Gabriela. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina. Fil: Sterin-Borda, Leonor. Pharmacology Unit, School of Dentistry, Argentine National Research Council (CONICET), University of Buenos Aires, Buenos Aires; Argentina. |
URI: | http://sgc.anlis.gob.ar/handle/123456789/2105 | ISSN: | 0166-6851 | DOI: | 10.1016/s0166-6851(03)00003-3 | Rights: | Closed Access |
Appears in Collections: | Publicaciones INP |
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