title: Trypanosoma cruzi antigen that interacts with the beta1-adrenergic receptor and modifies myocardial contractile activity.
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.
authors.affiliation: Argentine National Parasitology Institute "Dr. Mario Fatala Chaben", ANLIS "Dr. Carlos G. Malbrán", University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Lilian
authors.initials: L
authors.lastname: Joensen
authors.forename: Enri
authors.initials: E
authors.lastname: Borda
authors.forename: Trudy
authors.initials: T
authors.lastname: Kohout
authors.forename: Stephen
authors.initials: S
authors.lastname: Perry
authors.forename: Gabriela
authors.initials: G
authors.lastname: García
authors.forename: Leonor
authors.initials: L
authors.lastname: Sterin-Borda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism* / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D009124:Muscle Proteins; D018342:Receptors, Adrenergic, beta-1; D011994:Recombinant Proteins; D001262:Atenolol; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol