title: The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi.
abstract: The activation of signaling pathways involving protein tyrosine kinases (PTKs) has been demonstrated during Trypanosoma cruzi invasion. Herein, we describe the participation of FAK/Src in the invasion of cardiomyocytes by T. cruzi. The treatment of cardiomyocytes with genistein, a PTK inhibitor, significantly reduced T. cruzi invasion. Also, PP1, a potent Src-family protein inhibitor, and PF573228, a specific FAK inhibitor, also inhibited T. cruzi entry; maximal inhibition was achieved at concentrations of 25μM PP1 (53% inhibition) and 40μM PF573228 (50% inhibition). The suppression of FAK expression in siRNA-treated cells and tetracycline-uninduced Tet-FAK(WT)-46 cells significantly reduced T. cruzi invasion. The entry of T. cruzi is accompanied by changes in FAK and c-Src expression and phosphorylation. An enhancement of FAK activation occurs during the initial stages of T. cruzi-cardiomyocyte interaction (30 and 60min), with a concomitant increase in the level of c-Src expression and phosphorylation, suggesting that FAK/Src act as an integrated signaling pathway that coordinates parasite entry. These data provide novel insights into the signaling pathways that are involved in cardiomyocyte invasion by T. cruzi. A better understanding of the signal transduction networks involved in T. cruzi invasion may contribute to the development of more effective therapies for the treatment of Chagas' disease.
authors.affiliation: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Melo
authors.affiliation: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Tucci
authors.affiliation: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Alanderson R
authors.initials: AR
authors.lastname: Nogueira
authors.affiliation: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Maria de Nazareth S L
authors.initials: Mde N
authors.lastname: Meirelles
authors.affiliation: Laboratório de Ultra-estrutura Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil. Electronic address: mirian@ioc.fiocruz.br.
authors.forename: Mirian C S
authors.initials: MC
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D032383:Myocytes, Cardiac / Q000469:parasitology*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000502:physiology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; D011720:Pyrazoles; D011743:Pyrimidines; D015363:Quinolones; D034741:RNA, Small Interfering; D013450:Sulfones; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases
keywords: Cardiomyocytes; FAK; Invasion; Signaling pathway; Trypanosoma cruzi; c-Src