Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10931
Title: The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi
Authors: Melo, Tatiana G
Tucci, Amanda R
Nogueira, Alanderson R
Meirelles, Maria de Nazareth S. L
Pereira, Mirian C. S
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ, Brasil.
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 25 lM PP1 (53% inhibition) and 40 lM 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 60 min), 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.
Keywords: FAK
c-Src
Tropanosoma cruzi
Cardiomyocytes
Invasion
Signaling pathway
DeCS: Trypanosoma cruzi
Miócitos Cardíacos
Doença de Chagas
Issue Date: 2014
Publisher: Elsevier
Citation: MELO, Tatiana G. et al. The involvement of FAK and Src in the invasion of cardiomyocites by Tripanosoma cruzi. Experimental Parasitology, v.139, p.49-57, 2014.
DOI: 10.1016/j.exppara.2014.02.008
ISSN: 0014-4894
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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