The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi
| Autor: | Alanderson R. Nogueira, Tatiana G. Melo, Maria de Nazareth Meirelles, Mirian Claudia de Souza Pereira, Amanda R. Tucci |
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| Rok vydání: | 2014 |
| Předmět: |
Proteinase inhibitor
Trypanosoma cruzi Immunology c-Src Genistein Biology Quinolones CSK Tyrosine-Protein Kinase chemistry.chemical_compound Mice Invasion Protein-Tyrosine Kinases parasitic diseases Animals Myocytes Cardiac Sulfones Phosphorylation RNA Small Interfering Cardiomyocytes FAK Signaling pathway General Medicine biology.organism_classification Cell biology Infectious Diseases Pyrimidines src-Family Kinases chemistry Focal Adhesion Kinase 1 Gene Knockdown Techniques Pyrazoles Parasitology Signal transduction Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Experimental Parasitology. 139:49-57 |
| ISSN: | 0014-4894 |
| DOI: | 10.1016/j.exppara.2014.02.008 |
| Popis: | 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 μM PP1 (53% inhibition) and 40 μM 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. |
| Databáze: | OpenAIRE |
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