The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi
Copyright © 2014 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:139 |
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| Enthalten in: |
Experimental parasitology - 139(2014) vom: 05. Apr., Seite 49-57 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Melo, Tatiana G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.05.2014 Date Revised 09.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.exppara.2014.02.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM235976970 |
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| 245 | 1 | 4 | |a The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi |
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| 500 | |a Date Revised 09.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2014 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cardiomyocytes | |
| 650 | 4 | |a FAK | |
| 650 | 4 | |a Invasion | |
| 650 | 4 | |a Signaling pathway | |
| 650 | 4 | |a Trypanosoma cruzi | |
| 650 | 4 | |a c-Src | |
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| 700 | 1 | |a Tucci, Amanda R |e verfasserin |4 aut | |
| 700 | 1 | |a Nogueira, Alanderson R |e verfasserin |4 aut | |
| 700 | 1 | |a Meirelles, Maria de Nazareth S L |e verfasserin |4 aut | |
| 700 | 1 | |a Pereira, Mirian C S |e verfasserin |4 aut | |
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