Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes
BACKGROUND Cardiac physiology depends on coupling and electrical and mechanical coordination through the intercalated disc. Focal adhesions offer mechanical support and signal transduction events during heart contraction-relaxation processes. Talin links integrins to the actin cytoskeleton and serv...
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100343&lng=en&tlng=en |
| _version_ | 1827879823600517120 |
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| author | Tatiana G Melo Daniel Adesse Maria de Nazareth Meirelles Mirian Claudia S Pereira |
| author_facet | Tatiana G Melo Daniel Adesse Maria de Nazareth Meirelles Mirian Claudia S Pereira |
| author_sort | Tatiana G Melo |
| collection | DOAJ |
| description | BACKGROUND Cardiac physiology depends on coupling and electrical and mechanical coordination through the intercalated disc. Focal adhesions offer mechanical support and signal transduction events during heart contraction-relaxation processes. Talin links integrins to the actin cytoskeleton and serves as a scaffold for the recruitment of other proteins, such as paxillin in focal adhesion formation and regulation. Chagasic cardiomyopathy is caused by infection by Trypanosoma cruzi and is a debilitating condition comprising extensive fibrosis, inflammation, cardiac hypertrophy and electrical alterations that culminate in heart failure. OBJECTIVES Since mechanotransduction coordinates heart function, we evaluated the underlying mechanism implicated in the mechanical changes, focusing especially in mechanosensitive proteins and related signalling pathways during infection of cardiac cells by T. cruzi. METHODS We investigated the effect of T. cruzi infection on the expression and distribution of talin/paxillin and associated proteins in mouse cardiomyocytes in vitro by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). FINDINGS Talin and paxillin spatial distribution in T. cruzi-infected cardiomyocytes in vitro were altered associated with a downregulation of these proteins and mRNAs levels at 72 h post-infection (hpi). Additionally, we observed an increase in the activation of the focal adhesion kinase (FAK) concomitant with increase in β-1-integrin at 24 hpi. Finally, we detected a decrease in the activation of FAK at 72 hpi in T. cruzi-infected cultures. MAIN CONCLUSION The results suggest that these changes may contribute to the mechanotransduction disturbance evidenced in chagasic cardiomyopathy. |
| first_indexed | 2024-03-12T18:11:47Z |
| format | Article |
| id | doaj.art-e7f13d01ad3e493a9ec320a4cdd98727 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T18:11:47Z |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-e7f13d01ad3e493a9ec320a4cdd987272023-08-02T09:15:27ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-806011410.1590/0074-02760180593S0074-02762019000100343Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytesTatiana G MeloDaniel AdesseMaria de Nazareth MeirellesMirian Claudia S PereiraBACKGROUND Cardiac physiology depends on coupling and electrical and mechanical coordination through the intercalated disc. Focal adhesions offer mechanical support and signal transduction events during heart contraction-relaxation processes. Talin links integrins to the actin cytoskeleton and serves as a scaffold for the recruitment of other proteins, such as paxillin in focal adhesion formation and regulation. Chagasic cardiomyopathy is caused by infection by Trypanosoma cruzi and is a debilitating condition comprising extensive fibrosis, inflammation, cardiac hypertrophy and electrical alterations that culminate in heart failure. OBJECTIVES Since mechanotransduction coordinates heart function, we evaluated the underlying mechanism implicated in the mechanical changes, focusing especially in mechanosensitive proteins and related signalling pathways during infection of cardiac cells by T. cruzi. METHODS We investigated the effect of T. cruzi infection on the expression and distribution of talin/paxillin and associated proteins in mouse cardiomyocytes in vitro by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). FINDINGS Talin and paxillin spatial distribution in T. cruzi-infected cardiomyocytes in vitro were altered associated with a downregulation of these proteins and mRNAs levels at 72 h post-infection (hpi). Additionally, we observed an increase in the activation of the focal adhesion kinase (FAK) concomitant with increase in β-1-integrin at 24 hpi. Finally, we detected a decrease in the activation of FAK at 72 hpi in T. cruzi-infected cultures. MAIN CONCLUSION The results suggest that these changes may contribute to the mechanotransduction disturbance evidenced in chagasic cardiomyopathy.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100343&lng=en&tlng=encardiomyocytesTrypanosoma cruzifocal adhesiontalinpaxillinmechanotransduction |
| spellingShingle | Tatiana G Melo Daniel Adesse Maria de Nazareth Meirelles Mirian Claudia S Pereira Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes Memorias do Instituto Oswaldo Cruz cardiomyocytes Trypanosoma cruzi focal adhesion talin paxillin mechanotransduction |
| title | Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes |
| title_full | Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes |
| title_fullStr | Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes |
| title_full_unstemmed | Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes |
| title_short | Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes |
| title_sort | trypanosoma cruzi down regulates mechanosensitive proteins in cardiomyocytes |
| topic | cardiomyocytes Trypanosoma cruzi focal adhesion talin paxillin mechanotransduction |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100343&lng=en&tlng=en |
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