Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes.
Animals
Blotting, Western
Chagas Cardiomyopathy
/ metabolism
Fluorescent Antibody Technique, Indirect
Immunoblotting
Mechanotransduction, Cellular
/ physiology
Mice
Myocytes, Cardiac
/ parasitology
Paxillin
/ metabolism
Real-Time Polymerase Chain Reaction
Talin
/ metabolism
Trypanosoma cruzi
/ physiology
Journal
Memorias do Instituto Oswaldo Cruz
ISSN: 1678-8060
Titre abrégé: Mem Inst Oswaldo Cruz
Pays: Brazil
ID NLM: 7502619
Informations de publication
Date de publication:
2019
2019
Historique:
received:
17
12
2018
accepted:
08
07
2019
entrez:
22
8
2019
pubmed:
23
8
2019
medline:
5
9
2019
Statut:
ppublish
Résumé
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. 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. 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). 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. The results suggest that these changes may contribute to the mechanotransduction disturbance evidenced in chagasic cardiomyopathy.
Sections du résumé
BACKGROUND
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
OBJECTIVE
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
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
RESULTS
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
CONCLUSIONS
The results suggest that these changes may contribute to the mechanotransduction disturbance evidenced in chagasic cardiomyopathy.
Identifiants
pubmed: 31433004
pii: S0074-02762019000100343
doi: 10.1590/0074-02760180593
pmc: PMC6697411
pii:
doi:
Substances chimiques
Paxillin
0
Talin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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