Trypanosoma cruzi down-regulates mechanosensitive proteins in cardiomyocytes

• Published in: Memórias do Instituto Oswaldo Cruz Vol. 114; p. e180593
• Main Authors: Melo, Tatiana G, Adesse, Daniel, Meirelles, Maria de Nazareth, Pereira, Mirian Claudia S
• Format: Journal Article
• Language: English
• Published: Brazil Instituto Oswaldo Cruz, Ministério da Saúde 01.01.2019; Fundação Oswaldo Cruz (FIOCRUZ)
• Subjects: Animals; Blotting, Western; cardiomyocytes; Chagas Cardiomyopathy - metabolism; Fluorescent Antibody Technique, Indirect; focal adhesion; Immunoblotting; mechanotransduction; Mechanotransduction, Cellular - physiology; Mice; Myocytes, Cardiac - parasitology; Original; PARASITOLOGY; paxillin; Paxillin - metabolism; Real-Time Polymerase Chain Reaction; talin; Talin - metabolism; TROPICAL MEDICINE; Trypanosoma cruzi; Trypanosoma cruzi - physiology; cardiomyocytes; focal adhesion; paxillin; talin; mechanotransduction; Trypanosoma cruzi
• ISSN: 0074-0276; 1678-8060; 1678-8060
• DOI: 10.1590/0074-02760180593

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.