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Published on: September 30, 2017
Trypanosoma cruzi modulates the expression of Rabs and alters the endocytosis in mouse cardiomyocytes in vitro
Denise G J Batista1, Cristiane F Silva, Renata A Mota
1Departamento Ultra-estrutura e Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brasil.
Insights
Trypanosoma cruzi infection alters cardiomyocyte function by downregulating Rab7 and Rab11 proteins, impacting nutrient uptake. This study investigates Rab GTPase expression in Chagas disease pathogenesis.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Chagas disease, caused by Trypanosoma cruzi, is an incurable parasitic illness.
- Cardiomyocytes are key targets in T. cruzi infections, exhibiting altered physiology.
- Rab GTPases are crucial regulators of membrane traffic and cellular events.
Purpose of the Study:
- To characterize the expression of Rab proteins in T. cruzi-infected cardiomyocytes.
- To understand the role of Rab GTPases in the pathophysiology of Chagas disease in cardiac cells.
Main Methods:
- Analysis of Rab protein expression (Rab5a, Rab7, Rab11) in infected cardiomyocytes.
- Assessment of early endosome antigen 1 levels.
- Measurement of fluid phase ligand uptake in cardiac cultures.
Main Results:
- Downregulation of Rab7 and Rab11 expression was observed in infected cardiomyocytes.
- Rab5a expression remained stable, but early endosome antigen 1 was partially downregulated.
- Parasite infection led to decreased fluid phase ligand uptake by cardiac cells.
Conclusions:
- Altered Rab GTPase expression contributes to cardiomyocyte dysfunction in Chagas disease.
- Modulation of nutrient uptake and endocytic pathways impacts host cell physiology.
- Targeting Rab proteins may offer therapeutic strategies for Chagas disease complications.
Abstract:
Chagas disease is an incurable illness caused by the protozoan Trypanosoma cruzi. Cardiomyocytes represent important targets for the parasite infection and alterations in their physiology were reported. Because endocytosis is involved in different cellular events and guanosine triphosphatase (GTPase) Rab proteins play important roles in various aspects of the membrane traffic, our aim was to characterize the expression of Rab proteins in T. cruzi-infected cardiomyocytes, which displayed a downregulation of Rab7 and Rab11, whereas the expression of Rab5a was maintained in the infected cultures even after longer periods of parasite internalization, but early endosome antigen 1 was partially downregulated. The parasite infection also decreased the uptake of fluid phase ligands by the cardiac cultures. The regulation of GTPase proteins and effector molecules can contribute to the altered physiology of the host cells by modifying the normal incoming of nutrients as well as interfering with other important events related to the endocytic pathway.
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