Disarray of sarcomeric alpha-actinin in cardiomyocytes infected by Trypanosoma cruzi.
Infection with Trypanosoma cruzi causes acute myocarditis and chronic cardiomyopathy. Remarkable changes have been demonstrated in the structure and physiology of cardiomyocytes during infection by this parasite that may contribute to the cardiac dysfunction observed in Chagas' disease. We have investigated the expression of alpha-actinin, an actin-binding protein that plays a key role in the formation and maintenance of Z-lines, during the T. cruzi-cardiomyocyte interaction in vitro. Immunolocalization of alpha-actinin in control cardiomyocytes demonstrated a typical periodicity in the Z line of cardiac myofibrils, as well as its distribution at focal adhesion sites and along the cell-cell junctions. No significant changes were observed in the localization of alpha-actinin after 24 h of infection. In contrast, depletion of sarcomeric distribution of alpha-actinin occurred after 72 h in T. cruzi-infected cardiomyocytes, while no change occurred at focal adhesion contacts. Biochemical assays demonstrated a reduction of 46% and 32% in the expression of alpha-actinin after 24 h and 72 h of infection, respectively. Intracellular parasites were also stained with an anti-alpha-actinin antibody that recognized a protein of 78 kDa by Western blot. Taken together, our data demonstrate a degeneration of the myofibrils in cardiomyocytes induced by T. cruzi infection, rather than a disassembly of the I bands within sarcomeres.
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Laboratório de Ultra-Estrutura Celular, Departamento de Ultra-Estrutura e Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil.
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D000185:Actinin / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000473:pathology*; D004195:Disease Models, Animal; D006321:Heart / Q000469:parasitology; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000469:parasitology* / Q000648:ultrastructure*; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
D000185:Actinin