RESUMO
We have previously shown that Trypanosoma cruzi-infected cardiomyocytes present alterations in cytoskeletal organisation in vitro. The remarkable change in the host cell cytoskeleton opened up the question of whether treatment of infected cells with antitrypanosomal compounds, such as ergosterol biosynthesis inhibitors (EBIs), allows the reconstruction of myofibrils and the microtubule network, restoring the cell biological function. Therefore, 48-h-old T. cruzi-infected cardiomyocyte cultures were treated with 10 nM ketoconazole or posaconazole and cytoskeletal remodelling of the host cells was analysed by indirect immunofluorescence assay. Both compounds displayed a potent antiparasitic effect and dramatically reduced the infection ratio. After 120 h of treatment, actin polygonal configuration was frequently visualised in the host cell cytoplasm, suggesting the initial stage of actin framework restoration. Rearrangement of myofibrils and the microtubule network was achieved 168 h after the start of drug treatment. Our data demonstrate that the trypanocidal effect of EBIs lead to reconstruction of the cytoskeleton of T. cruzi-infected cardiomyocytes in vitro.
Assuntos
Citoesqueleto/efeitos dos fármacos , Ergosterol/biossíntese , Cetoconazol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Triazóis/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Citoesqueleto/química , Ergosterol/antagonistas & inibidores , Camundongos , Miócitos Cardíacos/química , Miofibrilas/efeitos dos fármacosRESUMO
The present paper summarizes new approaches regarding the progress done to the understanding of the interaction of Trypanosoma cruzi-cardiomyocytes. Mannose receptors localized at the surface of heart muscle cell are involved in binding and uptake of the parasite. One of the most striking events in the parasite-heart muscle cells interaction is the disruption of the actin cytoskeleton. We have investigated the regulation of the actin mRNA during the cytopathology induced in myocardial cells by the parasite. T. cruzi invasion increases calcium resting levels in cardiomyocytes. We have previously shown that Ca2+ ATPase of the sarcoplasmic reticulum (SERCA) is involved in the invasion of T. cruzi in cardiomyocytes. Treating the cells with thapsigargin, a drug that binds to all SERCA ATPases and causes depletion of intracellular calcium stores, we found a 75 per cent inhibition in the T. cruzi-cardiomyocytes invasion.