Abstract
BackgroundChagas’ disease is caused by the protozoan Trypanosoma cruzi and affects thousands of people worldwide. The available treatments are unsatisfactory, and new drugs must be developed. Our group recently reported the trypanocidal activity of the synthetic compound N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (C4), but the mechanism of action of this compound was unclear.Methodology/Principal FindingsWe investigated the mechanism of action of C4 against epimastigote and trypomastigote forms of T. cruzi. The results showed alterations in mitochondrial membrane potential, alterations in cell membrane integrity, an increase in the formation of reactive oxygen species, phosphatidylserine exposure, a reduction of cell volume, DNA fragmentation, and the formation of lipid inclusions.Conclusion/SignificanceThese finding suggest that mitochondria are a target of C4, the dysfunction of which can lead to different pathways of cell death.
Highlights
Chagas’ disease is a tropical infection caused by Trypanosoma cruzi
Transmission electron microscopy indicated that the mitochondrion is the major organelle affected by this compound in trypanosomatids, such as T. cruzi and Leishmania amazonensis [6, 8]
We suggest that mitochondrial dysfunction induced by C4 can lead to different pathways of cell death in T. cruzi
Summary
Chagas’ disease is caused by the protozoan Trypanosoma cruziand affects thousands of people worldwide. Data Availability Statement: All relevant data are within the paper. The results showed alterations in mitochondrial membrane potential, alterations in cell membrane integrity, an increase in the formation of reactive oxygen species, phosphatidylserine exposure, a reduction of cell volume, DNA fragmentation, and the formation of lipid inclusions. These finding suggest that mitochondria are a target of C4, the dysfunction of which can lead to different pathways of cell death. June 18, 2015 β-Carboline Induced Mitochondrial Dysfuncion in Trypanosoma cruzi data collection and analysis, decision to publish, or preparation of the manuscript
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