Trypanosoma cruzi, the causative agent of
Chagas disease, is a
public health concern in
Latin America.
Epigenetic events, such as
histone acetylation,
affect DNA topology, replication and
gene expression.
Histone deacetylases (HDACs) are involved in
chromatin compaction and
post-translational modifications of cytoplasmic
proteins, such as
tubulin.
HDAC inhibitors, like trichostatin A (TSA), inhibit tumour
cell proliferation and promotes ultrastructural modifications. In the present study, TSA effects on
cell proliferation,
viability, cell cycle and
ultrastructure were evaluated, as well as on
histone acetylation and
tubulin expression of the T. cruzi epimastigote form. Protozoa proliferation and viability were reduced
after treatment with TSA. Quantitative proteomic analyses revealed an increase in
histone acetylation after 72 h of TSA
treatment. Surprisingly, results obtained by different
microscopy methodologies indicate that TSA does not
affect chromatin compaction, but alters
microtubule cytoskeleton dynamics and impair
kDNA segregation, generating polynucleated
cells with atypical morphology. Confocal
fluorescence microscopy and
flow cytometry assays indicated that treated
cell microtubules were more intensely acetylated. Increases in
tubulin acetylation may be directly related to the higher number of
parasites in the G2/
M phase after TSA
treatment. Taken together, these results suggest that deacetylase inhibitors represent excellent tools for
understanding trypanosomatid
cell biology.