CHARACTERIZATION OF HISTONE DEACETYLASE ENZYMES OF CESTODE PARASITES AS POTENTIAL DRUG TARGETS OF NEGLECTED DISEASES

VACA, H.; CAMICIA, F.; MACCHIAROLI, N.; CELENTANO, AM; KAMENETZKY, L.; ROSENZVIT, M. C.

Congreso; Reunión Conjunta de Sociedades de BioCiencias; 2017

Cestode parasites cause neglected diseasessuch as hydatidosis. These parasites have complex life cycles undergoingmetamorphic events that comprise cell proliferation, differentiation and death.This suggests the involvement of a complex system of gene expression controlthat has been associated with changes in chromatin structure in trematodeparasites. Histone deacetylase enzymes (HDAC) removeacetyl groups from histones and other cellular effectors, thus directlyinfluencing the chromatin structure and thereby regulating gene transcriptionand other cellular processes. HDAC have been validated as drug targets for thetreatment of cancer and other diseases including parasitic infections. However,knowledge if HDAC in cestode parasites is lacking. Previously, we have shownthe presence and expression of HDAC genes in 3 cestode parasites. In this work, we aimed to study the effect of thepan-HDAC inhibitor Trichostatin A (TSA) in Mesocestoidescorti, a cestode laboratory model. We found a decrease in the viability,measured by AlamarBlue assay and motility index determination, and observed phenotypicalterations in M. corti larvae when incubatedwith TSA. To assess the molecular target of TSA, we evaluated changes in the total amount ofacetylated histone H4 by western blot using anti-acetylated histone H4 antibody.We observed a band corresponding to acetylated H4 histone in parasites treatedwith TSA but not in control parasites, suggesting that TSA strongly inhibits H4histone deacetylation. This effect was not observed in parasites treated withpraziquantel and albendazole suggesting a specific effect ofTSA. These findings suggestthat HDAC could have an essential role in cestode development and survival. Thiswork provides a first step into the study of epigenetic mechanisms in cestode parasitesand explores new alternatives to treat the diseases they cause.