Characterization of Histone deacetylase enzymes from cestode parasites as potential drug targets of Neglected Diseases

VACA, HUGO; CAMICIA, FEDERICO; MACCHIAROLI, NATALIA; CELENTANO, ANA M.; KAMENETZKY, LAURA; CUCHER, MARCELA; ROSENZVIT, MARA C.

Ciudad Autónoma de Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SOCIEDADES DE BIOCIENCIAS

Cestode parasites cause neglected diseases such as hydatidosis.These parasites have complex life cycles undergoing metamorphicevents that comprise cell proliferation, differentiation and death. Thissuggests the involvement of a complex system of gene expressioncontrol that has been associated with changes in chromatin structure in trematode parasites. Histone deacetylase enzymes (HDAC)remove acetyl groups from histones and other cellular effectors,thus directly influencing the chromatin structure and thereby regulatinggene transcription and other cellular processes. HDAC havebeen validated as drug targets for the treatment of cancer and otherdiseases including parasitic infections. However, knowledge ofHDAC in cestode parasites is lacking. Previously, we have shownthe presence and transcription of HDAC genes in several speciesof cestode parasites. In this work, we aimed to study the effect ofthe pan-HDAC inhibitor Trichostatin A (TSA) in Mesocestoides corti,a cestode laboratory model. We found a decrease in the viability,measured by AlamarBlue assay and motility index determination,and observed phenotypic alterations in M. corti larvae upon incubationwith TSA. To assess the molecular target of TSA, we evaluatedchanges in the total amount of acetylated histone H4 by western blotusing anti-acetylated histone H4 antibody. We observed a band correspondingto acetylated H4 histone in parasites treated with TSAbut not in control parasites, suggesting that TSA strongly inhibitsH4 histone deacetylation. This effect was not observed in parasitestreated with praziquantel and albendazole suggesting a specific effectof TSA. These findings suggest that HDAC could have an essentialrole in cestode development and survival. This work providesa first step into the study of epigenetic mechanisms in cestode parasitesand explores new alternatives to treat the diseases they cause.