INVESTIGADORES
ANGEL Sergio Oscar
congresos y reuniones científicas
Título:
EFFECT OF THE ACTIVATION OF HISTONE DEACETYLATION BY SIR2 ON THE LYTIC CYCLE OF TOXOPLASMA GONDII
Autor/es:
CONTRERAS MS; CAMPO V; VANAGAS L; ANGEL SO
Lugar:
CABA
Reunión:
Congreso; Sociedad Argentina de Protozoología XXVII Reunión Anual; 2015
Institución organizadora:
Sociedad Argentina de Protozoología
Resumen:
The Telomeric Associated Sequences-Like (TAS-L) found in T. gondii are heterochromatic regions that would be associated with specific factors linked to epigenetic silencing mechanisms. One of the major mechanisms regulating the chromatin status is the acetylation and deacetylation of histone lysine residues at the N-terminal tail. Moreover, it is well-known that these regions are associated with histone deacetylases that promote the spreading of TAS-heterochromatin and TAS-associated gene regulation. The principal actor in this scenario is the histone deacetylase type III ?dependent of NAD+-Sir2. In T. gondii a putative Sir2 deacetylase has been identified but its function remains uncharacterized. Here, our goal is to investigate indirectly the function of chromatin deacetylation by Sir2 on replication of the parasite by using drugs. We tested the effects of two inhibitors Sirtinol and Nicotinamide and the activator, Resveratrol, on the sirtuins deacetylase activity. To evaluate the effect of these drugs in T. gondii growth, a plaque lysis assay was performed, we measured the lytic cycle of the tachyzoite in a period of 5 days. It was observed that inhibitors did not have significant effects on total lysed area in comparison with untreated. By contrast, tachyzoites under Resveratrol treatment presented a decrease in the size of the lysed area in a dose dependent manner, suggesting an interference with the lytic cycle. In addition, a replication assay in the same conditions was performed, and the number of parasites per parasitophorous vacuole was also counted. In the case of Resveratrol, it was observed a decrease in the number of parasites/vacuole. Moreover, aberrant vacuoles were observed compared with the control. At high doses of Resveratrol a high parasite mortality was observed. In conclusion, the Sir2 activator seems to interfere with DNA replication, remaining to establish the link between such replication phenotype and TAS-L maintenance.