Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease

摘要: Acetylation of lysine is a major posttranslational modification proteins and catalyzed by acetyltransferases, while deacetylases remove acetyl groups. Among the deacetylases, sirtuins are NAD(+)-dependent enzymes, which modulate gene silencing, DNA damage repair, several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting proliferation tumor cells, in this study, we investigated role these growth differentiation Trypanosoma cruzi, agent Chagas disease. We found that use salermide during parasite infection prevented initial multiplication after mammalian cell invasion T. cruzi at concentrations did not affect host viability. In addition, vivo was partially controlled upon administration salermide. There two TcSir2rp1 TcSir2rp3. By using specific antibodies lines overexpressing tagged versions localized cytosol TcSir2rp3 mitochondrion. overexpression acts to impair differentiation, whereas wild-type version an enzyme mutated active site improves both. The effects observed with were fully reverted adding salermide, inhibited expressed Escherichia coli 50% inhibitory concentration (IC50) ± standard error 1 0.5 μM. concluded sirtuin targeting could be used disease chemotherapy.