Biochemical characterization of thioredoxin dependent cellular pathways in Trypanosoma cruzi

NATALIA SASONI; PAULA FARAL-TELLO; MAGDALENA PORTELA; ROSARIO DURÁN; ADRIANA PARODI-TALICE; CARLOS ROBELLO; ALBERTO A. IGLESIAS; SERGIO A. GUERRERO; DIEGO G. ARIAS

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

The S-nitrosylationis a protein post-translational modification forming part of the cellularsignaling mechanisms. In this modification, the cysteine thiol is converted to nitrosothiolby the addition of a nitrosyl group. Several works have shown that thioredoxin(TRX) catalyzes the S-nitrosylationand denitrosylation of a large number of proteins. In Trypanosoma cruzi (the etiologic agent of Chagas disease), the modification ofthiol-proteins by S-nitrosylation andits potential relation to regulatory or signaling functions have not been exploredyet. Herein we present the functional properties of a TRX of T. cruzi (TcTRX), a redox protein with disulfide reductase activity, whichhave potential functionality to control redox intracellular homeostasis. Our in vitro data suggest that TcTRX operates as a redox mediator in trypanothione system. The nitrosylated TcTRX, presented a single ‑SNO group perTcTRX and it not brought aboutchanges in its disulfide reductase activity. In vivo assays, TcTRX overexpressing epimastigotespresented a slight increase in its tolerance to exogenous H2O2.In contrast, the overexpressingcells were more sensitive to exogenous GSNO. Complementarily,we evaluated the S-nitrosylatedprotein profiles by the biotin‑switch technique. TcTRX overexpressing epimastigotesshowed higher number of S‑nitrosylatedproteins than the non-overexpressing cells. These results suggest that TcTRX participate in proteinnitrosylation pathways in vivo. In parallel, TcTRX overexpressing cells showed increasedmetacyclogenic ability (of recombinant epimastigotes) and a rise in the mammaliancells infection capacity (of recombinant trypomastigotes). These resultsindicate that TcTRX participates inprocesses related to the infective capacity of this parasite. The influence of TcTRX in several parasite physiologicalprocesses suggests novel insights not only in redox metabolism but also inredox signaling pathways in T. cruzi.Granted byANPCyT (PICT2014-2103).