Redox metabolism in Trypanosoma cruzi. Biochemical characterization of dithiol glutaredoxin dependent cellular pathways

MARQUEZ VANINA E; ARIAS DIEGO G.; CHIRIBAO MARIA L.; FARAL PAULA; CARLOS ROBELLO; IGLESIAS ALBERTO A.; GUERRERO S.A

BIOCHIMIE

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2014 vol. 106 p. 56 - 67

0300-9084

In Trypanosoma cruzi, the modification of thiols by glutathionylationedeglutathionylation and its potentialrelation to protective, regulatory or signaling functions have been scarcely explored. Herein wecharacterize a dithiolic glutaredoxin (TcrGrx), a redox protein with deglutathionylating activity, havingpotential functionality to control intracellular homeostasis of protein and non-protein thiols. The catalyticmechanism followed by TcrGrx was found dependent on thiol concentration. Results suggest thatTcrGrx operates as a dithiolic or a monothiolic Grx, depending on GSH concentration. TcrGrx functionalityto mediate reduction of protein and non-protein disulfides was studied. TcrGrx showed a preference forglutathionylated substrates respect to protein disulfides. From in vivo assays involving TcrGrx overexpressingparasites, we observed the contribution of the protein to increase the general resistanceagainst oxidative damage and intracellular replication of the amastigote stage. Also, studies performedwith epimastigotes overexpressing TcrGrx strongly suggest the involvement of the protein in a cellularpathway connecting an apoptotic stimulus and apoptotic-like cell death. Novel information is presentedabout the participation of this glutaredoxin not only in redox metabolism but also in redox signalingpathways in T. cruzi. The influence of TcrGrx in several parasite physiological processes suggests novelinsights about the protein involvement in redox signaling.