ON THE FUNCTIONALITY OF A METHIONINE SULFOXIDE REDUCTASE B FROM Trypanosoma cruzi

ARIAS DG; CABEZA MS; ECHARREN ML; FARAL-TELLO P; IGLESIAS AA; ROBELLO C; GUERRERO SA

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2020

0891-5849

BackgroundMethionine is an amino acid susceptible to be oxidized to give a racemic mixture of Rand S forms of methionine sulfoxide (MetSO). This posttranslational modification hasbeen reported to occur in vivo under either normal or stress conditions. The reduction ofMetSO to methionine is catalyzed by methionine sulfoxide reductases (MSRs), thioldependent enzymes present in almost all organisms. These enzymes can reducespecifically one or another of the isomers of MetSO (free and protein-bound). Thisredox modification could change the structure and function of many proteins, eitherconcerned in redox or other metabolic pathways. The study of antioxidant systems inTrypanosoma cruzi has been mainly focused on the involvement of trypanothione, aspecific redox component for these organisms. Though, little information is availableconcerning mechanisms for repairing oxidized methionine residues in proteins, whichwould be relevant for the survival of these pathogens in the different stages of their lifecycle.MethodsWe report an in vitro functional and in vivo cellular characterization of methioninesulfoxide reductase B (MSRB, specific for protein-bound MetSO R-enantiomer) fromT. cruzi strain Dm28c.ResultsMSRB exhibited both cytosolic and mitochondrial localization in epimastigote cells.From assays involving parasites overexpressing MSRB, we observed the contribution ofthis protein to increase the general resistance against oxidative damage, the infectivityof trypomastigote cells, and intracellular replication of the amastigote stage. Also, wereport that epimastigotes overexpressing MSRB exhibit inhibition of themetacyclogenesis process; this suggesting the involvement of the proteins as negativemodulators in this cellular differentiation.Conclusions and General SignificanceThis report contributes to novel insights concerning redox metabolism in T. cruzi.Results herein presented support the importance of enzymatic steps involved in themetabolism of L-Met and in repairing oxidized macromolecules in this parasite.