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

DIEGO G. ARIAS; MATÍAS S. CABEZA; MARÍA L. ECHARREN; PAULA FARAL-TELLO; ALBERTO A. IGLESIAS; CARLOS ROBELLO; SERGIO A. GUERRERO

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2020 vol. 158 p. 96 - 114

0891-5849

BackgroundMethionineis an amino acid susceptible to be oxidized to give a racemic mixture of R and S forms of methionine sulfoxide (MetSO). This posttranslationalmodification has been reported to occur invivo under either normal or stress conditions. The reduction of MetSO tomethionine is catalyzed by methionine sulfoxide reductases (MSRs),thiol-dependent enzymes present in almost all organisms. These enzymes canreduce specifically one or another of the isomers of MetSO (free andprotein-bound). This redox modification could change the structure and functionof many proteins, either concerned in redox or other metabolic pathways. Thestudy of antioxidant systems in Trypanosomacruzi has been mainly focused on the involvement of trypanothione, aspecific redox component for these organisms. Though, little information isavailable concerning mechanisms for repairing oxidized methionine residues inproteins, which would be relevant for the survival of these pathogens in thedifferent stages of their life cycle.MethodsWe report anin vitro functional and in vivo cellular characterization of methioninesulfoxide reductase B (MSRB, specific for protein-bound MetSO R-enantiomer) from T. cruzi strain Dm28c.ResultsMSRBexhibited both cytosolic and mitochondrial localization in epimastigote cells.From assays involving parasites overexpressing MSRB, we observed thecontribution of this protein to increase the general resistance againstoxidative damage, the infectivity of trypomastigote cells, and intracellularreplication of the amastigote stage. Also, we report that epimastigotesoverexpressing MSRB exhibit inhibition of the metacyclogenesis process; this suggestingthe involvement of the proteins as negative modulators in this cellulardifferentiation.Conclusionsand General SignificanceThis report contributes to novel insightsconcerning redox metabolism in T. cruzi.Results herein presented support the importance of enzymatic steps involved inthe metabolism of L‑Met and in repairing oxidized macromolecules in this parasite.