title: Redox metabolism in Trypanosoma cruzi. Biochemical characterization of dithiol glutaredoxin dependent cellular pathways.
abstract: In Trypanosoma cruzi, the modification of thiols by glutathionylation-deglutathionylation and its potential relation to protective, regulatory or signaling functions have been scarcely explored. Herein we characterize a dithiolic glutaredoxin (TcrGrx), a redox protein with deglutathionylating activity, having potential functionality to control intracellular homeostasis of protein and non-protein thiols. The catalytic mechanism followed by TcrGrx was found dependent on thiol concentration. Results suggest that TcrGrx operates as a dithiolic or a monothiolic Grx, depending on GSH concentration. TcrGrx functionality to mediate reduction of protein and non-protein disulfides was studied. TcrGrx showed a preference for glutathionylated substrates respect to protein disulfides. From in vivo assays involving TcrGrx overexpressing parasites, we observed the contribution of the protein to increase the general resistance against oxidative damage and intracellular replication of the amastigote stage. Also, studies performed with epimastigotes overexpressing TcrGrx strongly suggest the involvement of the protein in a cellular pathway connecting an apoptotic stimulus and apoptotic-like cell death. Novel information is presented about the participation of this glutaredoxin not only in redox metabolism but also in redox signaling pathways in T. cruzi. The influence of TcrGrx in several parasite physiological processes suggests novel insights about the protein involvement in redox signaling.
authors.affiliation: Instituto de Agrobiotecnología del Litoral, Facultad de Bioquímica y Ciencias Biológicas, CONICET-UNL, Santa Fe, Argentina.
authors.forename: Vanina E
authors.initials: VE
authors.lastname: Márquez
authors.affiliation: Instituto de Agrobiotecnología del Litoral, Facultad de Bioquímica y Ciencias Biológicas, CONICET-UNL, Santa Fe, Argentina.
authors.forename: Diego G
authors.initials: DG
authors.lastname: Arias
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Unidad de Biología Molecular, Institut Pasteur, Montevideo, Uruguay.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Chiribao
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur, Montevideo, Uruguay.
authors.forename: Paula
authors.initials: P
authors.lastname: Faral-Tello
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; Unidad de Biología Molecular, Institut Pasteur, Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robello
authors.affiliation: Instituto de Agrobiotecnología del Litoral, Facultad de Bioquímica y Ciencias Biológicas, CONICET-UNL, Santa Fe, Argentina.
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Iglesias
authors.affiliation: Instituto de Agrobiotecnología del Litoral, Facultad de Bioquímica y Ciencias Biológicas, CONICET-UNL, Santa Fe, Argentina. Electronic address: sguerrer@fbcb.unl.edu.ar.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Guerrero
mesh_terms: D017209:Apoptosis; D055162:Biocatalysis; D015153:Blotting, Western; D003600:Cytosol / Q000201:enzymology; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D018613:Microscopy, Confocal; D010084:Oxidation-Reduction; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014050:Toluene / Q000031:analogs & derivatives* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000166:cytology / Q000235:genetics / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; D007527:Isoenzymes; D008164:Luminescent Proteins; D015800:Protozoan Proteins; D014050:Toluene; D005978:Glutathione; C004848:dithiol
keywords: Deglutathionylation; Glutaredoxin; Redox metabolism; Thioltransferase; Trypanosoma