Functional and Biochemical characterization of a Dithiol Glutaredoxin in Trypanosoma cruzi

MARQUEZ VANINA E; ARIAS DIEGO G.; IGLESIAS ALBERTO A.; GUERRERO SERGIO A.

Casa Pueblo, Punta Ballena, Maldonado

Simposio; Thiol metabolism and redox regulation of cellular functions; 2011

UDELAR-IP Montevideo

Functional and Biochemical characterization of a Dithiol Glutaredoxin in Trypanosoma cruzi Márquez, Vanina1; Arias, Diego1; Iglesias, Alberto2; Guerrero, Sergio1.   1Laboratorio de Bioquímica Microbiana, 2 Laboratorio de Enzimología Molecular.  Facultad de Bioquímica y Ciencias Biológicas. Universidad Nacional del Litoral. Santa Fe, Argentina.     Trypanosoma cruzi,the causative agent of Chagas’ disease, is exposed to several reactive and highly toxic oxygen species (ROS), as consequence of host defense mechanisms and the incomplete reduction of O2 during aerobic metabolism. The metabolic pathways that T. cruzi use to cope with such environmental challenges and redox homeostasis are matter of our work. Glutaredoxins are oxidoreductases belonging to the family of thioredoxins that play an important role in the control of cellular function in several organisms. In this work, we summarized results about biochemical characterization and experiments performed in order to elucidate the possible roles played by a dithiol glutaredoxin (TcGrx) in T. cruzi. The biochemical characterization was performed in enzymatic systems standard for glutaredoxins. TcGrx was able to catalyze the reduction of oxidized glutathione and glutathionylaze compounds using trypanothione as electron donor. Western blotting assays strongly support the occurrence of a TcGrx in T. cruzi epimastigote. Cultures of T. cruzi over expressing TcGrx were subjected to oxidative stress by adding glucose oxidase in a glucose containing media. We evaluated cell viability and verified that TcGrx helps T. cruzi against the action of the oxidants agents generated. Considering these results, it is possible to suggest protective functions of TcGrx, a new molecular component of the redox metabolism in trypanosomatids, which is involved in glutathionylation or deglutathionylation of proteins and recycling of reduced glutathione instead of direct detoxification of reactive oxygen species.