Functional and biochemical characterization of a dithiol glutaredoxin in Trypanosoma cruzi.

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

Simposio; International Symposium - Thiol metabolism and redox regulation of cellular functions.; 2011

Trypanosoma cruzi is the causative agent of Chagas’ disease. Similar to that found for other aerobic parasites, T. cruzi is exposed to several reactive oxygen species, which are highly toxic for the parasite. These chemical species are generated both during the host defense reaction and also as byproducts of the aerobic metabolism. The metabolic pathways used by this organism to cope with such environmental changes and redox homeostasis are matter of our work. Glutaredoxins are ubiquitous oxidoreductases that play an important role in the control of cellular function. Despite a putative dithiol glutaredoxin (TcGrx) is encoded in the genome of T. cruzi, it was not yet characterized. In this work we present the cloning, expression and functional characterization of recombinant TcGrx. The protein was able to catalyze the reduction of oxidized glutathione and glutathionylated compounds using trypanothione as electron donor, demonstrating the functional relevance of this enzyme for the parasite. We present experimental assays (western blotting and enzymatic activity) that strongly support the occurrence of a dithiol glutaredoxin in T. cruzi epimastigote, being necessary to consider this protein as a new molecular component of the redox metabolism in trypanosomatids.