The parasite experiences an overall reduction on its energy metabolism

Several important Isosorbide enzymes of glycolysis were downregulated after gamma radiation exposure. Accordingly, the only enzyme from gluconeogenesis listed here was upregulated. Most enzymes involved in the amino acid metabolism were also downregulated, but shorter isoforms of the GluDH were upregulated after irradiation. They consist of three isoforms with experimental molecular weights lower than the predicted values, suggesting once again the Terbutaline Sulfate occurrence of posttranscriptional modifications/processing of important metabolic enzymes during the stress response. GluDH catalyzes the NADand/or NADP-dependent reversible deamination of L-glutamate to form alpha-ketoglutarate and is essential for the metabolism of amino nitrogen in organisms ranging from bacteria to mammals. T. cruzi has a metabolism that is largely based on the consumption of amino acids, mainly, proline, aspartate, and glutamate, which constitute the main carbon and energy sources of the epimastigote forms. In T. cruzi, GluDH has NADP-specific activity, indicating that it may serve as a pentose-phosphate shunt-independent source of NADPH in these parasites. Taken together, these results suggest that the parasite experiences an overall reduction on its energy metabolism as a consequence of its growth arrest after irradiation. We have identified four proteins classified as redox sensors in this study. While two of these are downregulated, the other two are upregulated and these are both tryparedoxins, which efficiently reduce hydrogen peroxide. Throughout its life cycle, T. cruzi is exposed to various stresses in different environments: the invertebrate and the vertebrate hosts. One of the most deleterious consequences of oxidative stress may be the formation of DNA lesions. Guanine is the most susceptible base to oxidation, due to its low redox potential, and the 7,8-dihydro-8-oxoguanine is the most common lesion. When 8-oxoG is inserted during DNA replication, it can generate double-strand breaks, which makes this lesion severely deleterious. Recently Aguiar et al., 2013, demonstrated that parasites overexpressin MutT are more resistant to the oxidative stress caused by hydrogen peroxide treatment.

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