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Funcional caracterization and intracellular location of Trypanosoma cruzi mitochondrial and nuclear components of the antioxidant system dependent or not on trypanothione

Grant number: 11/20084-9
Support type:Regular Research Grants
Duration: February 01, 2012 - July 31, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal researcher:Fernanda Ramos Gadelha
Grantee:Fernanda Ramos Gadelha
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Among the proteins of the Trypanosoma cruzi antioxidant system, cytosolic and mitochondrial tryparedoxin peroxidase (TcMPx) that have an important role in parasite's virulence and viability. The cytosolic antioxidant system has been elucidated, but how the mitochondrial system dependent on TcMPx works is still unclear. Bioinformatics analysis, immulocalization and bioenergetics experiments performed by our group, suggest its location in the cytosol and in the mitochondrial membrane that would allow it to interact with the cytosolic antioxidant system. Additionally, a TcMPx larger band (approximately 28kDa) was detected being more expressed under oxidative stress conditions. Until now, the possibility of the existence of a nuclear antioxidant system has never been addressed. Our group identified a tryparedoxin (TcTPNII) in the perinuclear region, but with whom it interacts it is not known. This research proposal aim to determine TcMPx exact intracellular location, its interatome, possible migration in the cell under oxidative stress, specify which domain is facing the citosol and the sequence of the approximately 28kDa protein. Also, determine TcTPNII interatome and its intracellular localization in the different T. cruzi forms. In addition, the extension to which the mitochondrion contributes to parasite survival under H2O2 or genotoxic treatment will be covered. These results will provide valuable information regarding the strategies used by the parasite to detoxify hydroperoxides and allow the identification of new targets that could lead to the development of a more specific therapy. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DIAS, L.; PELOSO, E. F.; LEME, A. F. P.; CARNIELLI, C. M.; PEREIRA, C. N.; WERNECK, C. C.; GUERRERO, S.; GADELHA, F. R. Trypanosoma cruzi tryparedoxin II interacts with different peroxiredoxins under physiological and oxidative stress conditions. Experimental Parasitology, v. 184, p. 1-10, JAN 2018. Web of Science Citations: 1.
PELOSO, E. F.; DIAS, L.; QUEIROZ, R. M. L.; LEME, A. F. P. PAES; PEREIRA, C. N.; CARNIELLI, C. M.; WERNECK, C. C.; SOUSA, M. V.; RICART, C. A. O.; GADELHA, F. R. Trypanosoma cruzi mitochondrial tryparedoxin peroxidase is located throughout the cell and its pull down provides one step towards the understanding of its mechanism of action. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1864, n. 1, p. 1-10, JAN 2016. Web of Science Citations: 4.
AGUIAR, PEDRO H. N.; FURTADO, CAROLINA; REPOLES, BRUNO M.; RIBEIRO, GRAZIELLE A.; MENDES, ISABELA C.; PELOSO, EDUARDO F.; GADELHA, FERNANDA R.; MACEDO, ANDREA M.; FRANCO, GLORIA R.; PENA, SERGIO D. J.; TEIXEIRA, SANTUZA M. R.; VIEIRA, LEDA Q.; GUARNERI, ALESSANDRA A.; ANDRADE, LUCIANA O.; MACHADO, CARLOS R. Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability. PLoS Neglected Tropical Diseases, v. 7, n. 6 JUN 2013. Web of Science Citations: 23.

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