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Cell-death mechanisms associated to metabolic stress in Trypanosoma cruzi and Trypanosoma brucei

Grant number: 14/03997-9
Support type:Research Grants - Visiting Researcher Grant - International
Duration: August 08, 2014 - September 05, 2014
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Ariel Mariano Silber
Grantee:Ariel Mariano Silber
Visiting researcher: Michael Duszenko
Visiting researcher institution: University of Tübingen, Germany
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Trypanosoma cruzi is the causative agent of Chagas disease, this pathogen depends on varied amino acids and carbohydrates as carbon sources. Besides, amino acids seem to participate in other pivotal biological processes along the whole life cycle of the parasite. In most organisms L-histidine has been shown to exhibit numerous biological functions, such as those related to the defense against the oxidative stress, generation of metabolic intermediates via the conversion of its carbon chain into glutamate, its regulatory properties in maintaining the intracellular levels of Cu2+ or Ni2+ by establishing coordination bonds, etc. However, little is known about the biological role of histidine in tripanosomatids. This proposal is part of a already initiated collaboration between Dr. Silber and Dra. Nowicki from Buenos Aires University, Argentina. Particularly, the main achievement of this proposal is to combine the experiences of both laboratories in order to gain knowledge regarding the potential roles that histidine might play in the processes related to oxidative stress defense. To accomplish this aim, T. cruzi epimastigotes will be exposed to oxidative stress in presence and absence of L-histidine, and the activities of key enzymes involved in maintaining the intracellular redox equilibrium will be comparatively measured in cell-free extracts, particularly those related to NADPH production and sulfur-containing amino acids metabolism will be determined. Moreover, the expression levels of those enzymes which display altered specific activities will be analyzed by Western-blot by utilizing specific antibodies. Finally, also the intracellular levels of biological relevant low molecular mass thiols will be comparatively analyzed. (AU)

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