Effects of organoteluranes in the oxidative stress, intra-cell calcium homeostase and in the expression of antioxidant enzymes: Studies in cells, isolated mitochondria and membrane models

• Grant number: 08/00030-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2008
• End date: June 30, 2012
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Iseli Lourenço Nantes Cardoso
• Grantee: Felipe Samuel Pessoto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Literatura data about organotelluranes reveals that these compounds have efficient antioxidant properties, as well as the ability to react with thiol group of proteins. In a previous work (Pessoto et al., Dissertação de Mestrado e Chem. Res. Toxicol., 2007, 20, 1453-1461), our research group analized the effect of organotelluranes, RT-03 e RT-04, in rat liver mitochondria. The effects on mitochondria were dependent of the tellurane concentration and varied from protection against lipid oxidation to opening of the Cyclosporin A and Ca2+- dependent and Ca2+-independent permeability transition pore (PTPM) opening. These effects were caused by chemical action, i.e., reactivity with thiol groups of proteins and by physical action, i.e., changes in the membrane fluidity. Considering that there is not concord in Literature regarding the specificity of the proteins that participate of the PTPM composition and the ATP/ADP translocator (ANT) is one the proteins postulated as a PTPM element, we intend to investigate the reactivity of telluranes with isolated ANT incorporated in liposomes and, by bidimensional electroforese as well as by mass spectrometry, to identify the mitochondrial proteins that react with telluranes. On the other hand, due to the efficient antioxidant action, telluranes did not induce oxidative stress in the mitochondrial lipids and matrix even after glutathione depletion, it is interesting to determine whether telluranes affect Ca2+ traffic in cells by microinjection and confocal microscopy analysis. Also regarding oxidative stress, it is interesting to investigate whether telluranes affect the expression of antioxidant enzymes such as SOD, catalase and glutathione peroxidase. The expression of the enzymes will be investigated by RT-PCR. Further, we intend to investigate the reaction mechanism of teluranes with biomolecules by using EPR/spin trapping technique.