Thiosemicarbazones and organotelluranes are well-known compounds that have the ability to oxidize protein thiol groups. Changes in these groups interfere with various mitochondrial and cellular processes. Isolated mitochondria and cell cultures are ideal biological models for these studies. In this thesis we evaluated the action of thiosemicarbazones and tellurium compounds in the bioenergetics of isolated mitochondria in cultured cells and in mitochondrial proteome. The thiosemicarbazones TSC-H, TSC-I, TSC-F,-Cl TSC and TSC-NO2 induced apoptosis in K562 cells. TSC-NO2 seems to be able to chelate iron and induce cell death through a different mechanism and additionally has low toxicity to PBMN cells. The tellurium compound RVF19 was capable of oxidize thiol groups, deplete GSH content, decrease mitochondrial RCR and cause the opening of the PTP regulated by CsA. The compounds of tellurium RT-03 and RT-07B caused loss of mitochondrial membrane potential of MLAC cells. The organotelluranes RT-03, RT-04, RT-07B and RVF19 are able to induce the opening of the mitochondrial permeability transition pore that is resulting of proteic agglomeration caused by oxidative attack of these compounds. The analysis of this cluster-protein revealed the presence of ATP synthase subunits a and b, demonstrating that the PTP is probably formed by dimerization of the ATP synthase. Finally, the protocol of two-dimensional electrophoresis (2D-DIGE) was established and the technique of REDOX-DIGE for the samples labeled by fluorescent probes Cy3 and Cy5 in thiol groups.
News published in Agência FAPESP Newsletter about the scholarship: