(42) THE THIOL-SPECIFIC ANTIOXIDANT ENZYME PREVENTS MITOCHONDRIAL PERMEABILITY TRANSITION

A.J. Kowaltowski (1), L.E.S. Netto (2) and A.E. Vercesi (1)
(1) Departamento de Patologia Clnica, Faculdade de Cincias Mdicas, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil
(2) Departamento de Bioqumica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil

Mitochondrial swelling and membrane protein thiol oxidation associated with mitochondrial permeability transition induced by Ca2+ and inorganic phosphate are inhibited in a dose-dependent manner either by catalase, the thiol-specific antioxidant enzyme (TSA), a protein recently demonstrated to present thiol peroxidase activity, or ebselen, a selenium-containing heterocycle which also possesses thiol peroxidase activity. This inhibition of mitochondrial permeability transition is due to the removal of mitochondrial-generated H2O2, which can easily diffuse to the extramitochondrial space. While ebselen required the presence of reduced glutathione as a reductant to grant its protective effect, TSA was fully reduced by mitochondrial components. Decrease in the oxygen concentration of the reaction medium also inhibits mitochondrial permeabilization and membrane protein thiol oxidation, in a concentration-dependent manner. The results presented in this report confirm that mitochondrial permeability transition induced by Ca2+ and inorganic phosphate is reactive oxygen species-dependent. TSA is a thiol peroxidase from a family of proteins widely distributed in mammalian tissues, which may present an important function as intracellular antioxidants, avoiding the onset of mitochondrial permeability transition, release of cytochrome c and consequent cell death.