Abstract
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. Whereas 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. The possible importance of TSA as an intracellular antioxidant, avoiding the onset of mitochondrial permeability transition, is discussed in the text.
Highlights
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 possesses thiol peroxidase activity
The results presented in this report confirm that mitochondrial permeability transition induced by Ca2؉ and inorganic phosphate is reactive oxygen species-dependent
The results presented in this paper were designed to investigate both if TSA is capable of inhibiting mitochondrial permeabilization associated with mitochondrial permeability transition (MPT) and if the inhibition of MPT by peroxidases is strictly related to their H2O2 removal activity
Summary
(Received for publication, December 29, 1997, and in revised form, March 11, 1998). From the ‡Departamento de Patologia Clınica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, 13083-970 Campinas, Sao Paulo, Brazil and §Departamento de Bioquımica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970 Campinas, Sao Paulo, 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 possesses thiol peroxidase activity. Many studies have proposed that MPT may be an initial step of apoptosis [15, 16] In this regard, Kroemer and co-authors [15] have recently demonstrated that mitochondrial swelling due to MPT leads to the release of a 50-kDa protein, the “apoptosis inducing factor,” from the intermembrane space into the cytosol. The effect of ebselen, a selenium-containing heterocycle and analogue of glutathione peroxidase, which presents peroxidase, but not free-radical scavenging activity [25], was studied
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
