Induction of the non-selective mitochondrial pore in lymphoid cells. 2. Intact rat thymocytes.
Increase of Ca2+ concentration in the cytosol of thymocytes to 400-600 nM causes slow accumulation of Ca2+ in mitochondria. Release of Ca2+ from mitochondria into the cytosol is induced by an uncoupler (FCCP) or by a dithiol cross-linking agent (phenylarsine oxide) and is inhibited by cyclosporin A--a specific inhibitor of the permeability transition pore in the inner mitochondrial membrane. In the presence of oxidizing agents (tert-butyl hydroperoxide and diamide), sub-optimal concentrations of uncoupler induce rapid cyclosporin-sensitive release of Ca2+. 6-Ketocholestanol, a recoupler under these conditions, causes redistribution of Ca2+ from the cytosol into mitochondria. These data indicate that partial uncoupling under conditions of oxidative stress causes opening of the permeability transition pore in a fraction of the mitochondria in intact lymphocytes. This mechanism mediates rapid release of Ca2+ from mitochondria into the cytosol.
Chernyak
B V
BV
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899, Russia. chernyak@pcman.genebee.msu.su
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010539:Permeability; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D001152:Arsenicals; D003432:Cross-Linking Reagents; C029341:oxophenylarsine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D016572:Cyclosporine; D020122:tert-Butylhydroperoxide; D002118:Calcium