[Closure of Ca2+-dependent pores by cyclosporin A: the role of magnesium ions, adenine nucleotides, and conformation status of the ADP/ATP antiporter].
Effects of ADP and Mg2+ on the ability of cyclosporin A to "reseal" mitochondria permeabilized by Ca2+ and P(i) have been studied. Cyclosporin A was completely ineffective, when ADP and Mg2+ were not included into the incubation medium. Both ADP and Mg2+ used at high concentrations potentiated the effect of cyclosporin A and prevented it reversal by carboxyatractylate. Data on the influence of different concentrations of ADP and Mg2+ on the resealing efficiency of cyclosporin A suggest that the true effector modulating the state of the Ca(2+)-dependent pore is the ADP-Mg2+ complex, but not ADP or Mg2+ used separately. The ability of non-hydrolyzable analogs of adenine nucleotides, ADP-S and ATP-S, to potentiate the resealing action of cyclosporin on mitochondria permeabilized by loading of different Ca2+ concentrations to that of ADP was compared. ATP-S was ineffective when the pore was induced by high concentrations of Ca2+. The results obtained are discussed in terms of hypothesis on the direct involvement of the ADP/ATP antiporter in regulation of the inner mitochondrial membrane Ca(2+)-dependent pore state.
Andreev
A Iu
AIu
Mikhaĭlova
L M
LM
Starkov
A A
AA
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000378:metabolism*; D004347:Drug Interactions; D006868:Hydrolysis; D008274:Magnesium / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats
D000227:Adenine Nucleotides; D001278:Atractyloside; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases; D008274:Magnesium; C003853:carboxyatractyloside; D002118:Calcium
Zakrytie CA2+-zavisimoĭ pory tsiklosporinom A: rol' ionov magniia, adeninovykh nukleotidov i konformatsionnogo sostoianiia ADP/ATP-antiportera.