Cyclosporin A-sensitive permeability transition pore is involved in Cd(2+)-induced dysfunction of isolated rat liver mitochondria: doubts no more.
There is dose-dependent Cd(2+)-evoked swelling of isolated rat liver mitochondria energized by complex I, II, or IV respiratory substrates in sucrose medium in the absence of added Ca(2+) and P(i), which is prevented by Sr(2+). Permeability transition effectors (ADP, CsA, EGTA, RR, DTT, ATR, P(i), and Ca(2+)) affect in a corresponding way Cd(2+)-promoted membrane permeabilization in NH(4)NO(3), KCl, and sucrose media. Maximal depression of Cd(2+)-induced swelling is achieved by simultaneous addition of ADP, Mg(2+), and CsA that produces either synergistic (NH(4)NO(3)) or additive (KCl and sucrose media) action. Sustained activation by low [Cd(2+)] of mitochondrial basal respiration in KCl medium is observed both in the absence and in the presence of rotenone and/or oligomycin but only in the latter case (rotenone+oligomycin) CsA inhibits completely Cd(2+) activation of St 4 respiration and partially reverses DNP-uncoupled respiration depressed by cadmium. Cd(2+) effects are discussed in terms of comparison with those of Zn(2+) and PhAsO.
Belyaeva
Elena A
EA
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St. Petersburg, Russia. belyaeva@EB100330.spb.edu
Glazunov
Vadim V
VV
Korotkov
Sergey M
SM
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010539:Permeability; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D019802:Succinic Acid / Q000378:metabolism
C419345:6,10,14-trimethyl-2-pentadecanol; D005233:Fatty Alcohols; D008293:Malates; D002104:Cadmium; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; C030298:malic acid; D016572:Cyclosporine; D019802:Succinic Acid; D008274:Magnesium; D001205:Ascorbic Acid; D019297:2,4-Dinitrophenol; D010100:Oxygen