[Release of unidentified substances of mitochondrial origin--evidence of mitochondrial permeability transition pore opening in the heart mitochondria of rats ].
In experiments in vitro on isolated heart mitochondria of rats, an activation of mitochondrial permeability transition pore (PTP) was induced by either modelling an oxidative stress with PTP-inductor phenylarsine oxide (PAO) or by calcium overload (CaCl2). PTP-opening was determined spectrophotometrically (lambda = 520 nm) by a decrease in an optical density (OD), resulting from mitochondrial swelling. We also observed a release of mitochondrial unidentified substances (mitochondrial factor, MF) registered spectrophotometrically in a range of waves lambda = 230-260 nm. Both correlation between mitochondrial swelling and a release of the mitochondrial factor have been found in experiments with PAO at concentrations 10(-7)-10(-4) mol/l, and in those with CaCl2 at concentrations 10(-6)-10(-4) mol/l. The classical inhibitor of mitochondrial PTP cyclosporin A (Cs A, 10(-5) mol/l) inhibited mitochondrial swelling and a release of that factor completely. Our experimental data give evidence for mitochondrial origin of the factor and its release following PTP-opening by PTP-inductors--PAO and CaCl2. Mitochondrial swelling that accompanied the factor's release might contribute to PTP-opening and be useful in defining the mitochondrial sensitivity either with inductors or inhibitors of mitochondrial PTP in different tissues under normal and pathological states of organism.
Sahach
V F
VF
O.O. Bohomoletz Institute of Physiology, National Academy of Science of Ukraine, Kiev.
Vavilova
H L
HL
Rudyk
O V
OV
Strutyns'ka
N A
NA
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D001152:Arsenicals; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; C029341:oxophenylarsine; D016572:Cyclosporine; D002122:Calcium Chloride