Release of unidentified substances of mitochondrial origin--evidence of mitochondrial permeability transition pore opening in the heart mitochondria of rats
Sahach, V.F.; Vavilova, H.L.; Rudyk, O.V.; Strutyns'ka, N.A.
Fiziolohichnyi Zhurnal 49(5): 3-12
2003
ISSN/ISBN: 2522-9028 PMID: 14663885 Document Number: 555253
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.