Effect of inductors and inhibitors of the mitochondrial permeability transition pore (mpt) on its opening and release of unidentifiedmitochondrial factor
V.F. Sagach, G.L.. Vavilova, N.A. Strutinskaya, O.V. Akopova
Ін-т фізіології ім. О.О.Богомольця НАН України,КиївІн-т фізіології ім. О.О.Богомольця НАН України,КиївІн-т фізіології ім. О.О.Богомольця НАН України,Київ
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Abstract
The release of an unidentified substance (factor) induced by
sulfhydryl group (SH) modifier and mitochondrial permeability
transition pore (MPT) inductor phenylarsine oxide
(PAO) has been found in vitro on isolated guinea-pig and rat
heart mitochondria. The factor was also released at oxidative
stress. The factor release induced by PAO was inhibited by
cyclosporin A (CsA), the MPT inhibitor. Protective actions
of antioxidants melatonin and trolox in vitro and in vivo, as
well as dithiothreitol (DTT) and diethylmaleat (DEM) were
studied. The influences of nitric oxide (NO) donor, sodium
nitroprusside (SNP) on the mitochondrial factor release were
also studied. We have shown the participation of this agent in
the regulation of factor formation after inhibition of NO-synthase
activity (NOS) by aminoguanidine. The data were obtained
about MPT-opening after Ca2+ loading and under the
influence of the MPT inductor PAO, inhibited by CsA. The
results obtained on isolated mitochondria are in a good agreement
with the those on the isolated guinea-pig heart after
myocardial ischemia-reperfusion. It was concluded that mitochondria
are essential for the factor formation and its release under
ischemia-reperfusion of the myocardium.
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