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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2011; 57(4): 34-45


Mitochondriapermeability transition as a target for ischemic preconditioning

Y.V. Goshovska, T.V. Shimanskaya, O.M. Rudyk, Y.P. Korkach, V.F. Sagach.

    О.О. Bogomolets Institute of Physiology, National Akademyof Sciences of Ukraine, Kyiv


Abstract

The ischemic preconditioning (IPC) limits myocardial injury provoked by a subsequent prolonged ischemia-reperfusion (I/R). The underlying mechanisms of enhanced resistance of heart are actively studied, but for sure it was established that mito­chondria play a major role in IPC-stimulated adaptation to ischemia. In this article we present and discuss evidences that cardioprotective effect of IPC is mediated by inhibition of mitochondria permeability transition pore (MPTP) opening. It was shown that IPC effectively prevents the excessive pro­duction of ROS by mitochondria during I/R and promotes a more complete restoration of function of isolated rat hearts. It was revealed that MPTP formation due to I/R was inhibited in IPC heart. Mitochondrial factor, the marker of MPTP open­ing found in outflow probes, was released in much lesser amounts in IPC hearts that in non-IPC. Furthermore, mito­chondria isolated from IPC hearts showed a decreased sensi­tivity to calcium ions, a MPTP inductor, and, thus, massive MPTP-depended swelling of mitochondria was abrogated in IPC hearts. In our experiments we observed slight increase in inducible NOS activity right after short ischemic stimuli. We suppose that increased NO production by iNOS is involved in inhibition of MPTP and this may be one of the possible mecha­nisms of decreased sensitivity of mitochondria to calcium ions. It is concluded that among the processes involved in formation of cardioprotective effect of IPC, a reduction of membrane permeability due to the inhibition of MPTP opening plays a crucial role.

Keywords: isolated heart, ischemic precondition, nitric oxide,iNOS, MPTP

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