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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. 2008; 54(6): 5-14

Purine release: a protectivesignaling mechanismof the mitochondrial permeabilitytransition pore in ischemia

Sergiy M. Nadtochiy, Dhananjaya Nauduri1,Tatyana V. Shimanskaya, Vadim F. Sagach,Paul S. Brookes.

    1Anesthesiology, University of Rochester Medical Center,Rochester NY, USA.2Circulatory Physiology Department,Bogomoletz Institute of Physiology, National Academy ofSciences, Kiev 01601, Ukraine.



Abstract

Both mitochondrial permeability transition pore (PTP) opening and purine signaling are implicated in cardioprotection via is- chemic preconditioning (IPC). The PTP opening is accomponied by release of intramitochondrial solutes, and therefore we hy- pothesized that purine release from mitochondria during PTP opening may by required for IPC signaling. Herein we show that upon PTP opening, isolated mitochondria release adenos- ine, inosine and 3’-ribosyl uric acid monophosphate (3- RUAMP), and that perfused hearts subject to IPC release Figure 6. LC-MS analysis of cardiac effluents. Hearts were subject to IR and cardiac effluents (Figure 2) analyzed by LC-MS as detailed in the methods. A: UV chromatograms of effluent from control (upper trace) and IR (lower trace) hearts. Note y-axes are not the same. B: Retention times, areas, and identities of the major numbered peaks from traces in panel A. Identities were based on retention times in UV and mass chromatograms, and m/z patterns relative to stan- dards in Figure 4. C-E: Mass spectra of peaks 1, 3 and 4 from panel A. Note the appearance in C and D of species identified as metabolites of 3-RUAMP (Figure 5D). To conserve space, spectra for all peaks are not shown. All data are representative of at least 3 independent experiments inosine and 3-RUAMP derivatives. Both these events were in- hibited by the PTP blockers cyclosporin A and sanglifehrin A. Implications for cardioprotective signaling by purines and the PTP are discussed.

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