Purine release: a protective signaling mechanism of the mitochondrial permeability transition pore in ischemia.
Both mitochondrial permeability transition pore (PTP) opening and purine signaling are implicated in cardioprotection via ischemic preconditioning (IPC). The PTP opening is accomponied by release ofintramitochondrial solutes, and therefore we hypothesized that purine release from mitochondria during PTP opening may by required for IPC signaling. Herein we show that upon PTP opening, isolated mitochondria release adenosine, inosine and 3'-ribosyl uric acid monophosphate (3-RUAMP), and that perfused hearts subject to IPC release inosine and 3-RUAMP derivatives. Both these events were inhibited by the PTP blockers cyclosporin A and sanglifehrin A. Implications for cardioprotective signaling by purines and the PTP are discussed.
Nadtochiy
Sergiy M
SM
Department of Anesthesiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Nauduri
Dhananjaya
D
Shimanskaya
Tatyana V
TV
Sagach
Vadim F
VF
Brookes
Paul S
PS
D000818:Animals; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D008297:Male; D013058:Mass Spectrometry; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011687:Purines