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Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore

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Author:
No author available
Journal Title:
Acta Physiologica Sinica
Issue:
5
DOI:
10.13294/j.aps.2019.0057
Key Word:
心脏;缺血再灌注;线粒体通透性转换孔;多胺;heart;ischemia/reperfusion;mitochondrial permeability transition pore;polyamines

Abstract: Polyamines (putrescine,spermidine,and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells.The study was to investigate their role in cardioprotection against ischemia/ reperfusion (I/R) injury and the underlying mechanism.Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac FR was achieved by 30 min of global ischemia followed by 120 min of reperfusion.Different concentrations of polyamines (0.1,1,10,and 15 μmol/L of putrescine,spermidine,and spermine),cyclosporin A (0.2 μmol/L),or atractyloside (20 μmol/L) were given 10 min before the onset of reperfusion.The hemodynamics were monitored;the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically;infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method;and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria.The results showed that compared to I/R alone,0.1 and 1 μmol/L polyamines treatment improved heart function,reduced LDH release,decreased infarct size,and these effects were inhibited by atractyloside (MPTP activator).In isolated mitochondria from normal rats,0.1 and 1 μmol/L polyamines treatment inhibited MPTP opening.However,10 and 15 μmol/L polyamines treatment had the opposite effects,and these effects were inhibited by cyclosporin A (MPTP inhibitor).Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.

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