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

Chen Hui-ying, Jia Xiao-li, Zhao Shu-qin, Zheng Wei-hong, Mei Zhi-gang, Yang Hong-wei, Zhang Shi-zhong^*

Department of Physiology, College of Medical Science, China Three Gorges University, Yichang 443002, China

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 I/R 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.

Key words: Heart; ischemia/reperfusion; mitochondrial permeability transition pore; polyamines

Received: 2019-02-25　　Accepted: 2019-07-05

Corresponding author: 张世忠　　E-mail: zhangsz@ctgu.edu.cn

DOI: 10.13294/j.aps.2019.0057

Citing This Article：

Chen Hui-ying, Jia Xiao-li, Zhao Shu-qin, Zheng Wei-hong, Mei Zhi-gang, Yang Hong-wei, Zhang Shi-zhong. Dual role of polyamines in heart ischemia/reperfusion injury through regulation of mitochondrial permeability transition pore. Acta Physiol Sin 2019; 71 (5): 681-688