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Acute inhibitory effect of alpha‐mangostin on sarcoplasmic reticulum calcium‐ATPase and myocardial relaxation

机译:Alpha-mangostin对肌动蛋白钙钙 - ATP酶和心肌松弛的急性抑制作用

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Abstract The benefits of α‐mangostin for various tissues have been reported, but its effect on the heart has not been clarified. This study aimed to evaluate the effects of α‐mangostin on cardiac function. Using a cardiac sarcoplasmic reticulum (SR) membrane preparation, α‐mangostin inhibited SR Ca 2+ ‐ATPase activity in a dose‐dependent manner (IC 50 of 6.47 ± 0.7 μM). Its suppressive effect was specific to SR Ca 2+ ‐ATPase but not to myofibrillar Ca 2+ ‐ATPase. Using isolated cardiomyocytes, 50 μM of α‐mangostin significantly increased the duration of cell relengthening and increased the duration of Ca 2+ transient decay, suggesting altered myocyte relaxation. The relaxation effect of α‐mangostin was also supported in vivo after intravenous infusion. A significant suppression of both peak pressure and rate of ventricular relaxation (– dP / dt ) relative to DMSO infusion was observed. The results from the present study demonstrated that α‐mangostin exerts specific inhibitory action on SR Ca 2+ ‐ATPase activity, leading to myocardial relaxation dysfunction.
机译:摘要据报道,α-mangostin对各种组织的益处,但其对心脏的影响尚未阐明。本研究旨在评估α-血刀蛋白对心脏功能的影响。使用心肌质网(SR)膜制剂,α-芒曲蛋白以剂量依赖性方式(IC 50为6.47±0.7μm)抑制SR Ca 2+ - 酶活性。其抑制效果是特异于SR Ca 2+ -ATP酶,但不是myofibrillar ca 2+ -Atpase。使用孤立的心肌细胞,50μm的α-颅骨蛋白显着增加了细胞的持续时间,增加了Ca 2+瞬态衰退的持续时间,表明肌细胞松弛改变。静脉输注后也支持α-血刀蛋白的弛豫效果。观察到相对于DMSO输注的峰值压力和室内弛豫( - DP / DT)的显着抑制。本研究结果证明,α-芒果蛋白对SR Ca 2+ -AtPase活性产生特异性抑制作用,导致心肌松弛功能障碍。

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