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谷胱甘肽S-转移酶是否与肝细胞中毒伞毒素的摄取和储存有关?

Is ligandin relevant for the uptake and storage of phallotoxins in liver cells?

作者信息

Ziegler K, Grundmann E, Veil L B, Frimmer M

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1981;317(4):364-7. doi: 10.1007/BF00501320.

Abstract

To exclude an involvement of ligandin in the uptake and storage of phalloidin in hepatocytes equilibrium-dialysis studies were made with phalloidin, cholic acid and bromosulfophthalein (BSP). Binding studies with isolated ligandin indicated that the affinity of ligandin for phalloidin is low (KD = 0.8 X 10-3 M). Phalloidin neither displaced BSP (KD = 1.3 X 10-7 M) or cholic acid (KD = 7.6 X 10-5 M) from ligandin, when preloaded with these substrates. Hepatocytes prepared from rats after daily treatment with phenobarbital during 5 days contained 3-4-fold concentrations of ligandin and bound greater amounts of BSP than controls, Nevertheless the velocity of the uptake both of [3H]-demethylphalloin ([3H]-DMP) and of [35S]-BSP was not augmented. Also the sensitivity of liver cells to phalloidin was not drastically modified after induction with phenobarbital and agrees with earlier findings in vivo. We conclude that ligandin plays a negligible role in the uptake and a minor role in a storage of phallotoxins in liver cells.

摘要

为了排除配体蛋白在肝细胞中对鬼笔环肽的摄取和储存的影响,我们用鬼笔环肽、胆酸和溴磺酞钠(BSP)进行了平衡透析研究。对分离出的配体蛋白的结合研究表明,配体蛋白对鬼笔环肽的亲和力很低(KD = 0.8×10⁻³ M)。当预先加载这些底物时,鬼笔环肽既不能从配体蛋白上取代BSP(KD = 1.3×10⁻⁷ M),也不能取代胆酸(KD = 7.6×10⁻⁵ M)。在连续5天每天用苯巴比妥处理的大鼠制备的肝细胞中,配体蛋白的浓度是对照组的3 - 4倍,并且比对照组结合了更多的BSP。然而,[³H] - 去甲基鬼笔环肽([³H] - DMP)和[³⁵S] - BSP的摄取速度并没有增加。在用苯巴比妥诱导后,肝细胞对鬼笔环肽的敏感性也没有显著改变,这与早期的体内研究结果一致。我们得出结论,配体蛋白在肝细胞摄取鬼笔毒素的过程中作用可忽略不计,在储存鬼笔毒素方面起次要作用。

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