Nomura T, Higashi K, Hoshino M, Saso K, Itou M, Hoek J B
First Department Medicine, Nagoya City University, Japan.
Alcohol Clin Exp Res. 1996 Dec;20(9 Suppl):325A-329A.
The effect of oxidized and reduced glutathione on inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release from endoplasmic reticular Ca2+ stores was studied in digitonin-permeabilized hepatocytes from chronically ethanol-fed rats and pair-fed control animals. The fractional Ca2+ release induced by a subsaturating concentration of InsP3 was significantly enhanced in cells from ethanol-fed rats in the absence of a change in maximal InsP3-releasable Ca2+ pool size, and this difference was not affected by preincubation with reduced glutathione. Incubation with oxidized glutathione (1 mM) increased the efficacy of Ca2+ release by subsaturating concentrations of InsP3 in both control preparations and in cells from ethanol-fed rats. The shift in the InsP3 dose-response curve was not significantly different between the two preparations. These findings suggest that the enhanced efficacy of InsP3-induced Ca2+ release in hepatocytes from ethanol-fed rats is not caused by the oxidation of protein-bound thiol groups on the InsP3 receptor.
研究了氧化型和还原型谷胱甘肽对慢性乙醇喂养大鼠及配对喂养对照动物的洋地黄皂苷通透肝细胞中肌醇 1,4,5 -三磷酸(InsP3)诱导的内质网 Ca2+ 储存库 Ca2+ 释放的影响。在最大 InsP3 可释放 Ca2+ 池大小不变的情况下,亚饱和浓度的 InsP3 诱导的 Ca2+ 释放分数在乙醇喂养大鼠的细胞中显著增强,且这种差异不受与还原型谷胱甘肽预孵育的影响。在对照制剂和乙醇喂养大鼠的细胞中,用氧化型谷胱甘肽(1 mM)孵育均可增加亚饱和浓度的 InsP3 诱导的 Ca2+ 释放效率。两种制剂之间 InsP3 剂量反应曲线的偏移无显著差异。这些发现表明,乙醇喂养大鼠肝细胞中 InsP3 诱导的 Ca2+ 释放效率增强并非由 InsP3 受体上蛋白质结合巯基的氧化所致。