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Signal transduction in hepatocytes-Long-term alcohol effects on small G-proteins

肝细胞信号转导——长期酒精对小G蛋白的影响

基本信息

批准号：
08670552
负责人：
NOMURA Fumio
金额：
$ 1.41万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

ADP-ribosylation is a post-translational protein modification which in turn alters several regulatory proteins in mammalian cells. We demonstrated that long-term alcohol intake enhanced the ADP-ribosylation of a 58kDa protein in rat liver plasma membranes. To assess the biological significance of this phenomenon, we partially purified the 58kDa acceptor protein from solubilized rat liver homogenates by two sequential preparative HPLCs. Microsequencing revealed that it was phosphoglucomutase (EC 5,4,2,2). This enzyme underwent negligible auto ADP-ribosylation, but the ADP-ribosylation was remarkably increased by adding rat liver plasma membrances. The extent of the increase was greater in alcohol-fed rats than in pair-fed controls, suggesting enhanced enzyme activities toward ADP-ribosylation of phosphoglucomutase after chronic alcohol consumption. Several important enzymes are ADP-ribosylated, after which their activities are modified. The results of this study showed that phosphoglucomutase is a novel substrate for ADP-ribosylation in the liver and that the ADP-ribosylation is increased after chronic alcohol consumption. In view of the variety of roles of phosphoglucomutase in the liver (carbohydrate metabolism and Ca^<2+>homeostasis), specific roles of this modification in terms of alcohol effects on hepatocytes may deserve further investigation.

adp核糖基化是一种翻译后的蛋白质修饰，它反过来改变了哺乳动物细胞中的几种调节蛋白。我们证明，长期饮酒增强了大鼠肝质膜中58kDa蛋白的adp核糖基化。为了评估这种现象的生物学意义，我们从溶解的大鼠肝脏匀浆中通过两个顺序制备的高效液相色谱部分纯化了58kDa受体蛋白。微测序结果显示其为磷酸葡萄糖糖化酶（ec5,4,2,2）。该酶可忽略adp核糖基化，但加入大鼠肝细胞膜后，adp核糖基化显著增加。酒精喂养的大鼠比配对喂养的对照组增加的程度更大，这表明慢性酒精摄入后磷酸葡萄糖糖化酶的adp核糖基化酶活性增强。一些重要的酶被adp核糖化，之后它们的活性被修饰。本研究结果表明，磷酸葡萄糖糖糖化酶是肝脏中adp -核糖基化的新底物，并且慢性饮酒后adp -核糖基化增加。鉴于磷酸葡萄糖糖糖化酶在肝脏中的多种作用（碳水化合物代谢和Ca^<2+ bb0稳态），这种修饰在酒精对肝细胞的作用方面的具体作用可能值得进一步研究。