Nomura F, Noda M, Miyake M, Nakai T
Department of Clinical Pathology, Institute of Clinical Medicine, Tsukuba University, Ibaraki, Japan.
Hepatology. 1996 Nov;24(5):1246-9. doi: 10.1053/jhep.1996.v24.pm0008903405.
Adenosine diphosphate (ADP)-ribosylation is a posttranslational protein modification that, in turn, alters several regulatory proteins in mammalian cells. We demonstrated that long-term alcohol intake enhanced the ADP-ribosylation of a 58-kd protein in rat liver plasma membranes. To assess the biological significance of this phenomenon, we partially purified the 58-kd acceptor protein from solubilized rat liver homogenates by two sequential preparative high-pressure liquid chromatographies. Microsequencing revealed that it was phosphoglucomutase (PGM) (EC 5,4,2,2). This enzyme underwent negligible auto ADP-ribosylation, but the ADP-ribosylation was remarkably increased by adding rat liver plasma membranes. The extent of the increase was greater in alcohol-fed rats than in pair-fed controls, suggesting enhanced enzyme activities toward ADP-ribosylation of PGM after chronic alcohol consumption. Several important enzymes are ADP-ribosylated, after which their activities are modified. The results of this study showed that PGM 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 PGM in the liver (carbohydrate metabolism and Ca2+ homeostasis), specific roles of this modification in terms of the effects of alcohol on hepatocytes may deserve further investigation.
二磷酸腺苷（ADP）-核糖基化是一种翻译后蛋白质修饰，反过来会改变哺乳动物细胞中的几种调节蛋白。我们证明，长期摄入酒精会增强大鼠肝细胞膜中一种58 kDa蛋白的ADP-核糖基化。为了评估这一现象的生物学意义，我们通过两次连续的制备型高压液相色谱法从溶解的大鼠肝匀浆中部分纯化了58 kDa的受体蛋白。微量测序显示它是磷酸葡萄糖变位酶（PGM）（EC 5,4,2,2）。这种酶的自身ADP-核糖基化可以忽略不计，但加入大鼠肝细胞膜后，ADP-核糖基化显著增加。酒精喂养的大鼠中增加的程度比配对喂养的对照组更大，这表明长期摄入酒精后，PGM的ADP-核糖基化酶活性增强。几种重要的酶会发生ADP-核糖基化，之后其活性会被改变。本研究结果表明，PGM是肝脏中ADP-核糖基化的一种新底物，并且长期摄入酒精后ADP-核糖基化会增加。鉴于PGM在肝脏中的多种作用（碳水化合物代谢和Ca2+稳态），这种修饰在酒精对肝细胞影响方面的具体作用可能值得进一步研究。
