Nomura F, Miyake M, Noda M, Itoga S, Nakai T
Department of Clinical Pathology, Institute of Clinical Medicine, Tsukuba University, Ibaraki, Japan.
Alcohol Clin Exp Res. 1998 May;22(S3 Pt 1):121S-124S. doi: 10.1111/acer.1998.22.s3_part1.121s.
ADP-ribosylation is a posttranslational protein modification catalyzed by two classes of enzymes: mono-ADP-ribosyltransferase and poly-ADP-ribose polymerases. We previously demonstrated that long-term alcohol intake remarkably enhanced an endogenous ADP-ribosylation of a 58 kDa protein in rat liver and also identified the 58 kDa protein as phosphoglucomutase (PGM). To assess biological significance of this phenomenon, we tested the effects of long-term alcohol intake on PGM activities in connection with posttranslational modification of the protein. ADP-ribosylation of PGM was mono- rather than poly-ADP-ribosylation. Also, nonenzymatic binding of ADP-ribose was excluded. It was of note that ADP-ribosylation of exogenous PGM was remarkably increased by adding rat liver plasma membranes, and that the extent of the increase was greater in alcohol-fed rats than in pair-fed controls. Furthermore, PGM activities were significantly increased after long-term alcohol intake concomitant with increased ADP-ribosyltransferase activities toward PGM. In view of the variety of roles of PGM in the liver, such as carbohydrate metabolism and Ca2+ homeostasis, it is tempting to speculate that increased ADP-ribosylation of PGM may play a role in long-term alcohol effects on hepatocytes.
ADP核糖基化是一种由两类酶催化的翻译后蛋白质修饰：单ADP核糖基转移酶和聚ADP核糖聚合酶。我们之前证明，长期摄入酒精可显著增强大鼠肝脏中一种58 kDa蛋白质的内源性ADP核糖基化，并且还鉴定出该58 kDa蛋白质为磷酸葡萄糖变位酶（PGM）。为了评估这一现象的生物学意义，我们结合该蛋白质的翻译后修饰测试了长期摄入酒精对PGM活性的影响。PGM的ADP核糖基化是单ADP核糖基化而非聚ADP核糖基化。此外，排除了ADP核糖的非酶结合。值得注意的是，添加大鼠肝脏质膜后，外源性PGM的ADP核糖基化显著增加，并且在酒精喂养的大鼠中增加的程度大于配对喂养的对照组。此外，长期摄入酒精后，PGM活性显著增加，同时对PGM的ADP核糖基转移酶活性也增加。鉴于PGM在肝脏中的多种作用，如碳水化合物代谢和Ca2+稳态，很容易推测PGM的ADP核糖基化增加可能在长期酒精对肝细胞的影响中起作用。
