Nomura F, Noda M, Nakai T
Department of Clinical Pathology, Tsukuba University, Ibaraki, Japan.
Alcohol Clin Exp Res. 1996 Feb;20(1 Suppl):60A-62A. doi: 10.1111/j.1530-0277.1996.tb01731.x.
Mono-ADP-ribosylation, In which the ADP-ribosyl moiety is transferred from NAD to an acceptor protein, is one of the important posttranslational modifications of cellular proteins. Because mounting evidence suggests significant biological roles of this reaction in transmembrane signal transduction and other cell metabolic reactions, we assessed how long-term alcohol intake alters toxin catalyzed- and endogenous mono-ADP-ribosylation in the liver of a rat model. We first found that thiol-preactivated cholera toxin-catalyzed ADP-ribosylation of the alpha-subunit of the stimulatory GTP-binding protein was enhanced after long-term alcohol intake. Unexpectedly, but interestingly, this enhancement was not accompanied by a concomitant increase of cholera toxin-catalyzed stimulation of the adenylate cyclase activity. We also found that long-term alcohol intake remarkably enhanced endogenous mono-ADP-ribosylation of a 58 kDa protein in plasma membranes. Thus, long-term alcohol intake stimulated endogenous, as well as, toxin-catalyzed mono-ADP-ribosylations. Characterization of the 58 kDa protein may uncover pathophysiological roles of this interesting phenomenon in alcohol-induced liver damage.
单（ADP - 核糖）基化作用是细胞蛋白质重要的翻译后修饰之一，在此过程中，ADP - 核糖基部分从NAD转移至受体蛋白。由于越来越多的证据表明该反应在跨膜信号转导及其他细胞代谢反应中具有重要生物学作用，我们评估了长期摄入酒精如何改变大鼠模型肝脏中由毒素催化的和内源性的单（ADP - 核糖）基化作用。我们首先发现，长期摄入酒精后，巯基预激活的霍乱毒素催化的刺激性GTP结合蛋白α亚基的ADP - 核糖基化作用增强。出人意料但有趣的是，这种增强并未伴随着霍乱毒素催化的腺苷酸环化酶活性刺激作用的相应增加。我们还发现，长期摄入酒精显著增强了质膜中一种58 kDa蛋白的内源性单（ADP - 核糖）基化作用。因此，长期摄入酒精刺激了内源性以及毒素催化的单（ADP - 核糖）基化作用。对58 kDa蛋白的特性进行表征可能会揭示这一有趣现象在酒精性肝损伤中的病理生理作用。
