Effects of long-term alcohol intake on G Protein mediated callvlar events in hepatocytes

长期饮酒对G蛋白介导的肝细胞呼叫事件的影响

• 批准号: 06670517
• 负责人: NOMURA Fumio
• 金额: $ 1.34万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670517/
• 关键词: GTP-binding protein; ADP-ribosylation; alcohol; ADPリボシル化反応; GTP結合タン白

Mono-ADP ribosylation, in which the ADP-ribosyl moiety is transferred from NAD to acceptor proteins is one of the important post-translational modifications of cellular proteins. Because mounting evidence suggests significant biological roles of this reaction in transmembrane signal transduction and other cell metabolism, we assessed how long-term alcohol intake alters toxin catalyzed-and endogenous mono-ADP ribosylation in the liver in 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. Enexpectedly, but interestingly, this enhancement was not accompanied by a comcomitant 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 58kDa protein in plasma membrnaes. Thus, long-term alcohol intake stimulated endogenous as well as toxincatalyzed mono-ADP ribosylations. Charcterization of the 58kDa protein will uncover pathophysiological roles of this interesting reaction in alcohol-induced liver damage.

单腺苷二磷酸核糖化是细胞蛋白质重要的翻译后修饰之一，它将ADP核糖基部分从NAD转移到受体蛋白上。由于越来越多的证据表明这一反应在跨膜信号转导和其他细胞代谢中具有重要的生物学作用，我们评估了长期饮酒如何改变大鼠模型中毒素催化的和内源性的单-ADP核糖化。我们首次发现，长期饮酒后，硫醇预活化的霍乱毒素催化的刺激性GTP结合蛋白α-亚基的ADP核糖化作用增强。意想不到的是，但有趣的是，这种增强并没有伴随着霍乱毒素催化的腺苷环化酶活性的增加。我们还发现，长期饮酒显著增强了质膜中一种58 kDa蛋白质的内源性单一ADP核糖化。因此，长期的酒精摄入刺激了内源性和毒素催化的单-ADP核糖化。58 kDa蛋白的特性将揭示这一有趣的反应在酒精诱导的肝损伤中的病理生理作用。

项目成果

Nomura F et al: "Effect of intrahepatic portal systemc shunting on Ammonia extraction" Hepatoliay. 20. 1478-1481 (1994)

Nomura F 等人：“肝内门系统分流对氨提取的影响”Hepatoliay。

Nomura F et al: "Alcohol Effects on toxin catalyzed-and endogenous ADP-ribosylation in rat liver plasma membranes" Alcohol and Biomedical Research. 15. 119-122 (1995)

Nomura F 等人：“酒精对大鼠肝质膜中毒素催化和内源性 ADP-核糖基化的影响”酒精和生物医学研究。

Nomura F et al: "Clinical Features of hepatocellulaa Calcinoma in the elderly" British Journal of Cancer. 70. 690-693 (1994)

Nomura F 等人：“老年人肝细胞癌的临床特征”英国癌症杂志。

野村文夫 ほか: "ラット肝細胞膜タン白のADPリボシル化反応に及ぼす長期飲酒の影響" アルコールと医学生物学. 15. 119-122 (1995)

Fumio Nomura 等人：“长期饮酒对大鼠肝细胞膜蛋白 ADP-核糖基化反应的影响”《酒精与医学生物学》15. 119-122 (1995)。

Nomura F et al: "Effects of long-term alcohol intake on ADP-ribosylation in rat liver plasma membranes" Alcoholism Clin Exp Res. (in press). (1996)

Nomura F 等人：“长期饮酒对大鼠肝脏质膜 ADP-核糖基化的影响”酒精中毒临床实验研究。