Molecular Biological Analysis of Effects of Ethanol on the Expression of Hepatic Plasma Membrane Receptor and Role in the Hepatic Disease.

乙醇对肝质膜受体表达的影响及其在肝病中的作用的分子生物学分析。

• 批准号: 01570407
• 负责人: KOHGO Yutaka
• 金额: $ 0.96万
• 依托单位: Department of Internal Medicine (Section 4), Sapporo Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570407/
• 关键词: Ethanol; Asialoglycoprotein receptor; Protein synthesis regulation; アシアロ糖蛋白白受容体; アルコ-ル; 肝細胞膜; HepG2細胞; Northern blot; Western blot

We studied the effect of ethanol on the expression of asialoglycoprotein receptor of a human hepatoma cell line, Hep G2 cells, which has been shown to maintain a large variety of normal hepatocyte functions. By ethanol treatment, the number of asialoglycoprotein receptors on the cell surface decreased to 60% of the control, with no change of binding affinity. The decrease of cell surface asialoglycoprotein receptors was parallel to that of total receptor number including surface and intracellular receptors. Internalization of asialoglycoprotein receptors was also diminlshed to 45% of control cells. Northern blot analysis by using a human asialoglycoprotein receptor oligonucleotide probe showed an increase of the specific asialoglycoprotein receptor mRNA in ethanol-treated cells. The amount of newly synthesized AGPR was decreased in ethanol-treated HeP G2 cells. This increase was reversible when cells were removed from ethanol. These results suggest that ethanol metabolite directly induce the decrease of asialoglycoprotein receptor in human hepatocytes at post translational level. The paradoxical increase of asialoglycoprotein receptor mRNA after ethanol treatment could be explained by the possible feed-back mechanism which controls asialoglycoprotein receptor gene transcription and/or impaired degradation of receptor mRNA.

我们研究了乙醇对人肝癌细胞系HEP G2细胞的肌糖蛋白受体表达的影响，该细胞已被证明可以保持大量正常的肝细胞功能。通过乙醇处理，细胞表面上的非糖蛋白受体的数量降低到对照的60％，没有结合亲和力的变化。细胞表面非糖蛋白受体的减少与包括表面和细胞内受体在内的总受体数量平行。阿乳糖蛋白受体的内在化也被减少到45％的对照细胞。通过使用人类亚糖蛋白受体寡核苷酸探针的北印迹分析显示，在乙醇处理的细胞中特异性亚氨基糖蛋白受体mRNA的增加。在乙醇处理的HEP G2细胞中，新合成的AGPR的量减少。从乙醇中去除细胞时，这种增加是可逆的。这些结果表明，乙醇代谢产物直接诱导转化后人肝细胞中亚乳糖蛋白受体的降低。乙醇处理后的亚乳糖蛋白受体mRNA的矛盾增加可以通过控制息糖蛋白受体基因转录和/或受体mRNA降解受损的可能的馈回机制来解释。

项目成果

Mogi, Y., Kohgo, Y., Nakaya, R., Kato, J., Sasaki, K., Numata, T., Nakajima, M., Kumai, R., Wu, G. H. and Niitsu, Y.: "Direct effects of ethanol on the expression of asialoglycoprotein receptor in a human hepatoma cell line." Gastroenterology.

Mogi, Y.、Kohgo, Y.、Nakaya, R.、Kato, J.、Sasaki, K.、Numata, T.、Nakajima, M.、Kumai, R.、Wu, G. H. 和 Niitsu, Y.：“

茂木 良弘 他: "ヒト肝細胞培養株を用いたアシアロ糖蛋白受容体の発現に及ぼすエタノ-ルの影響" Gastroenterology.

Yoshihiro Mogi 等人：“乙醇对使用人肝细胞培养物系的脱唾液酸糖蛋白受体表达的影响”胃肠病学。

Kohgo Y,et al: "Targeted diagnosis and therapy of liver disease: CellーSurface receptors and liver directed agents." Wu G.Y.and Wu C.H., 15 (1991)

Kohgo Y 等人：“肝脏疾病的靶向诊断和治疗：细胞表面受体和肝脏定向药物”，Wu G.Y. 和 Wu C.H.，15 (1991)。

Nakaya, R., Mogi, Y., Kato, J., Numata, T., Nakajima, M., Sasaki, K., Kohgo, Y., Niitsu, Y. and Ohta, K.: "Evaluation of serum asialoglycoprotein receptor in patients with alcoholic liver disease." Alcohol Metabolism and the Liver. 9. 118-121 (1990)

Nakaya, R.、Mogi, Y.、Kato, J.、Numata, T.、Nakajima, M.、Sasaki, K.、Kohgo, Y.、Niitsu, Y. 和 Ohta, K.：“血清脱唾液酸糖蛋白的评估

中谷 玲二,他: "各種サイトカイン(ILー1,ILー6、TNFー2)による肝アシアロ糖蛋白受容体谷の発現調節に及ぼすエタノ-ルの影響" アルコ-ル代謝と肝. 10. (1991)

Reiji Nakatani 等人：“乙醇对各种细胞因子（IL-1、IL-6、TNF-2）表达的肝脏脱唾液酸糖蛋白受体调节的影响”酒精代谢和肝脏。10。（1991）