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

我们研究了乙醇对人肝癌细胞系Hep G2去唾液酸糖蛋白受体表达的影响，该细胞已被证明维持了多种正常的肝细胞功能。乙醇处理后，细胞表面去唾液酸糖蛋白受体的数量减少到对照的60%，结合亲和力没有变化。细胞表面去唾液酸糖蛋白受体的减少与包括细胞表面和细胞内受体在内的受体总数的减少是平行的。去唾液酸糖蛋白受体的内化也减少到对照细胞的45%。用人去唾液酸糖蛋白受体寡核苷酸探针进行Northern印迹分析表明，乙醇处理的细胞中去唾液酸糖蛋白受体的特异性mRNA增加。乙醇处理的Hep G2细胞中新合成的AGPR的数量减少。当细胞从乙醇中移除时，这种增加是可逆的。这些结果表明，乙醇代谢产物直接诱导人肝细胞去唾液酸糖蛋白受体在翻译后水平下降。乙醇处理后去唾液酸糖蛋白受体mRNA的反常增加，可能是通过调控去唾液酸糖蛋白受体基因转录和/或抑制受体基因降解的反馈机制来解释。

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.