Kohgo Y, Mogi Y, Kato J, Nakaya R, Nakajima M, Katsuki S, Niitsu Y
Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
J Gastroenterol. 1994 Oct;29(5):598-604. doi: 10.1007/BF02365442.
The effect of ethanol on the expression of asialoglycoprotein receptor protein and its mRNA was studied in a human hepatoma cell line, HepG2. The number of asialoglycoprotein receptors on the cell surface was decreased to 60% of the control level, without a loss in affinity, by incubating the cells with 100 mM ethanol. The decrease in cell surface asialoglycoprotein receptors was paralleled by a decrease in total receptor numbers, including intracellular and surface receptors. The internalization of asialoglycoprotein was also diminished, to 44% of that in control cells. The decreases in cell surface receptors and total receptor numbers were partially restored by 2 mM 4-methylpyrazole, suggesting that ethanol metabolites participated in the diminution of asialoglycoprotein receptor expression. However, the steady-state expression of asialoglycoprotein receptor mRNA was increased in ethanol-treated cells and further augmented by a longer ethanol exposure. These paradoxical results, i.e., the decrease of asialoglycoprotein receptor protein and the increase of its mRNA expression, suggest that the reduction in the asialoglycoprotein receptor protein is a post-transcriptional event and that a possible feedback regulatory mechanism may control asialoglycoprotein receptor gene transcription and/or impair the degradation of its mRNA.
在人肝癌细胞系HepG2中研究了乙醇对去唾液酸糖蛋白受体蛋白及其mRNA表达的影响。通过用100 mM乙醇孵育细胞，细胞表面去唾液酸糖蛋白受体的数量降至对照水平的60%，而亲和力没有损失。细胞表面去唾液酸糖蛋白受体的减少与总受体数量的减少平行，总受体数量包括细胞内和表面受体。去唾液酸糖蛋白的内化也减少至对照细胞的44%。2 mM 4-甲基吡唑部分恢复了细胞表面受体和总受体数量的减少，表明乙醇代谢产物参与了去唾液酸糖蛋白受体表达的减少。然而，在乙醇处理的细胞中，去唾液酸糖蛋白受体mRNA的稳态表达增加，并且随着乙醇暴露时间延长而进一步增强。这些矛盾的结果，即去唾液酸糖蛋白受体蛋白减少而其mRNA表达增加，表明去唾液酸糖蛋白受体蛋白的减少是转录后事件，并且可能存在反馈调节机制控制去唾液酸糖蛋白受体基因转录和/或损害其mRNA的降解。
