Dalke D D, Sorrell M F, Casey C A, Tuma D J
Department of Veterans Affairs Medical Center, Omaha, Nebraska 68105.
Hepatology. 1990 Nov;12(5):1085-91. doi: 10.1002/hep.1840120502.
The effects of chronic ethanol administration on the receptor-mediated endocytosis of epidermal growth factor were studied in isolated rat hepatocytes. In initial experiments, it was demonstrated that significantly less ligand was bound by hepatocytes isolated from rats fed an ethanol liquid diet for 5 to 7 wk than by cells isolated from chow-fed or pair-fed controls. Reduced binding was shown to be primarily caused by a decreased number of surface receptors rather than by changes in receptor affinity. When hepatocytes were incubated at 37 degrees C in the presence of a large saturating concentration of epidermal growth factor (80 nmol/L), intracellular levels of the ligand were significantly lower in cells from the ethanol-fed animals. However, no effect on degradation of the ligand was observed under those conditions. A defect in the initial stages of receptor-ligand internalization was also indicated because less surface-bound ligand was internalized and subsequently degraded in cells from the ethanol-treated rats. When the endocytosis of a lower, more physiological concentration of the growth factor (0.5 nmol/L) was studied, both the uptake of ligand and its degradation were markedly impaired in hepatocytes from the ethanol-fed animals. These results indicate that chronic ethanol administration impairs the receptor-mediated endocytosis of epidermal growth factor by the liver. The major impairment appears to be a reduction of cell surface receptors; however, other steps of the endocytotic pathway also appear to be affected. These altered steps include defective receptor-ligand internalization and changes in intracellular processing of the ligand leading to decreased degradation.
在分离的大鼠肝细胞中研究了长期给予乙醇对表皮生长因子受体介导的内吞作用的影响。在最初的实验中，结果表明，从喂食乙醇液体饲料5至7周的大鼠分离的肝细胞结合的配体明显少于从喂食普通饲料或配对喂养对照组分离的细胞。结合减少主要是由于表面受体数量减少，而非受体亲和力的变化。当肝细胞在37℃下于高饱和浓度的表皮生长因子（80 nmol/L）存在下孵育时，来自喂食乙醇动物的细胞中配体的细胞内水平显著降低。然而，在这些条件下未观察到对配体降解的影响。受体 - 配体内化初始阶段的缺陷也有体现，因为在来自乙醇处理大鼠的细胞中，较少的表面结合配体被内化并随后降解。当研究较低的、更接近生理浓度的生长因子（0.5 nmol/L）的内吞作用时，来自喂食乙醇动物的肝细胞中配体的摄取及其降解均明显受损。这些结果表明，长期给予乙醇会损害肝脏中表皮生长因子受体介导的内吞作用。主要损害似乎是细胞表面受体减少；然而，内吞途径的其他步骤似乎也受到影响。这些改变的步骤包括受体 - 配体内化缺陷以及配体细胞内加工变化导致降解减少。
