Casey C A, Camacho K B, Tuma D J
Liver Study Unit, Department of Veterans Affairs Medical Center, Omaha, NE 68105.
Biochim Biophys Acta. 1992 Mar 16;1134(2):96-104. doi: 10.1016/0167-4889(92)90032-7.
The purpose of the present study was to further characterize the ethanol-induced impairments in hepatic endocytosis. Specifically, we examined the effects of ethanol treatment on receptor-ligand internalization via the coated and noncoated pit pathways. Insulin, epidermal growth factor (EGF) and asialoorosomucoid (ASOR) were used as model ligands to study internalization by isolated hepatocytes. ASOR and EGF are thought to be internalized strictly in coated pit regions of the cell membrane, while insulin may be internalized in both coated and uncoated membrane regions. Ethanol administration for 5-7 weeks decreased internalization of ASOR and EGF while internalization of insulin was unchanged during a single round of endocytosis of surface-bound ligand. Similarly, a more quantitative measure of endocytosis, the endocytic rate constant, was decreased for EGF and ASOR but not for insulin in livers of experimental rats. When endocytosis of Lucifer yellow, a fluorescent dye known to be internalized in the cell by fluid-phase endocytosis was examined, the initial rates of dye uptake were not significantly altered by alcohol administration. These results indicate that ethanol may selectively impair internalization occurring by coated pits while it has a minimal effect on initial uptake of molecules which are internalized by noncoated membrane regions.
本研究的目的是进一步描述乙醇诱导的肝脏内吞作用损伤的特征。具体而言，我们研究了乙醇处理对通过有被小窝和无被小窝途径的受体-配体内吞作用的影响。胰岛素、表皮生长因子（EGF）和去唾液酸糖蛋白（ASOR）被用作模型配体，以研究分离的肝细胞的内吞作用。ASOR和EGF被认为严格在细胞膜的有被小窝区域内吞，而胰岛素可能在有被和无被膜区域内吞。给予乙醇5至7周可降低ASOR和EGF的内吞作用，而在表面结合配体的单次内吞过程中胰岛素的内吞作用未发生变化。同样，在实验大鼠肝脏中，对EGF和ASOR而言，一种更定量的内吞作用测量方法，即内吞速率常数降低，但胰岛素的内吞速率常数未降低。当检测已知通过液相内吞作用在细胞内吞的荧光染料路西法黄的内吞作用时，乙醇给药并未显著改变染料摄取的初始速率。这些结果表明，乙醇可能选择性地损害有被小窝发生的内吞作用，而对通过无被膜区域内吞的分子的初始摄取影响最小。
