Chronic ethanol administration impairs receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes

✍ Scribed by Douglas D. Dalke; Michael F. Sorrell; Carol A. Casey; Dean J. Tuma

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 801 KB
• Volume: 12
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840120502

✦ Synopsis

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 d a c e receptors rather than by changes in receptor affinity. When hepatocytes were incubated at 37" C in the presence of a large saturating concentration of epidermal growth factor (80 nmolb), 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 d a c e -b o u n d ligand was internalized and subsequently degraded in cells from the ethanoltreated 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 maljor impairment appears to be a reduction of cell d a c e 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. (HEPATOLOGY 1990;12:1085-1091.)

Ethanol administration disorders protein trafficking in the liver (1). Acute and chronic ethanol administration have been shown to alter plasma protein se-