dolichol-monophosphate and Alcoholism

Previous studies have demonstrated that acute ethanol intoxication affects various steps of protein glycosylation at the level of rat liver endoplasmic reticulum and Golgi apparatus. The aim of this investigation was to demonstrate whether chronic ethanol intake can induce definitive changes of liver glycoprotein processing. Rats were given ethanol by liquid diet for 8 weeks. At the end of this period the triglyceride levels in liver homogenate and microsomes were significantly higher than in controls. Isolated hepatocytes prelabelled with [3H]Na palmitate and [14C]glucosamine showed a significant storage of the lipid and carbohydrate radioactivity in microsomes and Golgi apparatus and a significant impairment of labelled glycolipoprotein secretion. Changes of the glycosylation steps were observed both in endoplasmic reticulum and in Golgi apparatus: in the former the levels of dolichyl phosphate, which is rate-limiting for the synthesis of glycoprotein, showed a significant reduction; in the latter the activity of the main enzymes responsible for the terminal glycosylation process was significantly decreased. These data suggest that an impairment of glycoprotein maturation may be involved in the pathogenesis of liver injury induced by chronic ethanol intake.

Topics: Alcoholism; Animals; Dolichol Phosphates; Dolichols; Ethanol; Fatty Liver, Alcoholic; Female; Glucosamine; Glycoproteins; Golgi Apparatus; Liver; Membrane Glycoproteins; Microsomes, Liver; Palmitic Acid; Palmitic Acids; Rats; Rats, Sprague-Dawley; Triglycerides