The effect of ethanol on the uptake, binding, and desialylation of transferrin by rat liver endothelium: implications in the pathogenesis of alcohol-associated hepatic siderosis.
Chronic alcoholism has been reported to be associated with a reduced carbohydrate content of transferrin (TF), particularly, its reduced sialylation state. Low sialylation state of TF now serves as an objective marker of chronic alcohol abuse. To investigate the pathophysiological significance of this finding in relation to hepatic siderosis, also commonly associated with chronic alcoholism, the authors have investigated the effect of ethanol on the uptake, binding, and desialylation of transferrin by isolated rat liver endothelium in vitro. In pulse-chase experiments, transferrin labeled with either 125I (protein-labeled) or 3H (sialic acid-labeled) was incubated with isolated, fractionated liver endothelium with and without ethanol, and the supernates were subjected to column chromatography using RCA120- agarose. Incubation of the endothelium with increasing concentrations of ethanol resulted in a progressive increase in the desialylation rate of transferrin which was maximal when 160 mM concentration of ethanol was used. These data indicate that ethanol significantly promotes the desialylation of transferrin by rat liver endothelium. The implications of these findings in the pathogenesis of hepatic siderosis of the alcoholic are discussed.
Mihas
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AA
Department of Medicine, VAMC, Jackson, MS 39216.
Tavassoli
M
M
D000079:Acetaldehyde / Q000378:metabolism; D000085:Acetates / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004727:Endothelium / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D012806:Siderosis / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*
D000085:Acetates; D012794:Sialic Acids; D014168:Transferrin; D000431:Ethanol; D007501:Iron; D000079:Acetaldehyde