IRON UPTAKE FROM TRANSFERRIN AND ASIALOTRANSFERRIN BY HEPATOCYTES FROM CHRONICALLY ALCOHOL-FED RATS

Chronic alcohol intake is often associated with alterations to iron homeostasis and an increase in the serum levels of carbohydrate-deficient transferrin. As the liver is a major iron storage site and also synthesizes transferrin, the normal serum iron transport protein, the aim of this study was to test the hypothesis that these disturbances in iron homeostasis were caused by altered hepatocyte iron uptake f rom the abnormal transferrin. To achieve this, we have investigated iron uptake from both transferrin and asialotransferrin by hepatocytes from male Sprague-Dawley rats fed the De Carli and Lieber alcohol diet. Iron uptake from transferrin by hepatocytes from alcoholic rats was less than 60% that of control values, and in the presence of 50 mm ethanol decreased still further to 35% of the uptake by the corresponding control cells. Iron uptake from rat asialotransferrin was reduced in both groups when compared to that observed from normal transferrin; 13% by control cells and 39% by hepatocytes from alcohol-fed rats. Alcohol, however, had no further effect on asialotransferrin uptake by either hepatocytes from alcohol-fed rats, or their pair-fed controls. Transferrin binding to hepatocytes was also influenced by the alcohol diet. Although there was no difference in binding at 37-degrees-C, cells from alcohol-fed rats bound 85% of this total at 4-degrees-C, compared to 44% by control hepatocytes. Similar values were also obtained for hepatocyte binding of asialotransferrin; alcohol feeding resulted in an increase in binding at 4-degrees-C to 73% from 58% with control cells. The presence of alcohol in the medium did not significantly affect any of these values. These studies suggest that chronic alcohol intake decreases liver iron uptake from transferrin. The siderosis seen in some alcoholics may not be caused by iron uptake from asialotransferrin since, at least in the rat, hepatocytic iron uptake from this molecule is decreased in all groups. The data presented here suggest that there is a defect in the membrane receptor recycling mechanism for transferrin, which occurs as a result of long-term alcohol abuse.