TY - JOUR
T1 - Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver
AU - Casey, Carol A.
AU - Volentine, Gary D.
AU - Jankovich, Christopher J.
AU - Kragskow, Sandra L.
AU - Tuma, Dean J.
N1 - Funding Information:
Acknowledgements-This research was supported by Grants AA07846 and AA04961 from the National Institutes on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs. We gratefully acknowledge the technical assistance of Benita Tworek and Mary Barak-Bernhagen for some of the studies and thank Alieen Simons skillful preparation of the manuscript.
PY - 1990/9/1
Y1 - 1990/9/1
N2 - We have shown previously reduced binding, internalization, degradation and receptorligand dissociation during receptor-mediated endocytosis (RME) of 125I-asialoorosomucoid (ASOR) by hepatocytes isolated from rats fed ethanol for 4-6 weeks. In the present study, we investigated the effect of ethanol feeding on RME by using the intact perfused liver as a model. Male, Sprague-Dawley rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric carbohydrate. Receptor-mediated endocytosis of 125I-ASOR was then examined over a time course of perfusion. In all cases, clearance of the labeled glycoprotein was followed by a slower but steady appearance of acid-soluble products in the medium. Ethanol-fed animals had a significantly (P < 0.01) slower rate of clearance of the labeled ligand from the circulating perfusate than did control animals. Impairment of ASOR surface binding and degradation in ethanol-fed animals was also demonstrated in this model. When we examined the subcellular distribution of labeled ligand after various times of perfusion, we found that in control livers, a shift of radiolabeled ligand from the subcellular fractions containing endosomes and plasma membranes to fractions containing lysosomes occurred, while significantly less ligand was shifted to the lysosomes of ethanol-treated rats. These results show that ethanol administration inhibits RME of ASOR in the isolated perfused liver model, thus confirming our earlier reported defects in isolated hepatocytes. In addition, transport of ligand along the intracellular RME pathway was also shown to be altered by ethanol treatment as indicated by the impaired movement of ASOR from the endosomal to the lysosomal compartment.
AB - We have shown previously reduced binding, internalization, degradation and receptorligand dissociation during receptor-mediated endocytosis (RME) of 125I-asialoorosomucoid (ASOR) by hepatocytes isolated from rats fed ethanol for 4-6 weeks. In the present study, we investigated the effect of ethanol feeding on RME by using the intact perfused liver as a model. Male, Sprague-Dawley rats were fed a liquid diet containing either ethanol (36% of calories) or isocaloric carbohydrate. Receptor-mediated endocytosis of 125I-ASOR was then examined over a time course of perfusion. In all cases, clearance of the labeled glycoprotein was followed by a slower but steady appearance of acid-soluble products in the medium. Ethanol-fed animals had a significantly (P < 0.01) slower rate of clearance of the labeled ligand from the circulating perfusate than did control animals. Impairment of ASOR surface binding and degradation in ethanol-fed animals was also demonstrated in this model. When we examined the subcellular distribution of labeled ligand after various times of perfusion, we found that in control livers, a shift of radiolabeled ligand from the subcellular fractions containing endosomes and plasma membranes to fractions containing lysosomes occurred, while significantly less ligand was shifted to the lysosomes of ethanol-treated rats. These results show that ethanol administration inhibits RME of ASOR in the isolated perfused liver model, thus confirming our earlier reported defects in isolated hepatocytes. In addition, transport of ligand along the intracellular RME pathway was also shown to be altered by ethanol treatment as indicated by the impaired movement of ASOR from the endosomal to the lysosomal compartment.
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U2 - 10.1016/0006-2952(90)90501-B
DO - 10.1016/0006-2952(90)90501-B
M3 - Article
C2 - 2390108
AN - SCOPUS:0025044828
SN - 0006-2952
VL - 40
SP - 1117
EP - 1123
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 5
ER -