Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver

Carol A Casey, Gary D Volentine, Christopher J. Jankovich, Sandra L. Kragskow, Dean J. Tuma

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1117-1123
Number of pages7
JournalBiochemical Pharmacology
Volume40
Issue number5
DOIs
StatePublished - Sep 1 1990

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Asialoglycoproteins
Liver
Rats
Ethanol
Endocytosis
Degradation
Ligands
Animals
Lysosomes
Hepatocytes
Perfusion
Subcellular Fractions
Endosomes
Cell membranes
Nutrition
Sprague Dawley Rats
Glycoproteins
Carbohydrates
Cell Membrane
asialoorosomucoid

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Effect of chronic ethanol administration on the uptake and degradation of asialoglycoproteins by the perfused rat liver. / Casey, Carol A; Volentine, Gary D; Jankovich, Christopher J.; Kragskow, Sandra L.; Tuma, Dean J.

In: Biochemical Pharmacology, Vol. 40, No. 5, 01.09.1990, p. 1117-1123.

Research output: Contribution to journalArticle

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