EFFECT OF CHRONIC ETHANOL ADMINISTRATION ON TOTAL ASIALOGLYCOPROTEIN RECEPTOR CONTENT AND INTRACELLULAR PROCESSING OF ASIALOOROSOMUCOID IN ISOLATED RAT HEPATOCYTES

被引:34
作者
CASEY, CA
KRAGSKOW, SL
SORRELL, MF
TUMA, DJ
机构
[1] UNIV NEBRASKA,MED CTR,DEPT MED,OMAHA,NE 68105
[2] UNIV NEBRASKA,MED CTR,DEPT BIOCHEM,OMAHA,NE 68105
关键词
(Rat hepatocyte); Asialoglycoprotein receptor; Asialoorosomucoid; Ethanol; Receptor mediated endocytosis;
D O I
10.1016/0167-4889(90)90049-J
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic ethanol administration markedly impairs the process of receptor-mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver (Casey et al. (1987) J. Biol. Chem. 262, 2704-2710). Decreased surface binding was the major defect reported in our initial study, along with impaired internalization and degradation of 125I-ASOR in chronically-fed ethanol animals. In this study, we further characterized these impairments by examining the content of intracellular receptors and by investigating ligand processing directed by these intracellular receptors. Ethanol administration for 5-7 weeks decreased intracellular ASOR receptor content by 40%, a result which was confirmed by using both a ligand-binding assay and an antibody-binding assay. In addition to a decreased number of intracellular receptors, an impairment in intracellular processing of receptor-ligand complexes was identified. In ethanol-fed animals, dissociation of receptor-ligand complexes was decreased during steady-state conditions of endocytosis at 37°C. Impaired receptor-ligand dissociation did not alter the fate of the ligand which was to undergo diacytosis (ligand recycling), but did appear to impair degradation of intracellular ligand. These results indicate that chronic ethanol administration decreases ligand binding due to a decreased number of receptors and impairs intracellular processing of ASOR in hepatocytes. © 1990.
引用
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页码:1 / 8
页数:8
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