Ethanol-impaired hepatic protein trafficking: concepts from the asialoglycoprotein receptor system.
OBJECTIVE
Alcohol abuse with its resulting liver injury is a major health problem worldwide. Recent studies have shown that the process of receptor-mediated endocytosis (RME) is especially susceptible to the deleterious effects of ethanol.


METHODS
In our laboratory, we have shown that after as early as 1 week of ethanol administration, binding, internalization and degradation of asialoorosomucoid, a ligand for the asialoglycoprotein receptor (ASGP-R), is significantly impaired. We have also demonstrated that ethanol administration impairs ATP-dependent acidification of prelysosomal endosomes.


RESULTS
These impairments are seen using ligands internalized by the non-specific process of fluid phase endocytosis as well as those internalized by coated pit endocytosis. In addition, we have identified ethanol-induced alterations in post-translational modifications of the receptor including phosphorylation and fatty acid modification (palmitoylation).


CONCLUSIONS
Impaired function of this receptor could lead to alterations of membrane internalization events after ethanol administration and contribute to ethanol-induced alterations in protein trafficking and signaling in the liver.
McVicker
B L
BL
Department of Internal Medicine, University of Nebraska Medical Center and the Division of Veterans Affairs, Omaha 68105, USA.
Casey
C A
CA
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002966:Clathrin; D011506:Proteins; D011956:Receptors, Cell Surface; D000431:Ethanol