Ethanol-impaired hepatic protein trafficking: Concepts from the asialoglycoprotein receptor system

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Abstract

Objectives: 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. Design and 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.

Original languageEnglish (US)
Pages (from-to)557-561
Number of pages5
JournalClinical Biochemistry
Volume32
Issue number7
DOIs
StatePublished - Oct 1 1999

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Asialoglycoprotein Receptor
Protein Transport
Ethanol
Liver
Endocytosis
Proteins
Lipoylation
Ligands
Phosphorylation
Acidification
Endosomes
Post Translational Protein Processing
Medical problems
Alcoholism
Fatty Acids
Adenosine Triphosphate
Alcohols
Membranes
Degradation
Fluids

Keywords

  • Alcohol
  • Endocytosis
  • Hepatocytes
  • Liver
  • Protein trafficking
  • Receptor-mediated endocytosis
  • Receptors

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

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title = "Ethanol-impaired hepatic protein trafficking: Concepts from the asialoglycoprotein receptor system",
abstract = "Objectives: 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. Design and 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.",
keywords = "Alcohol, Endocytosis, Hepatocytes, Liver, Protein trafficking, Receptor-mediated endocytosis, Receptors",
author = "McVicker, {Benita L} and Casey, {Carol A}",
year = "1999",
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T1 - Ethanol-impaired hepatic protein trafficking

T2 - Concepts from the asialoglycoprotein receptor system

AU - McVicker, Benita L

AU - Casey, Carol A

PY - 1999/10/1

Y1 - 1999/10/1

N2 - Objectives: 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. Design and 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.

AB - Objectives: 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. Design and 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.

KW - Alcohol

KW - Endocytosis

KW - Hepatocytes

KW - Liver

KW - Protein trafficking

KW - Receptor-mediated endocytosis

KW - Receptors

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