Effects of alcohol on hepatic protein metabolism and trafficking.

Research output: Contribution to journalReview article

30 Citations (Scopus)

Abstract

Ethanol administration disorders protein trafficking in the liver. The protein secretory and plasma membrane assembly pathways have been shown to be impaired in the liver of ethanol-treated animals; however, traffic along the receptor-mediated endocytosis (RME) pathway appears to be especially susceptible to alterations by ethanol. Using asialoglycoproteins as model ligands for studying RME, we have identified at least three steps of this multi-step pathway that are affected by ethanol treatment. These altered steps are recycling of the receptor, internalization of the receptor-ligand complex and dissociation of the ligand from its receptor in endosomes. Ethanol-induced derangements of RME are more severe in the perivenule region, where alcoholic liver injury starts and predominates, than in the periportal region of the liver. Recent studies have shown that the endocytosis of other ligands, including epidermal growth factor and insulin, is also altered by ethanol treatment. Mechanisms which have been proposed to explain faulty RME include: acetaldehyde adducts to tubulin resulting in impaired microtubule function, improper acidification of endosomes and defective receptor clustering in coated pits. Since RME represents an important process by which levels of various hormones, growth factors and other ligands are regulated, and since RME may also be an integral process by which the biological effects of various ligands are elicited, changes in this important process could disrupt numerous metabolic and homeostatic events in the liver.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalAlcohol and alcoholism (Oxford, Oxfordshire). Supplement.
Volume1
StatePublished - 1991

Fingerprint

Protein Transport
Endocytosis
Alcohols
Ethanol
Ligands
Liver
Endosomes
Asialoglycoproteins
Biological Phenomena
Acetaldehyde
Tubulin
Epidermal Growth Factor
Microtubules
Cluster Analysis
Intercellular Signaling Peptides and Proteins
Cell Membrane
Hormones
Insulin
Wounds and Injuries
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of alcohol on hepatic protein metabolism and trafficking. / Tuma, D. J.; Casey, C. A.; Sorrell, M. F.

In: Alcohol and alcoholism (Oxford, Oxfordshire). Supplement., Vol. 1, 1991, p. 297-303.

Research output: Contribution to journalReview article

@article{e78d5a940a534a5a81a3a4bc909494e2,
title = "Effects of alcohol on hepatic protein metabolism and trafficking.",
abstract = "Ethanol administration disorders protein trafficking in the liver. The protein secretory and plasma membrane assembly pathways have been shown to be impaired in the liver of ethanol-treated animals; however, traffic along the receptor-mediated endocytosis (RME) pathway appears to be especially susceptible to alterations by ethanol. Using asialoglycoproteins as model ligands for studying RME, we have identified at least three steps of this multi-step pathway that are affected by ethanol treatment. These altered steps are recycling of the receptor, internalization of the receptor-ligand complex and dissociation of the ligand from its receptor in endosomes. Ethanol-induced derangements of RME are more severe in the perivenule region, where alcoholic liver injury starts and predominates, than in the periportal region of the liver. Recent studies have shown that the endocytosis of other ligands, including epidermal growth factor and insulin, is also altered by ethanol treatment. Mechanisms which have been proposed to explain faulty RME include: acetaldehyde adducts to tubulin resulting in impaired microtubule function, improper acidification of endosomes and defective receptor clustering in coated pits. Since RME represents an important process by which levels of various hormones, growth factors and other ligands are regulated, and since RME may also be an integral process by which the biological effects of various ligands are elicited, changes in this important process could disrupt numerous metabolic and homeostatic events in the liver.",
author = "Tuma, {D. J.} and Casey, {C. A.} and Sorrell, {M. F.}",
year = "1991",
language = "English (US)",
volume = "1",
pages = "297--303",
journal = "Alcohol and alcoholism (Oxford, Oxfordshire). Supplement",
issn = "1358-6173",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Effects of alcohol on hepatic protein metabolism and trafficking.

AU - Tuma, D. J.

AU - Casey, C. A.

AU - Sorrell, M. F.

PY - 1991

Y1 - 1991

N2 - Ethanol administration disorders protein trafficking in the liver. The protein secretory and plasma membrane assembly pathways have been shown to be impaired in the liver of ethanol-treated animals; however, traffic along the receptor-mediated endocytosis (RME) pathway appears to be especially susceptible to alterations by ethanol. Using asialoglycoproteins as model ligands for studying RME, we have identified at least three steps of this multi-step pathway that are affected by ethanol treatment. These altered steps are recycling of the receptor, internalization of the receptor-ligand complex and dissociation of the ligand from its receptor in endosomes. Ethanol-induced derangements of RME are more severe in the perivenule region, where alcoholic liver injury starts and predominates, than in the periportal region of the liver. Recent studies have shown that the endocytosis of other ligands, including epidermal growth factor and insulin, is also altered by ethanol treatment. Mechanisms which have been proposed to explain faulty RME include: acetaldehyde adducts to tubulin resulting in impaired microtubule function, improper acidification of endosomes and defective receptor clustering in coated pits. Since RME represents an important process by which levels of various hormones, growth factors and other ligands are regulated, and since RME may also be an integral process by which the biological effects of various ligands are elicited, changes in this important process could disrupt numerous metabolic and homeostatic events in the liver.

AB - Ethanol administration disorders protein trafficking in the liver. The protein secretory and plasma membrane assembly pathways have been shown to be impaired in the liver of ethanol-treated animals; however, traffic along the receptor-mediated endocytosis (RME) pathway appears to be especially susceptible to alterations by ethanol. Using asialoglycoproteins as model ligands for studying RME, we have identified at least three steps of this multi-step pathway that are affected by ethanol treatment. These altered steps are recycling of the receptor, internalization of the receptor-ligand complex and dissociation of the ligand from its receptor in endosomes. Ethanol-induced derangements of RME are more severe in the perivenule region, where alcoholic liver injury starts and predominates, than in the periportal region of the liver. Recent studies have shown that the endocytosis of other ligands, including epidermal growth factor and insulin, is also altered by ethanol treatment. Mechanisms which have been proposed to explain faulty RME include: acetaldehyde adducts to tubulin resulting in impaired microtubule function, improper acidification of endosomes and defective receptor clustering in coated pits. Since RME represents an important process by which levels of various hormones, growth factors and other ligands are regulated, and since RME may also be an integral process by which the biological effects of various ligands are elicited, changes in this important process could disrupt numerous metabolic and homeostatic events in the liver.

UR - http://www.scopus.com/inward/record.url?scp=0026378654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026378654&partnerID=8YFLogxK

M3 - Review article

C2 - 1669008

AN - SCOPUS:0026378654

VL - 1

SP - 297

EP - 303

JO - Alcohol and alcoholism (Oxford, Oxfordshire). Supplement

JF - Alcohol and alcoholism (Oxford, Oxfordshire). Supplement

SN - 1358-6173

ER -