Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells

Geoffrey Milton Thiele, Jacqueline A. Miller, Lynell Warren Klassen, Dean J. Tuma

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Previous reports have shown that long-term ethanol administration aSters receptor-mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde-modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37°C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37°C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 ± 10.02 μg, 69.82 ± 5 μg, and 2.5 ± 0.42 μg of acetaldehyde-adducted albumin, respectively, during a 4-hour period. These values were decreased by 53%, 67%, and nearly 100%, respectively, in livers from ethanol-fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14C-acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde-modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde-modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long-term ethanol consumption decreases the degradation of acetaldehyde-protein adducts.

Original languageEnglish (US)
Pages (from-to)643-648
Number of pages6
JournalHepatology
Volume24
Issue number3
DOIs
StatePublished - Sep 1996

Fingerprint

Acetaldehyde
Ethanol
Endothelial Cells
Liver
Albumins
Proteins
Scavenger Receptors
Bovine Serum Albumin
Endocytosis
Formaldehyde
Proteolysis
Perfusion

ASJC Scopus subject areas

  • Hepatology

Cite this

Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells. / Thiele, Geoffrey Milton; Miller, Jacqueline A.; Klassen, Lynell Warren; Tuma, Dean J.

In: Hepatology, Vol. 24, No. 3, 09.1996, p. 643-648.

Research output: Contribution to journalArticle

@article{65f7c201c8db4c5587aa4ace72069122,
title = "Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells",
abstract = "Previous reports have shown that long-term ethanol administration aSters receptor-mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde-modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37°C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37°C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 ± 10.02 μg, 69.82 ± 5 μg, and 2.5 ± 0.42 μg of acetaldehyde-adducted albumin, respectively, during a 4-hour period. These values were decreased by 53{\%}, 67{\%}, and nearly 100{\%}, respectively, in livers from ethanol-fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14C-acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde-modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde-modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long-term ethanol consumption decreases the degradation of acetaldehyde-protein adducts.",
author = "Thiele, {Geoffrey Milton} and Miller, {Jacqueline A.} and Klassen, {Lynell Warren} and Tuma, {Dean J.}",
year = "1996",
month = "9",
doi = "10.1053/jhep.1996.v24.pm0008781337",
language = "English (US)",
volume = "24",
pages = "643--648",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells

AU - Thiele, Geoffrey Milton

AU - Miller, Jacqueline A.

AU - Klassen, Lynell Warren

AU - Tuma, Dean J.

PY - 1996/9

Y1 - 1996/9

N2 - Previous reports have shown that long-term ethanol administration aSters receptor-mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde-modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37°C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37°C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 ± 10.02 μg, 69.82 ± 5 μg, and 2.5 ± 0.42 μg of acetaldehyde-adducted albumin, respectively, during a 4-hour period. These values were decreased by 53%, 67%, and nearly 100%, respectively, in livers from ethanol-fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14C-acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde-modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde-modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long-term ethanol consumption decreases the degradation of acetaldehyde-protein adducts.

AB - Previous reports have shown that long-term ethanol administration aSters receptor-mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde-modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37°C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37°C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 ± 10.02 μg, 69.82 ± 5 μg, and 2.5 ± 0.42 μg of acetaldehyde-adducted albumin, respectively, during a 4-hour period. These values were decreased by 53%, 67%, and nearly 100%, respectively, in livers from ethanol-fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14C-acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde-modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde-modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long-term ethanol consumption decreases the degradation of acetaldehyde-protein adducts.

UR - http://www.scopus.com/inward/record.url?scp=0029793828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029793828&partnerID=8YFLogxK

U2 - 10.1053/jhep.1996.v24.pm0008781337

DO - 10.1053/jhep.1996.v24.pm0008781337

M3 - Article

C2 - 8781337

AN - SCOPUS:0029793828

VL - 24

SP - 643

EP - 648

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 3

ER -