Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells.
Previous reports have shown that long-term ethanol administration alters 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 degrees C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37 degrees C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 +/- 10.02 microg, 69.82 +/- 5 microg, and 2.5 +/- 0.42 microg 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.
Thiele
G M
GM
University of Nebraska Medical Center, Omaha, USA.
Miller
J A
JA
Klassen
L W
LW
Tuma
D J
DJ
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008102:Liver Circulation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors
D012710:Serum Albumin, Bovine; D000431:Ethanol; D000079:Acetaldehyde