Ethanol-dependent induction of bilirubin UDP-glucuronosyl-transferase in rat liver is mediated by Kupffer cells.
Recently we have reported that bilirubin UDP-glucuronosyltransferase (UGT1A1) is induced in rat liver by chronic ethanol treatment. Several studies have shown that Kupffer cells play a central role in the mediation of various hepatic effects of chronic alcohol consumption. In the present work, the participation of Kupffer cells in the ethanol dependent induction of UGT1A1 was investigated. A group of rats was pretreated with gadolinium chloride, a known Kupffer-cell-depleting agent. We compared the effect of chronic ethanol ingestion on UGT1A1 expression in the liver of normal and gadolinium chloride treated rats. The effect of ethanol on bilirubin glucuronidation was completely prevented in Kupffer cell deficient rats. The western and northern blot analyses showed that the increase of both the protein and mRNA of UGT1A1 was prevented in these animals. These results suggest that Kupffer cells play a major role in the mediation of ethanol-stimulated induction of UGT1A1 in liver parenchymal cells.
Kardon
Tamás
T
Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
Mile
Valéria
V
Bánhegyi
Gábor
G
Csala
Miklós
M
Burchell
Brian
B
Mandl
József
J
Braun
László
L
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D007728:Kupffer Cells / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D000431:Ethanol; D005682:Gadolinium; D014453:Glucuronosyltransferase; D012333:RNA, Messenger; D000099148:UGT1A1 Enzyme; C499946:Ugt1a1 protein, rat; C038958:gadolinium chloride