Transcriptional induction of bilirubin UDP-glucuronosyltransrase by ethanol in rat liver.
Several drug-metabolizing enzymes including bilirubin UDP-glucuronosyltransferase (UGT1A1) are influenced by long-term ethanol consumption. In the present study, the activity and expression of UGT1A1 were investigated in livers of ethanol-treated rats. Animals were treated daily for 15 days with ethanol or isocaloric amount of glucose solution by gastric intubation. Microsomes and total RNA were prepared from the liver of rats and analyzed by Western blot and Northern hybridization using UGT1A1 specific antibody and cDNA probe. Microsomal bilirubin UGT activity was also measured. The elevation of UGT1A1 mRNA was observed in the liver of ethanol consumer animals with the simultaneous increase in microsomal UGT1A1 protein leading to stimulated bilirubin glucuronidation both in vivo and in microsomal vesicles. These results arise the possibility of the transcriptional induction and/or the mRNA stabilization by ethanol consumption, which can be caused by ethanol itself or the metabolic changes due to the treatment.
Kardon
T
T
Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444, Budapest, Hungary.
Coffey
M J
MJ
Bánhegyi
G
G
Conley
A A
AA
Burchell
B
B
Mandl
J
J
Braun
L
L
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D014453:Glucuronosyltransferase; D001663:Bilirubin