Transcriptional induction of bilirubin UDP-glucuronosyltransrase by ethanol in rat liver

Kardon, Tamás; Coffey, Marcus Jonathan; Bánhegyi, Gábor; Conley, Abigail Ann; Burchell, Brian; Mandl, József; Braun, László

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Volume 21, Issue 3 , Pages 251-257, July 2000

Transcriptional induction of bilirubin UDP-glucuronosyltransrase by ethanol in rat liver

Tamás Kardon
- Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary
Marcus Jonathan Coffey
- Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
Gábor Bánhegyi
- Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary
Abigail Ann Conley
- Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
Brian Burchell
- Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
József Mandl
- Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary
- Corresponding author. Tel.: +36-1-266-26-15; fax: +36-1-266-26-15
László Braun
- Department of Medical Chemistry, Semmelweis University of Medicine, P.O. Box 260, H-1444 Budapest, Hungary

Received 7 May 1999; received in revised form 18 January 2000; accepted 10 April 2000.

Abstract

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.

Keywords: Ethanol, Bilirubin, Glucuronidation, Liver