Glucose inhibition of the induction of CYP2E1 mRNA expression by ethanol in FGC-4 cells.
1. Rats fed intragastrically with ethanol-containing diets made with low levels of carbohydrates have greater CYP2E1 induction than rats fed similar diets made with high carbohydrate levels. 2. FGC-4 rat hepatoma cells were used to test the hypothesis that carbohydrates could down-regulate ethanol-induced CYP2E1 induction. 3. FGC-4 cells grown in a glucose-free media and treated with 1-100 mM ethanol for 24 h exhibited a dose-dependent increase (p < 0.05) in CYP2E1, with maximum mRNA steady-state (3.8-fold) or protein (3.1-fold) levels measured at 30 or 100 mM ethanol, respectively. 4. In cells treated with 30 mM ethanol, a glucose concentration-dependent inhibition (p < 0.05) of CYP2E1 mRNA was observed between 2.5 and 10 mM glucose. 5. Induction by 30 mM ethanol of CYP2E1 protein was reduced in cells co-treated with 1 mM or greater glucose concentration and complete inhibition was measured with 5 mM glucose co-treatment. 6. These data demonstrate that under culture conditions of extremely low carbohydrate concentrations: (1) ethanol treatment of FGC-4 cells results in elevated steady-state levels of CYP2E1 mRNA and protein; and (2) glucose inhibits this increase. 7. It is concluded that glucose can negatively regulate CYP2E1 expression and could at least partially explain the greater induction of hepatic CYP2E1 in rats fed low carbohydrate ethanol-containing diets compared with high carbohydrate diets at the same ethanol level.
Arkansas Children' Nutrition Center and Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. badgerthomasm@uams.edu
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D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis* / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007202:Indicators and Reagents; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007202:Indicators and Reagents; D012333:RNA, Messenger; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D005947:Glucose