Modulation of hepatic gene expression by alpha-tocopherol in cultured cells and in vivo.
To obtain a comprehensive understanding of the molecular mechanisms of action of vitamin E (VE), global gene expression profiles using DNA arrays in rat liver and hepatocellular liver carcinoma cells (HepG2) were obtained. For the analysis of short-term (49 days) and long-term (290 days) VE deficiency, rats were fed semisynthetic diets either supplemented with or deficient in VE. In addition, HepG2 cells were treated with VE concentrations comparable to those that were achieved in the in vivo experiment. Differential gene expression in rat liver and that in HepG2 cells were measured by DNA arrays comprising up to 7,000 genes. Dietary VE deficiency over a 7-week period did not induce any significant changes in the expression profile among the genes evaluated. However, long-term VE deficiency upregulated coagulation factor IX (FIX), 5-alpha-steroid reductase type 1, and CD36 mRNA levels. Furthermore, VE deficiency resulted in a significant downregulation of hepatic gamma-glutamyl-cysteinyl synthetase, the rate-limiting enzyme of glutathione synthesis. According to the rat experiment, VE supplementation changed coagulation factor IX and CD36 expression in HepG2 cells; thus, in vivo data could be partly confirmed with the in vitro model. Overall, the current studies reveal that dietary VE has important long-term effects on liver gene expression with potential downstream effects on extrahepatic tissues.
Rimbach
Gerald
G
Institute of Human Nutrition and Food Science, Olshausenstrasse 40, D-24118 Kiel, Germany. rimbach@foodsci.uni-kiel.de
Fischer
Alexandra
A
Stoecklin
Elisabeth
E
Barella
Luca
L
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000494:pharmacology*
D024502:alpha-Tocopherol