Effect of selenium and vitamin E deficiency on differential gene expression in rat liver.
To examine the molecular events associated with selenium (Se) and vitamin E (VE) deficiency, we applied cDNA array technology to define the transcriptional response in the liver of Se- and VE-deficient rats. VE deficiency alone did not induce any significant changes in expression profile among the genes evaluated. Se deficiency lead to a down-regulation of Se-dependent cGPx and to an induction of genes, encoding for detoxifying enzymes in liver (cytochrome P450 4B1, UDP-glucuronosyltransferase 1). Combined VE and Se deficiency was characterized by alterations in the expression level of genes encoding for proteins involved in inflammation (multispecific organic anion exporter, SPI-3 serine protease inhibitor) and acute phase response (alpha-1 acid glycoprotein, metallothionein 1). Additionally, a significant down-regulation in the expression level of genes important in the inhibition of apoptosis (defender against cell death 1 protein, Bcl2-L1), cell cycle (G1/S-specific cyclin D1) and antioxidant defense (gamma-glutamylcysteine synthetase catalytic subunit) was demonstrated. The experimental strategy identified several novel Se and VE sensitive genes.
Fischer
A
A
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University, 35392 Giessen, Germany.
Pallauf
J
J
Gohil
K
K
Weber
S U
SU
Packer
L
L
Rimbach
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001189:Aryl Hydrocarbon Hydroxylases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics; D008058:Dihydrolipoamide Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D004790:Enzyme Induction; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D012643:Selenium / Q000172:deficiency* / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism*
D017392:Thiobarbituric Acid Reactive Substances; D019715:Tissue Inhibitor of Metalloproteinase-1; D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System; D008668:Metallothionein; D005979:Glutathione Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1; D008058:Dihydrolipoamide Dehydrogenase; D014453:Glucuronosyltransferase; D005978:Glutathione; D012643:Selenium