Abstract
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.
Copyright 2001 Academic Press.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Aryl Hydrocarbon Hydroxylases*
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Cell Cycle / drug effects
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Cell Cycle / physiology
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Cytochrome P-450 Enzyme System / biosynthesis
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Cytochrome P-450 Enzyme System / genetics
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Dihydrolipoamide Dehydrogenase / biosynthesis
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Dihydrolipoamide Dehydrogenase / genetics
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Enzyme Induction
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Glucuronosyltransferase / biosynthesis
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Glucuronosyltransferase / genetics
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Glutathione / metabolism
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Glutathione Peroxidase / biosynthesis
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Glutathione Peroxidase / genetics*
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Liver / cytology
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Liver / drug effects
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Liver / physiology*
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Metallothionein / metabolism
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Rats
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Selenium / deficiency*
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Selenium / pharmacology
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Thiobarbituric Acid Reactive Substances / metabolism
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Tissue Inhibitor of Metalloproteinase-1 / genetics
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Vitamin E / pharmacology*
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Vitamin E Deficiency / metabolism*
Substances
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Thiobarbituric Acid Reactive Substances
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Tissue Inhibitor of Metalloproteinase-1
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Vitamin E
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Cytochrome P-450 Enzyme System
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Metallothionein
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Glutathione Peroxidase
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Aryl Hydrocarbon Hydroxylases
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cytochrome P-450 CYP4B1
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Dihydrolipoamide Dehydrogenase
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Glucuronosyltransferase
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Glutathione
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Selenium