Selenoprotein expression in the rat colon during Se deficiency.

Selenium is an essential trace element, which is present in several proteins, called seleneproteins, that have various biological roles

Selenoprotein gene expression in an intestinal cell line during selenium depletion: a macroarray approach indicates effects on SelW and glutathione peroxidise 1.

The micronutrient selenium (Se) is incoprprated into a renage of selenoproteins involved in numerous biochemical processes within the body

Differential effects of selenium and knock-down of glutathione peroxidases on TNFα and flagellin inflammatory responses in gut epithelial cells

Selenium (Se) is essential for human health. Despite evidence that Se intake affects inflammatory responses, the mechanisms by which Se and the selenoproteins modulate inflammatory signalling, especially in the gut, are not yet defined. The aim of this work was to assess effects of altered Se supply and knock-down of individual selenoproteins on NF-κB activation in gut epithelial cells. Caco-2 cells were stably transfected with gene constructs expressing luciferase linked either to three upstream NF-κB response elements and a TATA box or only a TATA box. TNFα and flagellin activated NF-κB-dependent luciferase activity and increased IL-8 expression. Se depletion decreased expression of glutathione peroxidase1 (GPX1) and selenoproteins H and W and increased TNFα-stimulated luciferase activity, endogenous IL-8 expression and reactive oxygen species (ROS) production. These effects were not mimicked by independent knock-down of either GPX1, selenoprotein H or W; indeed, GPX1 knock-down lowered TNFα-induced NF-κB activation and did not affect ROS levels. GPX4 knock-down decreased NF-κB activation by flagellin but not by TNFα. We hypothesise that Se depletion alters the pattern of expression of multiple selenoproteins that in turn increases ROS and modulates NF-κB activation in epithelial cells, but that the effect of GPX1 knock-down is ROS-independent

Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents

<p>Abstract</p> <p>Background</p> <p>Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency. These levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency. These levels, however, do not further increase with super-nutritional or toxic Se status, making them ineffective for detection of high Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial as well as adverse health outcomes. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with up to 5 μg Se/g diet.</p> <p>Results</p> <p>There was no effect of Se status on growth of mice fed 0 to 0.2 μg Se/g diet or rats fed 0 to 2 μg Se/g diet, but rats fed 5 μg Se/g diet showed a 23% decrease in growth and elevated plasma alanine aminotransferase activity, indicating Se toxicity. Rats fed 5 μg Se/g diet had significantly altered expression of 1193 liver transcripts, whereas mice or rats fed ≤ 2 μg Se/g diet had < 10 transcripts significantly altered relative to Se-adequate animals within an experiment. Functional analysis of genes altered by Se toxicity showed enrichment in cell movement/morphogenesis, extracellular matrix, and development/angiogenesis processes. Genes up-regulated by Se deficiency were targets of the stress response transcription factor, Nrf2. Multiple regression analysis of transcripts significantly altered by 2 μg Se/g and Se-deficient diets identified an 11-transcript biomarker panel that accounted for 99% of the variation in liver Se concentration over the full range from 0 to 5 μg Se/g diet.</p> <p>Conclusion</p> <p>This study shows that Se toxicity (5 μg Se/g diet) in rats vastly alters the liver transcriptome whereas Se-deficiency or high but non-toxic Se intake elicits relatively few changes. This is the first evidence that a vastly expanded number of transcriptional changes itself can be a biomarker of Se toxicity, and that identified transcripts can be used to develop molecular biomarker panels that accurately predict super-nutritional and toxic Se status.</p

Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes

Background: Selenium is incorporated into 25 selenoproteins in humans. Low dietary selenium has deleterious effects on health and may result in cancer, cardiovascular disease, and immune dysfunction. The underlying mechanisms are not fully understood. Lymphocytes are a target tissue; they can be assessed in healthy persons, and their response has not been explored by using global gene expression profiling techniques. Objectives: The objectives of the study were to assess the overall effect of selenium supplementation within a normal physiological range on the pattern of lymphocyte gene expression and to identify downstream processes affected by selenium intake. Design: Gene expression was assessed in lymphocytes isolated from 39 healthy persons before and after a 6-wk supplementation with 100 eta g Se/d as sodium selenite. Presupplementation and postsupplementation RNA samples from 16 subjects were chosen at random for microarray analysis. Differential gene expression was analyzed by using individual labeling and hybridization with human whole-genome microarrays. Array data were validated by quantitative real-time reverse transcriptase-polymerase chain reaction. Results: The study subjects had an average 19% increase in plasma selenium concentration, which was within a normal range. Fold changes in gene expression were small, but data analysis using biological process identification showed that selenium predominantly affected the genes that encode proteins functioning in protein biosynthesis. Gene expression changes were confirmed by quantitative polymerase chain reaction for 3 representative target genes (RPL37A, RPL30, and EEF1E1). Conclusions: Ribosomal protein and translation factor genes were up-regulated in response to increased selenium intake. We hypothesize that this up-regulation is linked to increased selenoprotein production and enhanced lymphocyte function

Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes

Background: Selenium is incorporated into 25 selenoproteins in humans. Low dietary selenium has deleterious effects on health and may result in cancer, cardiovascular disease, and immune dysfunction. The underlying mechanisms are not fully understood. Lymphocytes are a target tissue; they can be assessed in healthy persons, and their response has not been explored by using global gene expression profiling techniques. Objectives: The objectives of the study were to assess the overall effect of selenium supplementation within a normal physiological range on the pattern of lymphocyte gene expression and to identify downstream processes affected by selenium intake. Design: Gene expression was assessed in lymphocytes isolated from 39 healthy persons before and after a 6-wk supplementation with 100 eta g Se/d as sodium selenite. Presupplementation and postsupplementation RNA samples from 16 subjects were chosen at random for microarray analysis. Differential gene expression was analyzed by using individual labeling and hybridization with human whole-genome microarrays. Array data were validated by quantitative real-time reverse transcriptase-polymerase chain reaction. Results: The study subjects had an average 19% increase in plasma selenium concentration, which was within a normal range. Fold changes in gene expression were small, but data analysis using biological process identification showed that selenium predominantly affected the genes that encode proteins functioning in protein biosynthesis. Gene expression changes were confirmed by quantitative polymerase chain reaction for 3 representative target genes (RPL37A, RPL30, and EEF1E1). Conclusions: Ribosomal protein and translation factor genes were up-regulated in response to increased selenium intake. We hypothesize that this up-regulation is linked to increased selenoprotein production and enhanced lymphocyte function