Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents
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PROVIDER: PRJNA130445 | ENA |
REPOSITORIES: ENA
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Project description:Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency. Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 µg Se/g diet. Rats or mice were fed Se-deficient diets supplemented with sodium selenite up to 5 ug Se/g diet for 28 or 35 days. Affymetrix Rat 230 2.0 and Mouse 430 2.0 Genome Arrays were used to analyze gene expression in liver in all studies plus kidney in the mouse study.
2011-01-19 | E-GEOD-23895 | biostudies-arrayexpress
Project description:Protein and mRNA levels for several selenoproteins, such as glutathione peroxidase-1 (Gpx1), are down-regulated dramatically by selenium (Se) deficiency. Selenoprotein levels in rats increase sigmoidally with increasing dietary Se and reach defined plateaus at the Se requirement, making them sensitive biomarkers for Se deficiency, but not high for Se status. Biomarkers for high Se status are needed as super-nutritional Se intakes are associated with beneficial and adverse health outcomes, but conventional biomarkers are not especially useful above the Se requirement. To characterize Se regulation of the transcriptome, we conducted 3 microarray experiments in weanling mice and rats fed Se-deficient diets supplemented with levels of Se up to 5 µg Se/g diet.
2011-01-19 | GSE23895 | GEO
Project description:BackgroundProtein 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.ResultsThere 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.ConclusionThis 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.
| S-EPMC3032699 | biostudies-literature
Project description:Methylmercury (MeHg) is a well-known neurotoxicant, particularly harmful for the developing brain. Selenium is a nutrient previously shown to interact with MeHg, however the molecular mechanisms behind these interaction is not fully described. To explore the effect of selenium on MeHg, mice were exposed to selenomethionine (SeMet) and MeHg in a 2 x 3 full factorial design for 12 weeks. After termination, organs, including the brain, were collected for Hg and Se analysis. The hippocampus was collected and analysed using gel free proteomics and RNA sequencing (RNA-seq). The presence of SeMet reduced the amount of Hg in several organs, including the brain, while the level of Hg were increased in the feces. The presence of Hg also increased the concentration of selenium in liver and cortex. Proteomic and RNA-seq analyses showed that several known pathways of MeHg toxicity, such as oxidative stress, altered metabolism and calcium disruption were alleviated when SeMet were present. Our results suggest that SeMet can to a certain extent ameliorate the neurotoxic effects of MeHg in a mouse model. Although, whether this is due to decrease of body burden of Hg or through direct interactions with selenium in vivo remains unclear.
2020-08-29 | GSE135381 | GEO
Project description:Determine whether nutritional support with high protein ONS in adult oncologic patients in the first step of cancer cachexia - asymptomatic precachexia, influence on the toxicity of systemic therapy.
| 2221014 | ecrin-mdr-crc
Project description:Methanococcus maripaludis utilizes selenocysteine-(Sec-) containing proteins (selenoproteins), mostly active in the organism’s primary energy metabolism, methanogenesis. Under selenium depletion, M. maripaludis employs a set of enzymes containing cysteine (Cys) instead of Sec. The genes coding for these Sec-/Cys-containing isoforms are the only genes known expression of which is influenced by the selenium status of the cell. Using quantitative proteomics and transcriptomics approx. 7% and 12%, respectively, of all genes/proteins were differentially expressed/synthesized in response to the selenium supply. Some of the genes identified involve methanogenesis, nitrogenase functions, and putative transporters. An increase of transcript abundance for putative transporters under selenium-depleted conditions indicated the organism’s effort to tap into alternative sources of selenium. Selenium sources M. maripaludis is known to utilize are selenite and dimethylselenide. To expand this list, a selenium responsive reporter strain was assessed with nine other, environmentally relevant selenium species. While some had a similar biological window as selenite, others were effectively utilized at lower concentrations. Conversely, selenate and seleno-amino acids were only utilized at unphysiologically high concentrations and two compounds were not utilized at all. To address the role of the selenium-regulated putative transporters in selenium transport, M. maripaludis mutant strains lacking one or two of the putative transporters were tested for the capability to utilize the different selenium species. Of the five putative transporters analyzed by loss-of-function mutagenesis, none appeared to be absolutely required for utilizing any of the selenium species tested, indicating they have redundant and/or overlapping specificities, or are not dedicated selenium transporters.
2024-03-27 | PXD047095 | Pride
Project description:We studied the application of transcriptome technology in alfalfa selenium treatment. After spraying sodium selenite on the leaves, the process of selenium absorption and assimilation of alfalfa is unknown. The time point of transcriptome determination was determined by measuring the change of selenium content. Our results showed that 12 h was the key point of the change of selenium content in alfalfa, that is, the selenium content increased continuously before 12 h, decreased gradually after 12 h, and remained stable after 48 h. Transcriptome sequencing showed that phosphorus transporter and endocytosis related genes may be involved in selenium absorption at 12 h compared with 0 H. 12-48 h, some thiometabolic pathways may be involved in selenium metabolism and ubiquitination pathway, which may be the detoxification pathway of selenoprotein.
2024-10-27 | GSE186868 | GEO
Project description:Background & aim: Micronutrient deficiencies, particularly those of zinc and selenium, are common in persons living with human immunodeficiency virus (PLWHIV), and have been associated with the development of non-AIDS related comorbidities, impaired immune system function, HIV disease progression and mortality. The implementation of intervention strategies on clinically stable long-term-treated PLWHIV could bring potential benefits on impeding or delaying the onset of non-AIDS associated comorbidities, improving their health status and overall quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density (BMD), lipids profile, glucose and immune system activation and function on PLWHIV on antiretroviral therapy (ART) without metabolic diseases. Methods: This pilot trial was composed of 60 PLWHIV on ART who were randomly assigned to either zinc, selenium, zinc + selenium supplementation or to a control group. Daily supplementation was prescribed during 6 months as follows: the zinc group received 30 mg of zinc gluconate, the selenium group received 200 mcg of selenium yeast and the zinc + selenium group received both micronutrients at the same doses and presentations. Individuals in the control group were followed during the same time without any nutritional supplementation. Body composition (weight, body mass index [BMI], fat mass and muscle mass), BMD, blood pressure, blood biochemical parameters (cholesterol, glucose and triglycerides), serum zinc and selenium concentrations, CD4+ T cell count and CD4+ and CD8+ T cells immune activation were assessed before and after supplementation. One individual of each supplementation group and one of the control group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p=0.03), fat mass in kg (p=0.03) and percentage (p=0.02), as well as trunk fat (p=0.01), were significantly decreased after selenium supplementation. No changes were observed for body composition, BMD, biochemical determinations or blood pressure on the other intervention groups after supplementation (p>0.05 in all cases). The CD4+ T cells frequency and count significantly increased after selenium and zinc supplementation (p=0.03, p=0.05 respectively). CD4+ and CD8+ T-cell immune activation did not change after supplementation (p>0.05 in both cases). On the single cell transcriptome analysis, zinc and selenium supplementation significantly change de expression of genes associated with the function of naive and memory CD8+ T cells (adjusted p<0.05 in all cases). Conclusions: Selenium supplementation have beneficial effects on the body composition, while zinc and selenium supplementation increased CD4+ T cell replenishment of PLWHIV on long-term ART without metabolic diseases. Additionally, zinc and selenium supplementation modified the expression of genes associated with the function of naive and memory CD8+ T cells. Zinc and selenium supplementation are a simple, low-cost, and safe nutritional treatment that represents a complementary intervention to improve the health status and increase the quality of life of clinically stable PLWHIV without metabolic diseases. Registered: Under ClinicalTrails.gov identifier NCT03421314
2024-09-06 | GSE253497 | GEO