Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE23895 | GEO | 2011/01/19
SECONDARY ACCESSION(S): PRJNA130445
REPOSITORIES: GEO
Similar Datasets
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:The trace element selenium (Se) plays an important role in thyroid hormone metabolism. Low Se intake is associated with atuoimmune hypothyroidism. The interaction of Se and Graves’ disease (GD) is only poorly characterized. We have investigated the importance of dietary Se supply for GD by performing a more in-depth analysis of a large cross-sectional study of 6152 participants from two counties within the Shaanxi Province, China, which are characterized by different habitual Se intakes, and studied the effects of different dietary Se supply (0.02, 0.18, 0.6 or 2.0 ppm Se) on disease development in a mouse model of GD. In the cross-sectional study, prevalence of GD in the two areas of different Se intake was similar, and the Se status of GD patients was not different from healthy control subjects. The dietary Se supply in the animal model was not affecting thyroid hormone levels, malondialdehyde concentrations, total antioxidant capacity or the titer of GD-causing TSH receptor autoantibodies (TRAb). Expression analysis of transcripts in spleen indicated regulatory effects of Se intake on genes implicated in the immune response, erythropoiesis and oxygen status. However, the humoral immune response including the ratio of CD4/CD8 or Th1/Th2 cells, and the concentration of Treg cells were similar between the experimental groups despite their varying Se intakes. Our data from both the epidemiological analysis and animal experiment do not indicate a major role of Se in the development of GD, and highlight that autoimmune hypothyroidism and GD differ in their relation to Se status.
2021-05-30 | GSE115152 | GEO
Project description:Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086mg Se/kg) or a selenium-adequate (0.15mg Se/kg) diet. After 6wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status.
2018-07-13 | GSE117025 | GEO
Project description:Transcriptomics and proteomics analyses were carried out on rectal mucosal biopsies from 22 healthy adults with either optimal (n=11, mean plasma Se =1.43μmol/l, s.e.m ±0.06) or sub-optimal (n=11, mean plasma Se = 0.86umol/l, s.e.m ± 0.01) plasma Se status. Plasma Se status was associated with altered expression of 254 genes implicated in cancer, immune function and inflammatory response, cell growth and proliferation, cellular movement and cell death; 69 out of 254 genes had their expression significantly correlated with Se status, including two selenoprotein genes (SEPW1 and SELK). Proteomics identified 26 proteins differentially expressed between the two Se groups, including cytoskeletal proteins and factors involved in immune and inflammatory response and cancer pathways. Results from proteomics and transcriptomics support each other and integration of the two datasets was consistent with a reduced inflammatory and immune responses and a cytoskeleton remodelling in the rectal mucosa of individuals with sub-optimal Se status.
2015-12-31 | GSE70550 | GEO
Project description:Interventions: 30 healthy volunteers (>50yrs) at-risk for CRC by virtue of age and /or other standard risk factors will be recruited to participate in a randomised, three cohort dietary intervention study. with a parallel design to test the effects of Se and green tea alone and in combination on molecular biomarkers for CRC prevention in the normal rectal epithelial cells. They will be instructed to maintain their usual diet during the study but to avoid supplementation with any green tea-related food or drink (limited to <3 cups of black tea per day), and Se-rich foods such as octopus, crab and tuna, liver and kidney or additional Brazil nuts or other nuts (except those Brazil nuts and green tea extract prescribed by us). The study will consist of dietary intervention period of 6 weeks, preceded by a run in period of 4 weeks.
The volunteers will be randomised (randomisation will be computer generated) into one of three groups of 10, receiving
1) Se, supplied as Brazil nuts (6 Brazil nuts daily will provide 48micrograms Se/day);
2) Green tea, supplied as a green tea extract capsule (4 capsules daily will provide 800mg EGCG/day); and
3) Se + green tea (6 Brazil nuts daily + 4 green tea extract capsules daily (will provide 48micrograms Se/day and 800mg EGCG/day).
Six Brazil nuts has been chosen because the average Se concentration (2.7 micrograms Se/g) in Brazil nuts (supplied from Charlesworth, Australia) is relatively low compared to that of the report by Thomson et al, where the Se concentration is 6.4micrograms Se/g, and average weight for one nut is 4g, 2 nuts provided 53 micrograms Se/day (Am J Clin Nutr 2008;87:379-3840). Since the average weight of one Brazil nut (supplied from Charlesworth, Australia) is 3g, 6 Brazil nuts daily will provide 48microgra
Primary outcome(s): Effects of combination diet (Se + green tea) on biomarkers of Wnt pathway (catenin), inflammation (COX-2) and DNA repair (MGMT) in rectal epithelium. Rectal biopsies will be collected and examined by RT-PCR and immunohistochemistry for the expression of these biomarkers at gene and protein levels[Commencement of Intervention (Baseline),
End of intervention (6 weeks) ]
Study Design: Purpose: Prevention; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy
| 2459098 | ecrin-mdr-crc
Project description:Selenium (Se) is an essential trace element for human and animal health. Se fertilizer has been used to increase the Se content in crops to meet the Se requirements in humans and animals. To address the challenge of Se poisoning in plants, the mechanisms underlying Se-induced stress in plants must be understood. Here, to elucidate the effects of Se stress on the protein levels in pepper, we used an integrated approach involving tandem mass tag labeling, HPLC fractionation, and mass spectrometry-based analysis. A total of 4,693 proteins were identified, 3,938 of which yielded quantitative information. Among them, the expression of 172 proteins was up-regulated, and the expression of 28 proteins was down-regulated in the Se/mock treatment comparison. According to the above data, we performed a systematic bioinformatics analysis of all identified proteins and differentially expressed proteins (DEPs). The DEPs were most strongly associated with the terms ‘metabolic process’, ‘posttranslational modification, protein turnover, chaperones,’ and ‘protein processing in endoplasmic reticulum’ according to GO, KOG classification, and KEGG enrichment analysis, respectively. Furthermore, several heat shock proteins were identified as DEPs. These results provide insights that may facilitate further studies on the pepper proteome expressed downstream of the Se stress response. Our data revealed that the responses of pepper to Se stress involve various pathways.
2019-09-16 | PXD013257 | Pride
Project description:miRNA array comparing the transcription profile of control rats and rats after intra-hippocampal pilocarpine-induced Status Epilepticus (PILO-SE).
2016-04-28 | E-MTAB-4633 | biostudies-arrayexpress
Project description:Interventions: Participants will take 6 brazil nuts a day for four weeks.
This four week intervention will be preceded by a 4 week run-in / wash out phase
participants will be advised to exclude any selenium rich foods or green tea during the study
This Pilot study will confirm the amount of Brazil Nuts we will use in the study comparing with green tea. This follow up study (Effects of combining Selenium (Se) and green tea on biomarkers for colorectal cancer prevention in human subjects). will be registered with ANZCTR in the near future’
At the initial interview dietary advice will be given. This will give an understanding of the nature of the volunteers diet and the likely influence of Se to the diet and suitability to become involved in the study
(if intolerant to nuts volunteers will not participate in the study)
We will ask participants not to consume, whenever possible, throughout the study:-
Any selenium supplement
Any selenium enriched foods, such as nuts, sea food (such as tuna or octopus)
The Brazil nut is a large nut that comes from the castanheiro de para tree in Brazil’s rainforests. Each serving of about six to eight nuts contains 4 g of protein and 7 grams each of monosaturated and polysaturated fat.
Brazil nuts (Berholletia excelas, family Lecythidaceae) are the richest known food source of selenium, with mean concentrations reported in the literature between 8-83 micrograms Se/g
6 Brazil nuts daily provides 48 micrograms Se/day - 53 micrograms Se/day
Primary outcome(s): If supplementation of 6 Brazil nuts/day increases plasma Selenium (Se) levels
A blood sample (5mls of whole blood taken on 2 occasions) will be collected at baseline and after intervention, testing for plasma Selenium levels[Blood samples collected at commencement of intervention (week 0) and at end of intervention (wk 4)]
Study Design: Purpose: Prevention; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety
| 2458510 | ecrin-mdr-crc
Project description:Trace element selenium (Se) is incorporated as the 21st amino acid, selenocysteine (Sec), into selenoproteins through tRNA[Ser]Sec. Selenoproteins act as gatekeepers of redox homeostasis and modulate immune function to effect anti-inflammation and resolution. However, mechanistic underpinnings involving metabolic reprogramming during inflammation and resolution remain poorly understood. Endotoxin lipopolysaccharide (LPS) activation of murine bone marrow-derived macrophages (BMDMs) cultured in the presence or absence of Se (as selenite) was used to examine temporal changes in the proteome and metabolome by multiplexed tandem mass tag-quantitative proteomics, metabolomics, and machine-learning approaches. Se-dependent modulation of glycolytic, TCA and PPP pathways predisposed BMDMs to preferentially increase OXPHOS to efficiently regulate inflammation and its timely resolution. Use of macrophages lacking selenoproteins, indicated that all three metabolic nodes were sensitive to selenoproteome expression. Furthermore, inhibition of SDH with dimethylmalonate affected the pro-resolving effects of Se by increasing the resolution interval in a murine peritonitis model.
2021-02-09 | PXD023005 | Pride
Project description:Mice were fed Se-deficient or Se-adequate diets for 6 weeks. Liver and lung tissue were harvested and processed for RNA-Seq, ribosome profiling, and microarray analysis. From these studies, we identified changes in mRNA levels and translation of selenoprotein genes and genes regulated by interferon-gamma. Cytokine profiles of serum indicated that interferon-gamma and IL-6 levels were increased in the Se-adequate mice relative to Se-deficient mice. Gene expression analysis of liver and lung tissue from mice fed Se-deficient or Se-adequate diets
2015-08-06 | E-GEOD-71716 | biostudies-arrayexpress