Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to limited selenium intake in mouse colon
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ABSTRACT:
PROVIDER: PRJNA480871 | ENA |
REPOSITORIES: ENA
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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:Moderate selenium deficiency may lead to an impaired capacity to cope with health challenges. Functional effects of suboptimal selenium intake are not fully known, and biomarkers for an insufficient selenium supply are inadequate. We therefore fed mice diets of moderately deficient or adequate selenium intake for 6 weeks. Changes in global gene expression were monitored by microarray analysis in splenic leukocytes. Genes for four selenoproteins, Sepw1, Gpx1, Selh and Sep15, were the most significantly down-regulated in moderate selenium deficiency, and this was confirmed by quantitative polymerase chain reaction (qPCR). Classification of significantly affected genes revealed that processes related to inflammation, heme biosynthesis, DNA replication and transcription, cell cycle and transport were affected by selenium restriction. Down-regulation by moderate selenium deficiency of specific genes involved in inflammation and heme biosynthesis was confirmed by qPCR. Myeloperoxidase and lysozyme activities were decreased in selenium-restricted leukocytes, providing evidence for functional consequences. Genes for 31 nuclear factor (NF)-κB targets were down-regulated in moderate selenium deficiency, indicating an impaired NF-κB signaling. Together, the observed changes point to a disturbance in inflammatory response. The selenoproteins found here to be sensitive to selenium intake in murine leukocytes might also be useful as biomarkers for a moderate selenium deficiency in humans.
2018-07-13 | GSE117026 | GEO
Project description:Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis and prevents unrestrained (phospho)lipid peroxidation by directly reducing phospholipid hydroperoxides (PLOOH) to their corresponding alcohols. However, it remains unclear whether other phospholipid peroxidases can also contribute to ferroptosis prevention, albeit to a varying degree. Here we show that cells lacking GPX4 still exhibit substantial PLOOH reduction capacity, arguing for the presence of alternative PLOOH peroxidases. Mechanistically, we uncover that PRDX6 facilitates intracellular selenium handling, which is crucial for selenium incorporation into selenoproteins, including GPX4.
2025-01-14 | PXD056040 | Pride
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: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: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:Role of Selenium Intake for Risk and Development of Graves’ Disease
| PRJNA473976 | ENA
Project description:We tested the hypothesis that the behavioral response to selenium (Se) follows a hormetic dose response pattern, manifested through the functions of selenoproteins within the brain. We measured anxiety-related behaviors in zebrafish (Danio rerio) at deficient, control and supplemented levels of dietary Se, and measured the transcriptional response of selenoprotein genes important for neuroprotection. We also used a microarray approach to assess the transcriptomic response of the midbrain to Se. The behavioral response to Se was characterized by hormesis, and the direction, magnitude, and shape of the hormetic responses were dependent on both sex and zebrafish population. Transcription of selenoproteins within the midbrain also responded to Se in a similar hormetic dose-dependent manner, with sex and population influencing the trajectory of the responses. The hormetic behavioral response to Se may therefore be manifested through selenoproteins in the brain, but the influence is not direct.
2014-05-01 | GSE52484 | GEO
Project description:The synthesis mechanisms and function evaluation of selenium(Se)-enriched microorganism remain relatively unexplored. We here report the Se biotransformation by A. oryzae A02. Comparative RNA-Seq analysis revealed the upregulation of functional genes implicated in selenium transformation, activating multiple potential pathways for selenium reduction. The assimilatory and dissimilatory reductions of Se oxyanions engaged numerous parallel and interconnected pathways, manifesting a harmonious equilibrium in overall Se biotransformation in A. oryzae A02.
2024-07-07 | GSE270867 | GEO
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