Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply.
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ABSTRACT:
SUBMITTER: Schweizer U
PROVIDER: S-EPMC1134785 | biostudies-other | 2005 Mar
REPOSITORIES: biostudies-other
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Project description:Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key role in selenium (Se) transport throughout the body. Development of a Sel P knockout mouse model has supported this notion and initial studies have indicated that selenium supply to various tissues is differentially affected by genetic deletion of Sel P. Se in the form of the amino acid, selenocysteine, is incorporated into selenoproteins at UGA codons. Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in mice affected levels of the mRNAs encoding all known members of the murine selenoprotein family, as well as three non-selenoprotein factors involved in their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2 (SBP2) and SECp43. Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes. We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.
| S-EPMC1919489 | biostudies-literature
Project description:Selenium is an essential dietary micronutrient. Ingested selenium is absorbed by the intestines and transported to the liver where it is mostly metabolized to selenocysteine (Sec). Sec is then incorporated into selenoproteins, including selenoprotein P (SELENOP), which is secreted into plasma and serves as a source of selenium to other tissues of the body. Herein, we provide an overview of the biology of selenium from its absorption and distribution to selenoprotein uptake and degradation, with a particular focus on the latter. Molecular mechanisms of selenoprotein degradation include the lysosome-mediated pathway for SELENOP and endoplasmic reticulum-mediated degradation of selenoproteins via ubiquitin-activated proteasomal pathways. Ubiquitin-activated pathways targeting full-length selenoproteins include the peroxisome proliferator-activated receptor gamma-dependent pathway and substrate-dependent ubiquitination. An alternate mechanism is utilized for truncated selenoproteins, in which cullin-RING E3 ubiquitin ligase 2 targets the defective proteins for ubiquitin-proteasomal degradation. Selenoproteins, particularly SELENOP, may have their Sec residues reutilized for new selenoprotein synthesis via Sec decomposition. This review will explore these aspects in selenium biology, providing insights to knowledge gaps that remain to be uncovered.
| S-EPMC6801053 | biostudies-literature
Project description:BackgroundWe examined the relationship between brain-derived neurotrophic factor (BDNF) and chronic kidney disease (CKD).MethodsFirst, a cross-sectional study was conducted in 480 participants without known diabetes. An oral glucose tolerance test (OGTT) was administered after overnight fasting, and blood samples were collected at 0, 30, and 120 min. Second, a total of 3003 participants were enrolled for the case-control genetic analysis. After assigning them to a case or a control group based on age and CKD status, we investigated the association between BDNF gene variants and susceptibility to CKD.ResultsA higher fasting serum BDNF quartile was significantly associated with a lower prevalence of CKD (P value for trend < 0.001). Based on the receiver operating characteristic analysis, the fasting BDNF level had a larger area under the curve for differentiating CKD (0.645, 95% CI 0.583‒0.707) than the BDNF levels at both 30 min (0.547, 95% CI 0.481‒0.612) and 120 min (0.598, 95% CI 0.536‒0.661). A significantly lower CKD prevalence (odds ratio = 0.30, 95% CI 0.12‒0.71) was observed in the highest quartile of fasting BDNF level than that in the lowest quartile, whereas no interquartile differences were observed for BDNF levels determined at 30 or 120 min during the OGTT. Furthermore, BDNF-associated variants, including rs12098908, rs12577517, and rs72891405, were significantly associated with CKD.ConclusionsThe BDNF level at fasting, but not at 30 and 120 min after glucose intake, was an independent indicator of CKD. In addition, significant associations were observed between three BDNF gene variants and CKD.
| S-EPMC9926783 | biostudies-literature
Project description:How is the essential micronutrient, selenium (Se), transported in the serum and then donated to tissues? In this issue of the Biochemical Journal, Schweizer and colleagues demonstrate, using conditional and total mouse knockout models, that SePP (selenoprotein P) is the major transporter of Se in the serum. Moreover, in the sanctuary area of the brain, SePP was shown to play a hitherto unexpected role as a local Se storage and recycling protein that directly maintains brain Se levels. Considering the function of Se in normal brain metabolism, these results are crucial for our understanding of the role of selenoproteins in redox regulation, antioxidant defences, thyroid hormone metabolism and the development of neurodegenerative conditions.
| S-EPMC1134806 | biostudies-other
Project description:Changes of Selenoprotein F (SELENOF) protein levels have been reported during selenium supplementation, stressful, and pathological conditions. However, the mechanisms of how these external factors regulate SELENOF gene expression are largely unknown. In this study, HEK293T cells were chosen as an in vitro model. The 5'-flanking regions of SELENOF were analyzed for promoter features. Dual-Glo Luciferase assays were used to detect promoter activities. Putative binding sites of Heat Shock Factor 1 (HSF1) were predicted in silico and the associations were further proved by chromatin immunoprecipitation (ChIP) assay. Selenate and tunicamycin (Tm) treatment were used to induce SELENOF up-regulation. The fold changes in SELENOF expression and other relative proteins were analyzed by Q-PCR and western blot. Our results showed that selenate and Tm treatment up-regulated SELENOF at mRNA and protein levels. SELENOF 5'-flanking regions from -818 to -248 were identified as core positive regulatory element regions. Four putative HSF1 binding sites were predicted in regions from -1430 to -248, and six out of seven primers detected positive results in ChIP assay. HSF1 over-expression and heat shock activation increased the promoter activities, and mRNA and protein levels of SELENOF. Over-expression and knockdown of HSF1 showed transcriptional regulation effects on SELENOF during selenate and Tm treatment. In conclusion, HSF1 was discovered as one of the transcription factors that were associated with SELENOF 5'-flanking regions and mediated the up-regulation of SELENOF during selenate and Tm treatment. Our work has provided experimental data for the molecular mechanism of SELENOF gene regulation, as well as uncovered the involvement of HSF1 in selenotranscriptomic for the first time.
| S-EPMC6562903 | biostudies-literature
Project description:The most commonly used methods for assessing the selenium (Se) status in humans involve analysis of Se concentration, selenoprotein activity, and concentration in the blood and its compartments. Recently, it has been suggested that the expression of selenoprotein mRNA in circulating blood leukocytes could differently reflect Se status, due to prioritization of specific selenoprotein synthesis in response to dietary Se supply. Whereas the Se levels required for optimization of selenoprotein P level and plasma glutathione peroxidise activity are well known, estimation of Se level that is required for maximal mRNA expression of selenoprotein in humans is the subject of current investigations. Studies on rats suggest that whole blood selenoprotein mRNA level can be used as the relevant molecular biomarker for assessing Se status, and suboptimal Se intake may be sufficient to achieve effective expression. Human studies, however, did not confirm this hypothesis. According to studies on rodents and humans discussed in this review, it appears that suboptimal Se intake may be sufficient to satisfy molecular requirements of Se and it is lower than current recommended dietary intake in humans. The use of selenoprotein transcripts as a molecular biomarker of Se status requires further studies on a large group of healthy individuals with different baseline Se, including data regarding genetic polymorphism of selenoproteins and data regarding potential modifiers of Se metabolism.
| S-EPMC3316749 | biostudies-literature
Project description:The current NRC selenium (Se) requirement for turkeys is 0.2 μg Se/g diet. We previously fed turkey poults a Se-deficient diet (0.005 μg Se/g) supplemented with 10 graded levels of Se (0, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1.0 μg Se/g as Na2SeO3, 5/treatment) for 4 wk, and found that the minimum dietary Se requirement was 0.3 μg Se/g based on selenoprotein enzyme activity in blood, liver, gizzard and pancreas. Because the turkey is primarily a production animal, we expanded this analysis to kidney, heart, breast and thigh. Se concentrations in Se-deficient poults were 5.0, 9.8, 33, and 15% of levels in poults fed 0.4 μg Se/g in liver, kidney, thigh and breast, respectively. Increasing Se supplementation resulted in hyperbolic response curves for all tissues; breakpoint analysis indicated minimum Se requirements of 0.34-0.36 μg Se/g based on tissue Se levels in liver, kidney and thigh. Similarly, GPX1 activity in muscle tissues and kidney responded hyperbolically to increasing dietary Se, reaching well-defined plateaus with breakpoints at 0.30-0.36 μg Se/g. Minimum Se requirements based on GPX4 activity were 0.30-0.32 μg Se/g for breast and thigh. Selenoprotein transcript expression decreased significantly in Se deficiency for only 2, 3, 5, and 6 mRNA in breast, thigh, heart, and kidney, respectively, out of 24 known avian selenoproteins. Se response curves for regulated selenoprotein transcripts were hyperbolic, and reached well-defined plateaus with breakpoints in a narrow range of 0.08-0.19 μg Se/g. No selenoprotein transcript was altered by supernutritional Se. In summary, these results clearly indicate that the NRC dietary Se requirement should be raised to 0.4 μg Se/g, at least for poults, to meet the nutritional needs of the young turkey. The Se response curve plateaus further show that limits for turkey supplementation with selenite could safely be raised to 0.5 μg Se/g diet.
| S-EPMC5708738 | biostudies-literature
Project description:Brain Derived Neurotrophic Factor (BDNF) is a key molecule involved in plastic changes related to learning and memory. The expression of BDNF is highly regulated, and can lead to great variability in BDNF levels in healthy subjects. Changes in BDNF expression are associated with both normal and pathological aging and also psychiatric disease, in particular in structures important for memory processes such as the hippocampus and parahippocampal areas. Some interventions like exercise or antidepressant administration enhance the expression of BDNF in normal and pathological conditions. In this review, we will describe studies from rodents and humans to bring together research on how BDNF expression is regulated, how this expression changes in the pathological brain and also exciting work on how interventions known to enhance this neurotrophin could have clinical relevance. We propose that, although BDNF may not be a valid biomarker for neurodegenerative/neuropsychiatric diseases because of its disregulation common to many pathological conditions, it could be thought of as a marker that specifically relates to the occurrence and/or progression of the mnemonic symptoms that are common to many pathological conditions.
| S-EPMC6692714 | biostudies-literature
Project description:The goal of this study was to determine the effects of dietary selenium levels on translational control of selenoprotein synthesis in mouse liver.
2013-09-17 | GSE46038 | GEO
Project description:Selenium is transferred from the mouse dam to its neonate via milk. Milk contains selenium in selenoprotein form as selenoprotein P (Sepp1) and glutathione peroxidase-3 (Gpx3) as well as in non-specific protein form as selenomethionine. Selenium is also present in milk in uncharacterized small-molecule form. We eliminated selenomethionine from the mice in these experiments by feeding a diet that contained sodium selenite as the source of selenium. Selenium-replete dams with deletion of Sepp1 or Gpx3 were studied to assess the effects of these genes on selenium transfer to the neonate. Sepp1 knockout caused a drop in milk selenium to 27% of the value in wild-type milk and a drop in selenium acquisition by the neonates to 35%. In addition to decreasing milk selenium by eliminating Sepp1, deletion of Sepp1 causes a decline in whole-body selenium, which likely also contributes to the decreased transfer of selenium to the neonate. Deletion of Gpx3 did not decrease milk selenium content or neonate selenium acquisition by measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg selenium/kg diet), milk Sepp1 transfers a large amount of selenium to neonates but the transfer of selenium by Gpx3 is below detection by our methods.
| S-EPMC4113432 | biostudies-literature