Defective utilization of haem in selenium-deficient rat liver.
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ABSTRACT:
SUBMITTER: Correia MA
PROVIDER: S-EPMC1152209 | biostudies-other | 1983 Jul
REPOSITORIES: biostudies-other
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Project description:1. Hepatic microsomal cytochrome P-450 concentrations are lower in selenium-deficient rats treated with phenobarbital for 4 days than in similarly treated control rats. 2. No defect in haem synthesis was found on the basis of measurements of delta-aminolaevulinate synthase (EC 2.3.1.37), delta-aminolaevulinate dehydratase (EC 4.2.1.24) and ferrochelatase (EC 4.99.1.1) activities, and urinary excretion of delta-aminolaevulinate, porphobilinogen, uroporphyrin and coproporphyrin. 3. No defect in apo-(cytochrome P-450) separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 4. An increase in haem catabolism was found. An 8-fold increase in hepatic microsomal haem oxygenase (EC 1.14.99.3) activity occurred in selenium-deficient rats after phenobarbital treatment, compared with a less than 2-fold increase in control rats. Also excretion of 14CO in the breath after administration of delta-amino[5-14C]laevulinate was greater by phenobarbital-treated selenium-deficient rats than by similarly treated controls. 5. These studies demonstrate that the defective induction of cytochrome P-450 by phenobarbital in selenium-deficient rats is accompanied by increased haem catabolism. This could be due to increased breakdown of cytochrome P-450 or to catabolism of haem before it attaches to the apo-cytochrome. The role of selenium in stabilizing cytochrome P-450 and/or in protecting haem from breakdown remains to be determined.
| S-EPMC1184121 | biostudies-other
Project description:Selenium (Se)-deficient mice were labelled in vivo with single pulses of [75Se]selenite, and the intrahepatic distribution of the trace element was studied by subcellular fractionation. At 1 h after intraperitoneal injection of 3.3 or 10 micrograms of Se/kg body weight, 15% of the respective doses were found in the liver. Accumulation in the subcellular fractions followed the order: Golgi vesicular much greater than lysosomal greater than cytosolic = microsomal greater than mitochondrial, peroxisomal, nuclear and plasma-membrane fraction. At a dose of 3.3 micrograms/kg, more than 90% of the hepatic Se was protein-bound. When cross-contamination was accounted for, the following specific Se contents of the subcellular compartments were extrapolated: Golgi apparatus, 7.50 pmol/mg; cytosol, 0.90 pmol/mg; endoplasmic reticulum, 0.80 pmol/mg; mitochondria, 0.49 pmol/mg; nuclei, lysosomes, peroxisomes and plasma membrane, less than 0.4 pmol/mg. At 10 micrograms/kg, a roughly 2-3-fold increase in Se content of all fractions was found without major changes in the intrahepatic distribution pattern. An extraordinary rise in the cytosolic fraction was due to an apparently non-protein-bound Se pool. At 24 h after dosing, total hepatic Se had decreased to 6% of the initial dose and had become predominantly protein-bound. The 60% decrease in hepatic Se was reflected in a similar fall in the subcellular levels of the trace element. The Golgi apparatus still had the highest specific Se content, although accumulation was 5 times less than that after 1 h. The cytosolic pool accounted for 50% of the hepatic Se at both labelling times. After 1 h the Golgi apparatus was, with 19%, the second largest intrahepatic pool, followed by the endoplasmic reticulum with 16%. The high affinity and fast response of the Golgi apparatus to Se supplementation of deficient mice is interpreted in terms of a predominant function of this cell compartment in the processing and the export of Se-proteins from the liver.
| S-EPMC1138395 | biostudies-other
Project description:The diversity of selenoproteins raises the question of why so many life forms require selenium. Selenoproteins are found in bacteria, archaea, and many eukaryotes. In photosynthetic microorganisms, the essential requirement for selenium has been reported in 33 species belonging to six phyla, although its biochemical significance is still unclear. According to genome databases, 20 species are defined as selenoprotein-producing organisms, including five photosynthetic organisms. In a marine coccolithophorid, Emiliania huxleyi (Haptophyta), we recently found unique characteristics of selenium utilization and novel selenoproteins using (75)Se-tracer experiments. In E. huxleyi, selenite, not selenate, is the main substrate used and its uptake is driven by an ATP-dependent high-affinity, active transport system. Selenite is immediately metabolized to low-molecular mass compounds and partly converted to at least six selenoproteins, named EhSEP1-6. The most (EhSEP2) and second-most abundant selenoproteins (EhSEP1) are disulfide isomerase (PDI) homologous protein and thioredoxin reductase (TR) 1, respectively. Involvement of selenium in PDI is unique in this organism, while TR1 is also found in other organisms. In this review, we summarize physiological, biochemical, and molecular aspects of selenium utilization by microalgae and discuss their strategy of selenium utilization.
| S-EPMC6254913 | biostudies-literature
Project description:BackgroundThe essential trace element selenium is used in a wide variety of biological processes. Selenocysteine (Sec), the 21st amino acid, is co-translationally incorporated into a restricted set of proteins. It is encoded by an UGA codon with the help of tRNASec (SelC), Sec-specific elongation factor (SelB) and a cis-acting mRNA structure (SECIS element). In addition, Sec synthase (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of Sec on the tRNASec. Selenium is also found in the form of 2-selenouridine, a modified base present in the wobble position of certain tRNAs, whose synthesis is catalyzed by YbbB using selenophosphate as a precursor.ResultsWe analyzed completely sequenced genomes for occurrence of the selA, B, C, D and ybbB genes. We found that selB and selC are gene signatures for the Sec-decoding trait. However, selD is also present in organisms that do not utilize Sec, and shows association with either selA, B, C and/or ybbB. Thus, selD defines the overall selenium utilization. A global species map of Sec-decoding and 2-selenouridine synthesis traits is provided based on the presence/absence pattern of selenium-utilization genes. The phylogenies of these genes were inferred and compared to organismal phylogenies, which identified horizontal gene transfer (HGT) events involving both traits.ConclusionThese results provide evidence for the ancient origin of these traits, their independent maintenance, and a highly dynamic evolutionary process that can be explained as the result of speciation, differential gene loss and HGT. The latter demonstrated that the loss of these traits is not irreversible as previously thought.
| S-EPMC1273633 | biostudies-literature
Project description:Selenium (Se) has been proven to be an essential trace element for organism. Se deficiency in poultry can cause widespread damage, such as exudative diathesis. The liver is not only the main organ of metabolism, but also one of the organs with high Se content in organism. Recent studies have shown that solute carrier family 7 member 11 (SLC7A11) plays a key role in the negative regulation of ferroptosis. In order to explore the mechanism of Se deficiency induces liver ferroptosis in broilers, and the role of microRNAs (miRNAs) in this process, we divided broilers into 2 groups: control group (0.2 mg/kg Se) and Se deficiency group (0.03 mg/kg Se). Hematoxylin-Eosin staining detected liver tissue damage in broilers. Predicted and verified the targeting relationship between miR-129-3p and SLC7A11 through miRDB and dual luciferase report experiments. The genes related to ferroptosis were detected by qRT-PCR and Western Blot. The results showed that the expression level of miR-129-3p mRNA in Se-deficient liver was significantly increased. To understand whether the miR-129-3p/SLC7A11 axis could involve in the process of ferroptosis, our further research showed that overexpression of miR-129-3p could reduce the expression of SLC7A11 and its downstream GCL, GSS, and GPX4, thereby inducing ferroptosis. These data indicates that miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage. Graphical abstract Image, graphical abstract
| S-EPMC9700304 | biostudies-literature
Project description:In intensive care units, sepsis is the first cause of death. In this pathology, inflammation and oxidative status play a crucial role in patient outcomes. Interestingly, 92% of septic patients exhibit low selenium plasma concentrations (a component of antioxidant enzymes). Moreover, Spirulina platensis, a blue-green algae, demonstrated anti-inflammatory effects. In this context, the main purpose of our study was to analyze the effect of a selenium-enriched spirulina after a selenium deficiency on sepsis outcome in rats. Sixty-four rats were fed 12 weeks with a selenium-deficient food. After 8 weeks, rats were supplemented (via drinking water) for 4 weeks with sodium selenite (Se), spirulina (Spi), or selenium-enriched spirulina (SeSp). Sepsis was then induced by cecal ligature and puncture, and survival duration was observed. The plasma selenium concentration was measured by ICPMS. Expression of GPx1 and GPx3 mRNA was measured by RT-PCR. Blood parameters (lactates and HCO3 - concentrations, pH, PO2 , and PCO2 ) were analyzed at 0, 1, and 2 h as well as inflammatory cytokines (IL-6, TNF-α, IL-10). Sodium selenite and SeSP supplementations restored plasma selenium concentration prior to sepsis. The survival duration of SeSP septic rats was significantly lower than that of selenium-supplemented ones. Gpx1 mRNA was increased after a selenium-enriched spirulina supplementation while Gpx3 mRNA levels remained unchanged. Furthermore, sodium selenite prevented sepsis-induced acidosis. Our results show that on a basis of a Se deficiency, selenium-enriched spirulina supplementations significantly worsen sepsis outcome when compared to Se supplementation. Furthermore, Se supplementation but not selenium-enriched spirulina supplementation decreased inflammation and restored acid-base equilibrium after a sepsis induction.
| S-EPMC8290477 | biostudies-literature
Project description:The effects of selenium nanoparticles (SeNPs) on the antioxidant capacity in Sprague-Dawley (SD) rats were investigated. The rats were given intragastric administration of an SeNP suspension at doses of 0, 2, 4, and 8 mg Se/kg BW for two weeks. The antioxidant capacity in serum and organic tissues (liver, heart, and kidney) and the gene expression levels of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 4 (GPX4) in the liver were measured. Buffalo rat liver (BRL) cell lines were further constructed to explore the cytotoxicity mechanism induced by SeNPs through the determination of antioxidant capacity; cell activity; apoptosis; and Caspase-3, Caspase-8, and Caspase-9 family activities. The results showed that SeNP administration over 4.0 mg Se/kg BW decreased the antioxidant capacities in the serum, liver, and heart and downregulated mRNA expression of GPX1 and GPX4 in the liver. The BRL cell line experiments showed that treatment with over 24 μM SeNPs decreased the viability of the cells and damaged the antioxidant capacity. Flow cytometry analysis showed that decreased cell viability induced by SeNPs is mainly due to apoptosis, rather than cell necrosis. Caspase-3 and Caspase-8 activities were also increased when BRL cells were treated with 24 μM and 48 μM SeNPs. Taken together, a nonlethal level of SeNPs could impair the antioxidant capacity in serum and organic tissues of rats, and the liver is the most sensitive to the toxicity of SeNPs. A pharmacological dose of SeNPs could lead to cytotoxicity and induce cell death through apoptosis and extrinsic pathways contributing to SeNP-induced apoptosis in BRL cells.
| S-EPMC7453254 | biostudies-literature
Project description:The role of vitamin E and selenium as protective agents against oxidative stress was evaluated by measuring liver chemiluminescence in situ. Weanling rats fed a vitamin E- and selenium-deficient diet showed liver chemiluminescence that was increased 60 and 100% over control values at 16 and 18 days respectively after weaning. At day 21, the double deficiency led to hepatic necrosis, as observed by optical and electron microscopy, and increased serum levels of lactate dehydrogenase and alanine aminotransferase. Single deficiencies, in either vitamin E or selenium, did not produce liver necrosis but increased liver chemiluminescence. Vitamin E deficiency led to a 23 and 50% increase in liver emission at days 18 and 20 respectively; selenium deficiency produced a 64% increase at day 16. The activity of liver selenium-glutathione peroxidase diminished to 13% of the control value in the rats fed doubly deficient and selenium-deficient diets. Activities of superoxide dismutase, catalase and non-selenium-glutathione peroxidase were not modified by the different diets. These results suggest that oxy-radical generation may play a major role in hepatic necrosis in vitamin E- and selenium-deficiency.
| S-EPMC1147716 | biostudies-other
Project description:BackgroundSelenium (Se) is a trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine (SeU). Selenophosphate synthetase (SelD) is required for both utilization traits. However, previous research also revealed SelDs in two organisms lacking Sec and SeU, suggesting a possible additional use of Se that is dependent on SelD.ResultsIn this study, we conducted comparative genomics and phylogenetic analyses to characterize genes involved in Se utilization. Candidate genes identified included SelA/SelB and YbbB that define Sec and SeU pathways, respectively, and NADH oxidoreductase that is predicted to generate a SelD substrate. In addition, among 227 organisms containing SelD, 10 prokaryotes were identified that lacked SelA/SelB and YbbB. Investigation of selD neighboring genes in these organisms revealed a SirA-like protein and two hypothetical proteins HP1 and HP2 that were strongly linked to a novel Se utilization. With these new signature proteins, 32 bacteria and archaea were found that utilized these proteins, likely as part of the new Se utilization trait. Metabolic labeling of one organism containing an orphan SelD, Enterococcus faecalis, with 75Se revealed a protein containing labile Se species that could be released by treatment with reducing agents, suggesting non-Sec utilization of Se in this organism.ConclusionThese studies suggest the occurrence of a third Se utilization trait in bacteria and archaea.
| S-EPMC2432076 | biostudies-literature
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