The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Vasilaki, Aikaterini T; Talwar, Dinesh; Duncan, Andrew

2016-04-01

The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower zinc and selenium. They may also be influenced by their binding proteins, such as albumin. The aim of the present study was to examine the relationships between plasma zinc, selenium and the systemic inflammatory response in a large cohort of patients referred for nutritional screen and also to examine these relationships in patients with critical illness. Patients referred for nutritional assessment of zinc (n = 743) and selenium (n = 833) and 114 patients with critical illness were examined. Intra-assay imprecision was <10% for these analytes. In the nutritional screen cohort, plasma zinc was significantly associated with CRP (rs = -0.404, p < 0.001) and albumin (rs = 0.588, p < 0.001). For each CRP category (≤10, 11-80, >80 mg/l) the zinc/albumin ratio x100 was similar (31, 33 and 32 respectively, p = 0.029). Plasma selenium was significantly associated with CRP (rs = -0.489, p < 0.001) and albumin (rs = 0.600, p < 0.001). With increasing CRP category (≤10, 11-80, >80 mg/l) the selenium/albumin ratio ×100 was lower (2.3, 2.1 and 1.8 respectively, p < 0.001). Similar relationships were also observed in the cohort of patients with critical illness. Plasma zinc was associated with both CRP and albumin. The impact of the systemic inflammatory response could be largely adjusted by albumin concentrations. Plasma selenium was associated with both CRP and albumin. The impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Selenium levels in human breast carcinoma tissue are associated with a common polymorphism in the gene for SELENOP (Selenoprotein P).

PubMed

Ekoue, Dede N; Zaichick, Sofia; Valyi-Nagy, Klara; Picklo, Matthew; Lacher, Craig; Hoskins, Kent; Warso, Michael A; Bonini, Marcelo G; Diamond, Alan M

2017-01-01

Selenium supplementation of the diets of rodents has consistently been shown to suppress mammary carcinogenesis and some, albeit not all, human epidemiological studies have indicated an inverse association between selenium and breast cancer risk. In order to better understand the role selenium plays in breast cancer, 30 samples of tumor tissue were obtained from women with breast cancer and analyzed for selenium concentration, the levels of several selenium-containing proteins and the levels of the MnSOD anti-oxidant protein. Polymorphisms within the genes for these same proteins were determined from DNA isolated from the tissue samples. There was a wide range of selenium in these tissues, ranging from 24 to 854ng/gm. The selenium levels in the tissues were correlated to the genotype of the SELENOP selenium carrier protein, but not to other proteins whose levels have been reported to be responsive to selenium availability, including GPX1, SELENOF and SBP1. There was an association between a polymorphism in the gene for MnSOD and the levels of the encoded protein. These studies were the first to examine the relationship between selenium levels, genotypes and protein levels in human tissues. Furthermore, the obtained data provide evidence for the need to obtain data about the effects of selenium in breast cancer by examining samples from that particular tissue type. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer

PubMed Central

Ansong, Emmanuel; Ying, Qi; Ekoue, Dede N.; Deaton, Ryan; Hall, Andrew R.; Kajdacsy-Balla, Andre; Yang, Wancai; Gann, Peter H.; Diamond, Alan M.

2015-01-01

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease. PMID:25993660

Mitochondrial Protein Profile in Mice with Low or Excessive Selenium Diets

PubMed Central

Hu, Lianmei; Wang, Congcong; Zhang, Qin; Yan, Hao; Li, Ying; Pan, Jiaqiang; Tang, Zhaoxin

2016-01-01

Dietary selenium putatively prevents oxidative damage, whereas excessive selenium may lead to animal disorder. In this study, we investigated the effects of low and excessive levels of dietary selenium on oxidative stress and mitochondrial proteins in mouse liver. Six to eight week old mice were fed a diet with low, excessive, or moderate (control) levels of selenium (sodium selenite). The selenium concentration and oxidative stress-related parameters in hepatic mitochondria were evaluated. Two-dimensional electrophoresis and mass spectrometry were applied to identify the differentially-expressed proteins associated with dietary selenium. The selenium content of the livers in mice with the low selenium diet was significantly lower than that of the control, while that of mice fed excessive levels was significantly higher. In both groups oxidative stress in hepatic mitochondria was found; accompanied by lower superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels and higher malondialdehyde (MDA) content, compared with the control group. Furthermore, ten proteins in the hepatic mitochondria of the selenium-low or -excessive groups with more than two-fold differences in abundance compared with the control group were identified. The differentially-expressed proteins in hepatic mitochondria may be associated with dietary (low or excessive) selenium-induced oxidative stress. PMID:27428959

Bioaccumulation and distribution of selenium in Enterococcus durans.

PubMed

Pieniz, Simone; Andreazza, Robson; Mann, Michele Bertoni; Camargo, Flávio; Brandelli, Adriano

2017-03-01

Selenium is an essential nutrient for all living organisms. Under appropriate conditions lactic acid bacteria (LAB) are capable for accumulating large amounts of trace elements, such as selenium, and incorporating them into organic compounds. In this study, the capacity of selenium bioaccumulation by Enterococcus durans LAB18s was evaluated. The distribution of organic selenium in selenium-enriched E. durans LAB18s biomass was analyzed, and the highest percentage of organic selenium was found in the fraction of total protein, followed by the fractions of polysaccharides and nucleic acids. When the protein fraction was obtained by different extractions (water, NaCl, ethanol and NaOH) it was demonstrated that alkali-soluble protein showed the higher Selenium content. Analysis of protein fractions by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that selenium was present in the proteins ranging from 23 to 100kDa. The cells were analyzed by scanning electron microscopy (SEM); scanning electron microscopy/energy dispersive spectrometry (SEM/EDS) and transmission electron microscopy (TEM). SEM, TEM and SEM/EDS showed the morphology, the selenium particles bioaccumulated into and on the cells and the amounts of selenium present into the cells, respectively. Thus, the isolate E. durans LAB18s can be a promising probiotic to be used as selenium-enriched biomass in feed trials. Copyright © 2016 Elsevier GmbH. All rights reserved.

Sulfur and selenium antioxidants: challenging radical scavenging mechanisms and developing structure-activity relationships based on metal binding.

PubMed

Zimmerman, Matthew T; Bayse, Craig A; Ramoutar, Ria R; Brumaghim, Julia L

2015-04-01

Because sulfur and selenium antioxidants can prevent oxidative damage, numerous animal and clinical trials have investigated the ability of these compounds to prevent the oxidative stress that is an underlying cause of cardiovascular disease, Alzheimer's disease, and cancer, among others. One of the most common sources of oxidative damage is metal-generated hydroxyl radical; however, very little research has focused on determining the metal-binding abilities and structural attributes that affect oxidative damage prevention by sulfur and selenium compounds. In this review, we describe our ongoing investigations into sulfur and selenium antioxidant prevention of iron- and copper-mediated oxidative DNA damage. We determined that many sulfur and selenium compounds inhibit Cu(I)-mediated DNA damage and that DNA damage prevention varies dramatically when Fe(II) is used in place of Cu(I) to generate hydroxyl radical. Oxidation potentials of the sulfur or selenium compounds do not correlate with their ability to prevent DNA damage, highlighting the importance of metal coordination rather than reactive oxygen species scavenging as an antioxidant mechanism. Additional gel electrophoresis, mass spectrometry, and UV-visible studies confirmed sulfur and selenium antioxidant binding to Cu(I) and Fe(II). Ultimately, our studies established that both the hydroxyl-radical-generating metal ion and the chemical environment of the sulfur or selenium significantly affect DNA damage prevention and that metal coordination is an essential mechanism for these antioxidants. Copyright © 2015 Elsevier Inc. All rights reserved.

Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.

PubMed

Lee, Eui Kyung; Shin, Young-Jun; Park, Eun Young; Kim, Nam Deuk; Moon, Aree; Kwack, Seung Jun; Son, Ji Yeon; Kacew, Sam; Lee, Byung Mu; Bae, Ok-Nam; Kim, Hyung Sik

2017-04-01

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl 2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl 2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl 2 -treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and β-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl 2 -exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl 2 , CdCl 2 , or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.

[The selenium haemostasis during experimental anaphylaxis reaction in rats treated with reduced glutathione and selenium enriched spirulina].

PubMed

Golubkina, N A; Mazo, V K; Gmoshinskiĭ, I V; Zorin, S N; Tambiev, A Kh; Kirikova, N N

2000-01-01

The main events caused by anaphilaxis in selenium haemostasis in rats include significant increase of selenium excretion with urine (6.36 +/- 1.18 nM Se/18 h., n = 10, compared with 1.72 +/- 0.38 nM Se/18 h., n = 10) and decrease of selenium plasma/selenium erythrocytes ratio from 0.939 to 0.791. Reduced glutathione (G-SH) administration led to 1.5-fold decrease of plasma selenium level and 1.3-fold increase of selenium concentration in intestinal walls of sensitized rats (r = -0.720, P < 0.001). Chromatographic separation of plasma proteins showed that intragastric intubation of G-SH to sensibilized rats significantly decreased the protein P content and did not influence the concentration of Se-GSHPx, thus indicating the local selenium acceptor role of G-SH. G-SH administration did not influence the intestinal permeability in sensitised rats while use of complex additive: G-SH and selenium enriched spirulina--normalized the latter parameter and the ratio of protein P/Se-GSHPx in plasma.

Se metallomics during lactic fermentation of Se-enriched yogurt.

PubMed

Palomo, María; Gutiérrez, Ana M; Pérez-Conde, M Concepción; Cámara, Carmen; Madrid, Yolanda

2014-12-01

Selenium biotransformation by lactic acid bacteria during the preparation of Se-enriched yogurt was evaluated. The study focused on the distribution of selenium in the aqueous soluble protein fraction and the detection of selenoamino acids. Screening of selenium in Tris-buffer-urea soluble fraction was carried out by sodium dodecyl sulphate polyacrylamide gel electrophoresis after pre-fractionating with asymmetric field flow fractionation using inductively coupled plasma-mass spectrometry as the detector. Selenium-containing fractions were identified by peptide mapping using nano LC-ESI/LTQMS. Proteins such as thioredoxin, glutaredoxin, albumin, β-lactoglobulin, and lactoperoxidase were identified in the selenium-containing fraction. All these proteins were detected in both the control and the selenium-enriched yogurt except chaperones, which were only detected in the control samples. Chaperones are heat-shock proteins expressed in response to elevated temperature or other cellular stresses. Selenium may have an effect on chaperones expression in Lactobacillus. For the amino acids analysis, selenocysteine was the primary seleno-containing species. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

NASA Astrophysics Data System (ADS)

Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

2012-07-01

The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

Characterization of the UGA-recoding and SECIS-binding activities of SECIS-binding protein 2.

PubMed

Bubenik, Jodi L; Miniard, Angela C; Driscoll, Donna M

2014-01-01

Selenium, a micronutrient, is primarily incorporated into human physiology as selenocysteine (Sec). The 25 Sec-containing proteins in humans are known as selenoproteins. Their synthesis depends on the translational recoding of the UGA stop codon to allow Sec insertion. This requires a stem-loop structure in the 3' untranslated region of eukaryotic mRNAs known as the Selenocysteine Insertion Sequence (SECIS). The SECIS is recognized by SECIS-binding protein 2 (SBP2) and this RNA:protein interaction is essential for UGA recoding to occur. Genetic mutations cause SBP2 deficiency in humans, resulting in a broad set of symptoms due to differential effects on individual selenoproteins. Progress on understanding the different phenotypes requires developing robust tools to investigate SBP2 structure and function. In this study we demonstrate that SBP2 protein produced by in vitro translation discriminates among SECIS elements in a competitive UGA recoding assay and has a much higher specific activity than bacterially expressed protein. We also show that a purified recombinant protein encompassing amino acids 517-777 of SBP2 binds to SECIS elements with high affinity and selectivity. The affinity of the SBP2:SECIS interaction correlated with the ability of a SECIS to compete for UGA recoding activity in vitro. The identification of a 250 amino acid sequence that mediates specific, selective SECIS-binding will facilitate future structural studies of the SBP2:SECIS complex. Finally, we identify an evolutionarily conserved core cysteine signature in SBP2 sequences from the vertebrate lineage. Mutation of multiple, but not single, cysteines impaired SECIS-binding but did not affect protein localization in cells.

Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor.

PubMed

Spatzal, Thomas; Perez, Kathryn A; Howard, James B; Rees, Douglas C

2015-12-16

Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo-cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 Å resolution structure reveals selenium occupying the S2B site of FeMo-cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse-chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 Å, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis.

Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subedi, Amit; Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570; Shimizu, Takeshi

2016-06-03

Peptidyl prolyl cis/trans isomerization by Pin1 regulates various oncogenic signals during cancer progression, and its inhibition through multiple approaches has established Pin1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent Pin1 inhibitors. We utilized phosphorylation-dependent binding of Pin1 to its specific substrate to develop a screening system for Pin1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as Pin1 inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent Pin1 inhibitors that inhibited cancer cell proliferation. -- Highlights: •Novel screening for Pin1 inhibitors basedmore » on Pin1 binding is developed. •A novel selenium compound is discovered as Pin1 inhibitor. •Activity guided chemical synthesis of selenium derivatives resulted potent Pin1 inhibitors.« less

Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

PubMed

Chen, Menghao; Li, Xiaojing; Fan, Ruifeng; Cao, Changyu; Yao, Haidong; Xu, Shiwen

2017-11-01

The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl 2 , 150mg/kg) and sodium selenite (Na 2 SeO 3 , 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

PubMed

Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

2017-06-01

The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

Spectrophotometric evaluation of selenium binding by Saccharomyces cerevisiae ATCC MYA-2200 and Candida utilis ATCC 9950 yeast.

PubMed

Kieliszek, Marek; Błażejak, Stanisław; Płaczek, Maciej

2016-05-01

In this study, the ability of selenium binding the biomas of Saccharomyces cerevisiae ATCC MYA-2200 and Candida utilis ATCC 9950 was investigated. Sodium selenite(IV) salts were added to the experimental media at concentrations of 10, 20, 40, and 60 mg Se(4+) L(-1). In the tested concentration range, one concentration reported a significant reduction in the biomass yield of both yeast strains. Intense growth was observed for C. utilis yeast, which reached the highest biomass yield of 15 gd.w.L(-1) after 24h cultivation in the presence of 10mg Se(4+) L(-1). Based on the use of spectrophotometric method for the determination of selenium content by using Variamine Blue as a chromogenic agent, efficient accumulation of this element in the biomass of the investigated yeast was observed. The highest amount of selenium, that is, 5.64 mg Se(4+)gd.w.(-1), was bound from the environment by S. cerevisiae ATCC MYA-2200 cultured in the presence of 60 mg Se(4+) L(-1) medium 72h Slightly less amount, 5.47 mg Se(4+) gd.w.(-1), was absorbed by C. utilis ATCC 9950 during similar cultural conditions. Based on the results of the biomass yield and the use of selenium from the medium, it can be observed that yeasts of the genus Candida are more efficient in binding this element, and this property finds practical application in the production of selenium-enriched yeast. Copyright © 2016 Elsevier GmbH. All rights reserved.

The intensity of tyrosine nitration is associated with selenite and selenate toxicity in Brassica juncea L.

PubMed

Molnár, Árpád; Feigl, Gábor; Trifán, Vanda; Ördög, Attila; Szőllősi, Réka; Erdei, László; Kolbert, Zsuzsanna

2018-01-01

Selenium phytotoxicity involves processes like reactive nitrogen species overproduction and nitrosative protein modifications. This study evaluates the toxicity of two selenium forms (selenite and selenate at 0µM, 20µM, 50µM and 100µM concentrations) and its correlation with protein tyrosine nitration in the organs of hydroponically grown Indian mustard (Brassica juncea L.). Selenate treatment resulted in large selenium accumulation in both Brassica organs, while selenite showed slight root-to-shoot translocation resulting in a much lower selenium accumulation in the shoot. Shoot and root growth inhibition and cell viability loss revealed that Brassica tolerates selenate better than selenite. Results also show that relative high amounts of selenium are able to accumulate in Brassica leaves without obvious visible symptoms such as chlorosis or necrosis. The more severe phytotoxicity of selenite was accompanied by more intense protein tyrosine nitration as well as alterations in nitration pattern suggesting a correlation between the degree of Se forms-induced toxicities and nitroproteome size, composition in Brassica organs. These results imply the possibility of considering protein tyrosine nitration as novel biomarker of selenium phytotoxicity, which could help the evaluation of asymptomatic selenium stress of plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of Selenium Content in the Culture Medium on Protein Profile of Yeast Cells Candida utilis ATCC 9950

PubMed Central

Kieliszek, Marek; Błażejak, Stanisław; Bzducha-Wróbel, Anna

2015-01-01

Selenium is an essential trace element for human health and it has been recognized as a component of several selenoproteins with crucial biological functions. It has been identified as a component of active centers of many enzymes, as well as integral part of biologically active complexes. The aim of the study was to evaluate the protein content and amino acid profile of the protein of fodder yeast Candida utilis ATCC 9950 cultured in media control and experimental enriched selenium. Protein analysis was performed using SDS-PAGE method consisting of polyacrylamide gel electrophoresis in the presence of SDS. The highest contents of soluble protein (49,5 mg/g) were found in yeast cells after 24-hour culture conducted in control (YPD) medium. In the presence of selenium there were determined small amounts of protein content. With increasing time of yeast culture (to 72 hours) the control and experimental media were reported to reduce soluble protein content. In electropherogram proteins from control cultures was observed the presence of 10 protein fractions, but in all the experimental cultures (containing 20, 30, and 40 mg/L selenium) of 14 protein fractions. On the basis of the molecular weights of proteins, it can be concluded that they were among others: selenoprotein 15 kDa and selenoprotein 18 kDa. PMID:26185592

Alcohol, gestation and breastfeeding: selenium as an antioxidant therapy.

PubMed

Ojeda, Ma Luisa; Nogales, Fatima; Vázquez, Beatriz; Delgado, Ma José; Murillo, Ma Luisa; Carreras, Olimpia

2009-01-01

The aim of this paper is to study the relationship between alcohol, selenium and oxidative stress in breastfeeding rat pups exposed to ethanol during gestation and lactation. We have also studied how a Se-supplemented diet among mothers could prevent different oxidative liver disorders in the pups. Pups of 21 days were randomized into four groups: control group (C), alcohol group (A), alcohol selenium group (AS) and control selenium group (CS). Alcohol was supplied to their mothers for 13 weeks (induction, reproduction, gestation and lactation periods). The selenium-supplemented diet contained 0.5 ppm as selenite. We determined serum and liver selenium by graphite-furnace atomic absorption spectrometry. We measured antioxidant enzyme activities: glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD); and lipid peroxidation (TBARS) and protein carbonyl (PC) by a spectrophotometric method in the liver. In the liver of pups, exposure to ethanol provoked a decrease in selenium and GPx activity and an increase in GR and CAT activity, as well as in carbonyl groups in protein. A pups had higher Se levels and GPx activity in serum than C pups. Administering Se with alcohol balances the activities of scavenging enzymes and reduces peroxidation protein products. These results suggest that selenium could be effective in neutralizing the damage of ethanol consumption during gestation and lactation in pups since it repairs selenium levels in liver as well as the activity of scavenging enzymes and peroxidation protein products. In serum, Se also recovers GPx activity and increases the levels of Se that are available to other organs.

A tale of two toxicities: malformed selenoproteins and oxidative stress both contribute to selenium stress in plants

PubMed Central

Van Hoewyk, Doug

2013-01-01

Background Despite selenium's toxicity in plants at higher levels, crops supply most of the essential dietary selenium in humans. In plants, inorganic selenium can be assimilated into selenocysteine, which can replace cysteine in proteins. Selenium toxicity in plants has been attributed to the formation of non-specific selenoproteins. However, this paradigm can be challenged now that there is increasingly abundant evidence suggesting that selenium-induced oxidative stress also contributes to toxicity in plants. Scope This Botanical Briefing summarizes the evidence indicating that selenium toxicity in plants is attributable to both the accumulation of non-specific selenoproteins and selenium-induced oxidative stress. Evidence is also presented to substantiate the claim that inadvertent selenocysteine replacement probably impairs or misfolds proteins, which supports the malformed selenoprotein hypothesis. The possible physiological ramifications of selenoproteins and selenium-induced oxidative stress are discussed. Conclusions Malformed selenoproteins and oxidative stress are two distinct types of stress that drive selenium toxicity in plants and could impact cellular processes in plants that have yet to be thoroughly explored. Although challenging, deciphering whether the extent of selenium toxicity in plants is imparted by selenoproteins or oxidative stress could be helpful in the development of crops with fortified levels of selenium. PMID:23904445

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs123

PubMed Central

Barcus, Matthew; Kim, Jonggun; Lum, Krystal L; Mills, Courtney; Lei, Xin Gen

2016-01-01

Background: Prolonged high intakes of dietary selenium have been shown to induce gestational diabetes in rats and hyperinsulinemia in pigs. Objective: Two experiments were conducted to explore metabolic and molecular mechanisms for the diabetogenic potential of high dietary selenium intakes in pigs. Methods: In Expt. 1, 16 Yorkshire-Landrace-Hampshire crossbred pigs (3 wk old, body weight = 7.5 ± 0.81 kg, 50% males and 50% females) were fed a corn-soybean meal basal diet supplemented with 0.3 or 1.0 mg Se/kg (as selenium-enriched yeast for 6 wk). In Expt. 2, 12 pigs of the same crossbreed (6 wk old, body weight = 16.0 ± 1.8 kg) were fed a similar basal diet supplemented with 0.3 or 3.0 mg Se/kg for 11 wk. Biochemical and gene and protein expression profiles of lipid and protein metabolism and selenoproteins in plasma, liver, muscle, and adipose tissues were analyzed. Results: In Expt. 1, the 1-mg-Se/kg diet did not affect body weight or plasma concentrations of glucose and nonesterified fatty acids. In Expt. 2, the 3-mg-Se/kg diet, compared with the 0.3-mg-Se/kg diet, increased (P < 0.05) concentrations of plasma insulin (0.2 compared with 0.4 ng/mL), liver and adipose lipids (41% to 2.4-fold), and liver and muscle protein (10–14%). In liver, the 3-mg-Se/kg diet upregulated (P < 0.05) the expression, activity, or both of key factors related to gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK); 13%], lipogenesis [sterol regulatory element binding protein 1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FASN); 46–90%], protein synthesis [insulin receptor (INSR), P70 ribosomal protein S6 kinase (P70), and phosphorylated ribosomal protein S6 (P-S6); 88–105%], energy metabolism [AMP-activated protein kinase (AMPK); up to 2.8-fold], and selenoprotein glutathione peroxidase 3 (GPX3; 1.4-fold) and suppressed (P < 0.05) mRNA levels of lipolysis gene cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1; 88%) and selenoprotein gene selenoprotein W1 (SEPW1; 46%). In muscle, the 3-mg-Se/kg diet exerted no effect on the lipid profiles but enhanced (P < 0.05) expression of P-S6 and mammalian target of rapamycin (mTOR; 42–176%; protein synthesis); selenoprotein P (SELP; 40-fold); and tumor suppressor protein 53 (P53) and peroxisome proliferator–activated receptor γ (PPARG; 52–58%; lipogenesis) and suppressed (P < 0.05) expression of INSR (59%; insulin signaling); selenoprotein S (SELS); deiodinases, iodothyronine, type I (DIO1); and thioredoxin reductase 1 (TXNRD1; 50%; selenoproteins); and ACC1 and FASN (35–51%; lipogenesis). Conclusion: Our research showed novel roles, to our best knowledge, and mechanisms of high selenium intakes in regulating the metabolism of protein, along with that of lipid, in a tissue-specific fashion in pigs. PMID:27466604

High Dietary Selenium Intake Alters Lipid Metabolism and Protein Synthesis in Liver and Muscle of Pigs.

PubMed

Zhao, Zeping; Barcus, Matthew; Kim, Jonggun; Lum, Krystal L; Mills, Courtney; Lei, Xin Gen

2016-09-01

Prolonged high intakes of dietary selenium have been shown to induce gestational diabetes in rats and hyperinsulinemia in pigs. Two experiments were conducted to explore metabolic and molecular mechanisms for the diabetogenic potential of high dietary selenium intakes in pigs. In Expt. 1, 16 Yorkshire-Landrace-Hampshire crossbred pigs (3 wk old, body weight = 7.5 ± 0.81 kg, 50% males and 50% females) were fed a corn-soybean meal basal diet supplemented with 0.3 or 1.0 mg Se/kg (as selenium-enriched yeast for 6 wk). In Expt. 2, 12 pigs of the same crossbreed (6 wk old, body weight = 16.0 ± 1.8 kg) were fed a similar basal diet supplemented with 0.3 or 3.0 mg Se/kg for 11 wk. Biochemical and gene and protein expression profiles of lipid and protein metabolism and selenoproteins in plasma, liver, muscle, and adipose tissues were analyzed. In Expt. 1, the 1-mg-Se/kg diet did not affect body weight or plasma concentrations of glucose and nonesterified fatty acids. In Expt. 2, the 3-mg-Se/kg diet, compared with the 0.3-mg-Se/kg diet, increased (P < 0.05) concentrations of plasma insulin (0.2 compared with 0.4 ng/mL), liver and adipose lipids (41% to 2.4-fold), and liver and muscle protein (10-14%). In liver, the 3-mg-Se/kg diet upregulated (P < 0.05) the expression, activity, or both of key factors related to gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK); 13%], lipogenesis [sterol regulatory element binding protein 1 (SREBP1), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FASN); 46-90%], protein synthesis [insulin receptor (INSR), P70 ribosomal protein S6 kinase (P70), and phosphorylated ribosomal protein S6 (P-S6); 88-105%], energy metabolism [AMP-activated protein kinase (AMPK); up to 2.8-fold], and selenoprotein glutathione peroxidase 3 (GPX3; 1.4-fold) and suppressed (P < 0.05) mRNA levels of lipolysis gene cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1; 88%) and selenoprotein gene selenoprotein W1 (SEPW1; 46%). In muscle, the 3-mg-Se/kg diet exerted no effect on the lipid profiles but enhanced (P < 0.05) expression of P-S6 and mammalian target of rapamycin (mTOR; 42-176%; protein synthesis); selenoprotein P (SELP; 40-fold); and tumor suppressor protein 53 (P53) and peroxisome proliferator-activated receptor γ (PPARG; 52-58%; lipogenesis) and suppressed (P < 0.05) expression of INSR (59%; insulin signaling); selenoprotein S (SELS); deiodinases, iodothyronine, type I (DIO1); and thioredoxin reductase 1 (TXNRD1; 50%; selenoproteins); and ACC1 and FASN (35-51%; lipogenesis). Our research showed novel roles, to our best knowledge, and mechanisms of high selenium intakes in regulating the metabolism of protein, along with that of lipid, in a tissue-specific fashion in pigs. © 2016 American Society for Nutrition.

Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver.

PubMed

Gulyas, G; Csosz, E; Prokisch, J; Javor, A; Mezes, M; Erdelyi, M; Balogh, K; Janaky, T; Szabo, Z; Simon, A; Czegledi, L

2017-06-01

The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Proteomic study of differential protein expression in mouse lung tissues after aerosolized ricin poisoning.

PubMed

Guo, Zhendong; Han, Chao; Du, Jiajun; Zhao, Siyan; Fu, Yingying; Zheng, Guanyu; Sun, Yucheng; Zhang, Yi; Liu, Wensen; Wan, Jiayu; Qian, Jun; Liu, Linna

2014-04-28

Ricin is one of the most poisonous natural toxins from plants and is classified as a Class B biological threat pathogen by the Centers for Disease Control and Prevention (CDC) of U.S.A. Ricin exposure can occur through oral or aerosol routes. Ricin poisoning has a rapid onset and a short incubation period. There is no effective treatment for ricin poisoning. In this study, an aerosolized ricin-exposed mouse model was developed and the pathology was investigated. The protein expression profile in the ricin-poisoned mouse lung tissue was analyzed using proteomic techniques to determine the proteins that were closely related to the toxicity of ricin. 2D gel electrophoresis, mass spectrometry and subsequent biological functional analysis revealed that six proteins including Apoa1 apolipoprotein, Ywhaz 14-3-3 protein, Prdx6 Uncharacterized Protein, Selenium-binding protein 1, HMGB1, and DPYL-2, were highly related to ricin poisoning.

Selenium and Human Health: Witnessing a Copernican Revolution?

PubMed

Jablonska, Ewa; Vinceti, Marco

2015-01-01

In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets.

PubMed

Bermingham, Emma N; Bassett, Shalome A; Young, Wayne; Roy, Nicole C; McNabb, Warren C; Cooney, Janine M; Brewster, Di T; Laing, William A; Barnett, Matthew P G

2013-03-05

Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health.

Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets

PubMed Central

2013-01-01

Background Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. Methods Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. Results Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. Conclusions Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health. PMID:23497688

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury.

PubMed

Kim, Kyeong Seok; Yang, Hun Yong; Song, Hosup; Kang, Ye Rim; Kwon, JiHoon; An, JiHye; Son, Ji Yeon; Kwack, Seung Jun; Kim, Young-Mi; Bae, Ok-Nam; Ahn, Mee-Young; Lee, Jaewon; Yoon, Sungpil; Lee, Byung Mu; Kim, Hyung Sik

2017-01-01

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.

[Selenium treatment in thyreopathies].

PubMed

Sotak, Štefan

Selenium (latin Selenium) is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet and geographic area. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. The literature suggests that selenium supplementation of patients with Hashimotos thyroiditis is associated with a reduction in antithyroperoxidase antibody levels. Selenium supplementation also in mild Graves orbitopathy is associated with delayed progression of ocular disorders. As a consequence of this observation The European Group on Graves Orbitopathy recommend six months selenium preparates supportive therapy for patients with mild form of Graves orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis - selenium - supplementation.

Exploring the structural basis for selenium/mercury antagonism in Allium fistulosum

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNear, Jr., David H.; Afton, Scott E.; Caruso, Joseph A.

While continuing efforts are devoted to studying the mutually protective effect of mercury and selenium in mammals, few studies have investigated the mercury-selenium antagonism in plants. In this study, we report the metabolic fate of mercury and selenium in Allium fistulosum (green onion) after supplementation with sodium selenite and mercuric chloride. Analysis of homogenized root extracts via capillary reversed phase chromatography coupled with inductively coupled plasma mass spectrometry (capRPLC-ICP-MS) suggests the formation of a mercury-selenium containing compound. Micro-focused synchrotron X-ray fluorescence mapping of freshly excised roots show Hg sequestered on the root surface and outlining individual root cells, while Semore » is more evenly distributed throughout the root. There are also discrete Hg-only, Se-only regions and an overall strong correlation between Hg and Se throughout the root. Analysis of the X-ray absorption near edge structure (XANES) spectra show a 'background' of methylselenocysteine within the root with discrete spots of SeO{sub 3}{sup 2-}, Se{sup 0} and solid HgSe on the root surface. Mercury outlining individual root cells is possibly binding to sulfhydryl groups or plasma membrane or cell wall proteins, and in some places reacting with reduced selenium in the rhizosphere to form a mercury(II) selenide species. Together with the formation of the root-bound mercury(II) selenide species, we also report on the formation of cinnabar (HgS) and Hg{sup 0} in the rhizosphere. The results presented herein shed light on the intricate chemical and biological processes occurring within the rhizosphere that influence Hg and Se bioavailability and will be instrumental in predicting the fate and assisting in the remediation of these metals in the environment and informing whether or not fruit and vegetable food selection from aerial plant compartments or roots from plants grown in Hg contaminated soils, are safe for consumption.« less

Extremophilic Enzymatic Response: Role of Proteins in Controlling Selenium Nanoparticle Synthesis

DTIC Science & Technology

2014-11-28

Thermophiles ; Regensburg, Germany. September 2013. 2.- “Identification of one enzyme Involved in selenium nanoparticles Biosynthesis in Geobacillus...Objective To study the role of at least one protein ( enzyme ) from E1 (GWE1) on the synthesis of nano-Se particles. Note: This project...To identify protein(s) or enzyme (s) involved in nanoparticles formation. To identify the proteins or enzyme (s) involved in nanoparticles formation

Mitochondria-Mediated Protein Regulation Mechanism of Polymorphs-Dependent Inhibition of Nanoselenium on Cancer Cells

NASA Astrophysics Data System (ADS)

Wang, Ge; Guo, Yuming; Yang, Gai; Yang, Lin; Ma, Xiaoming; Wang, Kui; Zhu, Lin; Sun, Jiaojiao; Wang, Xiaobing; Zhang, Hua

2016-08-01

The present study was (i) to prepare two types of selenium nanoparticles, namely an amorphous form of selenium quantum dots (A-SeQDs) and a crystalline form of selenium quantum dots (C-SeQDs); and (ii) to investigate the nano-bio interactions of A-SeQDs and C-SeQDs in MCF-7, HepG2, HeLa, NIH/3T3, L929 cells and BRL-3A cells. It was found that A-SeQDs could induce the mitochondria-mediated apoptosis, necrosis and death of cells, while C-SeQDs had much weaker effects. This polymorphs-dependent anti-proliferative activity of nano-selenium was scarcely reported. Further investigation demonstrated that A-SeQDs could differentially regulate 61 proteins and several pathways related to stress response, protein synthesis, cell migration and cell cycle, including “p38 MAPK Signaling”, “p53 Signaling”, “14-3-3-mediated Signaling”, “p70S6K Signaling” and “Protein Ubiquitination Pathway”. This was the first report to demonstrate the involvement of protein synthesis and post-translational modification pathways in the anti-proliferative activity associated with NMs. Compared with previously fragmentary studies, this study use a nanomics approach combining bioinformatics and proteomics to systematically investigate the nano-bio interactions of selenium nanoparticles in cancer cells.

Selenium effect on ischemia-reperfusion injury of gastrocnemius muscle in adult rats.

PubMed

Gholami, Mohammadreza; Zendedel, Abolfazl; Khanipour khayat, Zahra; Ghanad, Kourosh; Nazari, Afshin; Pirhadi, Atieh

2015-04-01

Selenium is a trace element that has antioxidant and neuroprotective effects. The aim of this study is to investigate the effects of selenium in reducing ischemia-reperfusion injury of the gastrocnemius muscle. In this experimental study, 80 adult male Wistar rats weighing 250-300 g were divided into ten groups (N = 8 per group). Group 1 is control group (without ischemia-reperfusion). Group 2 received 0.2 mg/kg selenium. Group 3 received ischemia + 3 d reperfusion + 0.2 mg/kg selenium, group 4 received ischemia + 3 d reperfusion + 0.2 mg/kg placebo, group 5 received ischemia + 7 d reperfusion + 0.2 mg/kg selenium, group 6 received ischemia + 7 d reperfusion + 0.2 mg/kg placebo, group 7 received ischemia + 14 d reperfusion + 0.2 mg/kg selenium, group 8 received ischemia + 14 d reperfusion + 0.2 mg/kg placebo, group 9 received ischemia + 28 d reperfusion + 0.2 mg/kg selenium and group 10 received ischemia + 3 d reperfusion + 0.2 mg/kg placebo. External iliac artery blocked for 3 h. After reperfusion, rats killed and gastrocnemius muscle removed, fixed, and tissue processing performed. Samples stained with hematoxylin-eosin for edema evaluation, toluidine blue for mast cell infiltration evaluation and immunohistochemistry for detection TNF-alpha and NF-kappa B proteins. Comparison of mast cell infiltration, edema of the interstitial fluid on the tissue, expression of TNF-alpha protein, and expression of NF-kappa B protein in the groups that received selenium with corresponding placebo group showed that selenium can reduce edema, mast cell infiltration, and TNF-alpha expression and inactivated NF-kappa B. The use of selenium simultaneously with creating ischemia can reduce ischemia-reperfusion injury of the gastrocnemius muscle.

Quality assurance program for the determination of selenium in foods and diets by instrumental neutron activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, W.H.; Chatt, A.

1996-12-31

The biological essentially of selenium for animals was first evidenced in 1957. However, it was not until 1973 that an enzyme called glutathione peroxidase was proven to be a selenoenzyme. At present, selenium is known to be a normal component of several enzymes, proteins, and some aminoacryl transfer nucleic acids. A few selenium compounds have been reported to possess anticarcinogenic properties. There is an increasing interest in understanding the role of selenium in human nutrition and metabolism. Analytical methods are being developed in several laboratories for the determination of total and species-specific selenium in whole blood, serum, urine, soft andmore » hard tissues, food, water, proteins, etc. We have developed several instrumental neutron activation analysis (INAA) methods using the, Dalhousie University SLOWPOKE-2 reactor facility for the determination of parts-per-billion levels of selenium. These methods include cyclic INAA (CINAA) and pseudocyclic INAA (PCINAA) using both conventional and anticoincidence gamma-ray spectrometry. Considering the immense health significance, it is imperative that the selenium levels in foods and diets be measured under an extensive quality assurance program for routine monitoring purposes.« less

Effect of Selenium on Lipid and Amino Acid Metabolism in Yeast Cells.

PubMed

Kieliszek, Marek; Błażejak, Stanisław; Bzducha-Wróbel, Anna; Kot, Anna M

2018-04-19

This article discusses the effect of selenium in aqueous solutions on aspects of lipid and amino acid metabolism in the cell biomass of Saccharomyces cerevisiae MYA-2200 and Candida utilis ATCC 9950 yeasts. The yeast biomass was obtained by using waste products (potato wastewater and glycerol). Selenium, at a dose of 20 mg/L of aqueous solution, affected the differentiation of cellular morphology. Yeast enriched with selenium was characterized by a large functional diversity in terms of protein and amino acid content. The protein content in the biomass of S. cerevisiae enriched with selenium (42.6%) decreased slightly as compared to that in the control sample without additional selenium supplementation (48.4%). Moreover, yeasts of both strains enriched with selenium contained a large amount of glutamic acid, aspartic acid, lysine, and leucine. Analysis of fatty acid profiles in S. cerevisiae yeast supplemented with selenium showed an increase in the unsaturated fatty acid content (e.g., C18:1). The presence of margaric acid (C17:0) and hexadecanoic acid (C17:1) was found in the C. utilis biomass enriched with selenium, in contrast to that of S. cerevisiae. These results indicate that selenium may induce lipid peroxidation, which consequently affects the loss of integrity of the cytoplasmic membrane. Yeast enriched with selenium with optimal amino acid and lipid composition can be used to prepare a novel formula of dietary supplements, which can be applied directly to various diets for both humans and animals.

Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma

PubMed Central

Chen, Fasheng; Chen, Chen; Qu, Yangang; Xiang, Hua; Ai, Qingxiu; Yang, Fei; Tan, Xueping; Zhou, Yi; Jiang, Guang; Zhang, Zixiong

2016-01-01

Abstract Background: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. Methods: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. Results: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. Conclusion: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis. PMID:27583873

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

PubMed

Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wu, Xiaofang; Shi, Xiaowei; Ma, Jing; Guo, Xiong

2016-03-01

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney. Copyright © 2015 Elsevier GmbH. All rights reserved.

"Omics" of Selenium Biology: A Prospective Study of Plasma Proteome Network Before and After Selenized-Yeast Supplementation in Healthy Men.

PubMed

Sinha, Indu; Karagoz, Kubra; Fogle, Rachel L; Hollenbeak, Christopher S; Zea, Arnold H; Arga, Kazim Y; Stanley, Anne E; Hawkes, Wayne C; Sinha, Raghu

2016-04-01

Low selenium levels have been linked to a higher incidence of cancer and other diseases, including Keshan, Chagas, and Kashin-Beck, and insulin resistance. Additionally, muscle and cardiovascular disorders, immune dysfunction, cancer, neurological disorders, and endocrine function have been associated with mutations in genes encoding for selenoproteins. Selenium biology is complex, and a systems biology approach to study global metabolomics, genomics, and/or proteomics may provide important clues to examining selenium-responsive markers in circulation. In the current investigation, we applied a global proteomics approach on plasma samples collected from a previously conducted, double-blinded placebo controlled clinical study, where men were supplemented with selenized-yeast (Se-Yeast; 300 μg/day, 3.8 μmol/day) or placebo-yeast for 48 weeks. Proteomic analysis was performed by iTRAQ on 8 plasma samples from each arm at baseline and 48 weeks. A total of 161 plasma proteins were identified in both arms. Twenty-two proteins were significantly altered following Se-Yeast supplementation and thirteen proteins were significantly changed after placebo-yeast supplementation in healthy men. The differentially expressed proteins were involved in complement and coagulation pathways, immune functions, lipid metabolism, and insulin resistance. Reconstruction and analysis of protein-protein interaction network around selected proteins revealed several hub proteins. One of the interactions suggested by our analysis, PHLD-APOA4, which is involved in insulin resistance, was subsequently validated by Western blot analysis. Our systems approach illustrates a viable platform for investigating responsive proteomic profile in 'before and after' condition following Se-Yeast supplementation. The nature of proteins identified suggests that selenium may play an important role in complement and coagulation pathways, and insulin resistance.

Serum levels of Selenium and C-reactive protein in comatose patients with severe traumatic brain injury during the first week of hospitalization: case-control study.

PubMed

Belatar, Bahia; Laidi, Fatna; Abidi, Abdelah El; Eljaoudi, Rachid; Mamouch, Fouzia; Kabbaj, Saad; Maazouzi, Wajdi

2018-01-01

Mortality and morbidity related to traumatic brain injuries still remain high in patients. Many authors reported the importance of Selenium in maintaining the integrity of brain functions. This fact is supported by clinical evidence that therapy with selenium supplementation could help patients suffering from brain disorders like neurodegenerative diseases. The aim of our study was to assess the relationship between Selenium concentration in serum and evolution of comatose patients with severe traumatic brain injury, in the first week of admission, and the correlation between selenium and C-reactive protein. This case-control study was conducted with 64 comatose patients with TBI, in the Department of Anesthesiology and Reanimation, IbnSina University Hospital and Hospital of specialties in Rabat-Morocco, and healthy volunteers recruited in Blood transfusion center of Rabat. Blood sampling was collected from TBI patients, in the first week (3h after admission and each 48h during one week), and from healthy volunteers one time. Concentration of Se in serum was determined by electrochemical atomic absorption spectrometry. Statistical analysis was performed using Statistical software (SPSS) and the cases and controls were compared using the Mann-Whitney U test. A P-value < 0.05 was considered to be statistically significant. Comparison selenium concentration in the first day (D0), third day (D2) and fifth day according to the death and survival statue in patients did not show statistical significance (p > 0.05). Selenium concentration of D0 in patients and Selenium concentration in control group also did not show statistical significance (p > 0.05). Similarly, we did not report a correlation between selenium and C-reactive protein. According to our data selenium and CRP may not play a role in progression of coma state in patients with severe traumatic brain injury.

Interplay between Selenium Levels and Replicative Senescence in WI-38 Human Fibroblasts: A Proteomic Approach.

PubMed

Hammad, Ghania; Legrain, Yona; Touat-Hamici, Zahia; Duhieu, Stéphane; Cornu, David; Bulteau, Anne-Laure; Chavatte, Laurent

2018-01-20

Selenoproteins are essential components of antioxidant defense, redox homeostasis, and cell signaling in mammals, where selenium is found in the form of a rare amino acid, selenocysteine. Selenium, which is often limited both in food intake and cell culture media, is a strong regulator of selenoprotein expression and selenoenzyme activity. Aging is a slow, complex, and multifactorial process, resulting in a gradual and irreversible decline of various functions of the body. Several cellular aspects of organismal aging are recapitulated in the replicative senescence of cultured human diploid fibroblasts, such as embryonic lung fibroblast WI-38 cells. We previously reported that the long-term growth of young WI-38 cells with high (supplemented), moderate (control), or low (depleted) concentrations of selenium in the culture medium impacts their replicative lifespan, due to rapid changes in replicative senescence-associated markers and signaling pathways. In order to gain insight into the molecular link between selenium levels and replicative senescence, in the present work, we have applied a quantitative proteomic approach based on 2-Dimensional Differential in-Gel Electrophoresis (2D-DIGE) to the study of young and presenescent cells grown in selenium-supplemented, control, or depleted media. Applying a restrictive cut-off (spot intensity ±50% and a p value < 0.05) to the 2D-DIGE analyses revealed 81 differentially expressed protein spots, from which 123 proteins of interest were identified by mass spectrometry. We compared the changes in protein abundance for three different conditions: (i) spots varying between young and presenescent cells, (ii) spots varying in response to selenium concentration in young cells, and (iii) spots varying in response to selenium concentration in presenescent cells. Interestingly, a 72% overlap between the impact of senescence and selenium was observed in our proteomic results, demonstrating a strong interplay between selenium, selenoproteins, and replicative senescence.

Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

PubMed

Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

2018-04-01

Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of selenium-containing proteins in HEK 293 kidney cells using multiple chromatographies, LC-ICPMS and nano-LC-ESIMS.

PubMed

Chitta, Karnakar R; Landero-Figueroa, Julio A; Kodali, Phanichand; Caruso, Joseph A; Merino, Edward J

2013-09-30

Our previous studies using HeLa and HEK 293 cells demonstrated that selenomethionine, SeMet, exerts more of an antagonistic effect on arsenic than other selenium species. These studies attributed the antagonistic effect of SeMet to decreased levels of reactive oxygen species, ROS, changes in protein phosphorylation and possible incorporation of SeMet into proteins. The present study employs a metallomics approach to identify the selenium-containing proteins in HEK 293 cells raised with SeMet. The proteins were screened and separated using two dimensional high performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry (ICPMS), size exclusion chromatography (SEC) and reversed-phase chromatography (RPC). The Se-containing proteins were identified by peptide mapping using nano-HPLC-Chip-electrospray ionization mass spectrometry (ESIMS). Copyright © 2013 Elsevier B.V. All rights reserved.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

PubMed

Cao, Nan; Li, Wanyan; Li, Bingxin; Tian, Yunbo; Xu, Danning

2017-12-01

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese. © 2017 Japanese Society of Animal Science.

Involvement of Superoxide Dismutases in the Response of Escherichia coli to Selenium Oxides

PubMed Central

Bébien, Magali; Lagniel, Gilles; Garin, Jérôme; Touati, Danièle; Verméglio, André; Labarre, Jean

2002-01-01

Selenium can provoke contrasting effects on living organisms. It is an essential trace element, and low concentrations have beneficial effects, such as the reduction of the incidence of cancer. However, higher concentrations of selenium salts can be toxic and mutagenic. The bases for both toxicity and protection are not clearly understood. To provide insights into these mechanisms, we analyzed the proteomic response of Escherichia coli cells to selenate and selenite treatment under aerobic conditions. We identified 23 proteins induced by both oxides and ca. 20 proteins specifically induced by each oxide. A striking result was the selenite induction of 8 enzymes with antioxidant properties, particularly the manganese and iron superoxide dismutases (SodA and SodB). The selenium inductions of sodA and sodB were controlled by the transcriptional regulators SoxRS and Fur, respectively. Strains with decreased superoxide dismutase activities were severely impaired in selenium oxide tolerance. Pretreatment with a sublethal selenite concentration triggered an adaptive response dependent upon SoxRS, conferring increased selenite tolerance. Altogether, our data indicate that superoxide dismutase activity is essential for the cellular defense against selenium salts, suggesting that superoxide production is a major mechanism of selenium toxicity under aerobic conditions. PMID:11872706

Study of Highly Selective and Efficient Thiol Derivatization using Selenium Reagents by Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Kehua; Zhang, Yun W.; Tang, Bo

2010-08-15

Biological thiols are critical physiological components and their detection often involves derivatization. This paper reports a systemic mass spectrometry (MS) investigation of the cleavage of Se-N bond by thiol to form a new Se-S bond, the new selenium chemistry for thiol labeling. Our data shows that the reaction is highly selective, rapid, reversible and efficient. For instance, among twenty amino acids, only cysteine was found to be reactive with Se-N containing reagents and the reaction takes place in seconds. By adding dithiothreitol (DTT), the newly formed Se-S bond of peptides/proteins can be reduced back to free thiol. The high selectivitymore » and excellent reversibility of the reaction provide potential of using this chemistry for selective identification of thiol compounds or enriching and purifying thiol peptides/proteins. In addition, the derivatized thiol peptides have interesting dissociation behavior, which is tunable using different selenium reagents. For example, by introducing an adjacent nucleophilic group into the selenium reagent in the case of using ebselen, the reaction product of ebselen with glutathione (GSH) is easy to lose the selenium tag upon collision-induced dissociation (CID), which is useful to "fish out" those peptides containing free cysteine residues by precursor ion scan. By contrast, the selenium tag of N-(phenylseleno) phthalimide reagent can be stable and survive in CID process, which would be of value in pinpointing thiol location using a top-down proteomic approach. Also, the high conversion yield of the reaction allows the counting of total number of thiol in proteins. We believe that ebselen or N-(phenylseleno) phthalimide as tagging thiol-protein reagents will have important applications in both qualitative and quantitative analysis of different thiol-proteins derived from living cells by MS method.« less

Selenium protein identification and profiling by mass spectrometry: A tool to assess progression of cardiomyopathy in a whale model.

PubMed

Bryan, Colleen E; Bossart, Gregory D; Christopher, Steven J; Davis, W Clay; Kilpatrick, Lisa E; McFee, Wayne E; O'Brien, Terrence X

2017-12-01

Non-ischemic cardiomyopathy is a leading cause of congestive heart failure and sudden cardiac death in humans and in some cases the etiology of cardiomyopathy can include the downstream effects of an essential element deficiency. Of all mammal species, pygmy sperm whales (Kogia breviceps) present the greatest known prevalence of cardiomyopathy with more than half of examined individuals indicating the presence of cardiomyopathy from gross and histo-pathology. Several factors such as genetics, infectious agents, contaminants, biotoxins, and inappropriate dietary intake (vitamins, selenium, mercury, and pro-oxidants), may contribute to the development of idiopathic cardiomyopathy in K. breviceps. Due to the important role Se can play in antioxidant biochemistry and protein formation, Se protein presence and relative abundance were explored in cardiomyopathy related cases. Selenium proteins were separated and detected by multi-dimension liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS), Se protein identification was performed by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS), and Se protein profiles were examined in liver (n=30) and heart tissue (n=5) by SEC/UV/ICP-MS detection. Data collected on selenium proteins was evaluated in the context of individual animal trace element concentration, life history, and histological information. Selenium containing protein peak profiles varied in presence and intensity between animals with no pathological findings of cardiomyopathy and animals exhibiting evidence of cardiomyopathy. In particular, one class of proteins, metallothioneins, was found to be associated with Se and was in greater abundance in animals with cardiomyopathy than those with no pathological findings. Profiling Se species with SEC/ICP-MS proved to be a useful tool to identify Se protein pattern differences between heart disease stages in K. breviceps and an approach similar to this may be applied to other species to study Se protein associations with cardiomyopathy. Published by Elsevier GmbH.

Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial.

PubMed

Leo, M; Bartalena, L; Rotondo Dottore, G; Piantanida, E; Premoli, P; Ionni, I; Di Cera, M; Masiello, E; Sassi, L; Tanda, M L; Latrofa, F; Vitti, P; Marcocci, C; Marinò, M

2017-03-01

In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days. Baseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT 3 and FT 4 , with no difference between groups. Heart rate, SHBG and symptoms of hyperthyroidism decreased, whereas total cholesterol increased in both groups with no difference between groups. Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.

Selenium fertilization on lentil (Lens culinaris Medikus) grain yield, seed selenium concentration, and antioxidant activity

USDA-ARS?s Scientific Manuscript database

Selenium (Se) is an essential element for mammals but has not been considered as an essential element for higher plants. Lentil (Lens culinaris Medik.) is a cool season food legume rich in protein and a range of micronutrients including minerals (iron and zinc), folates, and carotenoids. The objecti...

Assessment of selenium bioavailability from naturally produced high-selenium soy foods in selenium-deficient rats.

PubMed

Yan, Lin; Reeves, Philip G; Johnson, LuAnn K

2010-10-01

We assessed the bioavailability of selenium (Se) from a protein isolate and tofu (bean curd) prepared from naturally produced high-Se soybeans. The Se concentrations of the soybeans, the protein isolate and tofu were 5.2±0.2, 11.4±0.1 and 7.4±0.1mg/kg, respectively. Male weanling Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet (4.1μg Se/kg) for 56 days, and then they were replenished with Se for an additional 50 days by feeding them the same diet containing 14, 24 or 30 μg Se/kg from the protein isolate or 13, 23 or 31 μg Se/kg from tofu, respectively. l-Selenomethionine (SeMet) was used as a reference. Selenium bioavailability was determined on the basis of the restoration of Se-dependent enzyme activities and tissue Se concentrations in Se-depleted rats, comparing those responses for the protein isolate and tofu to those for SeMet by using a slope-ratio method. Dietary supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in glutathione peroxidase activities in blood and liver and in thioredoxin reductase activity in liver. Furthermore, supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in the Se concentrations of plasma, liver, muscle and kidneys. These results indicated an overall bioavailability of approximately 101% for Se from the protein isolate and 94% from tofu, relative to SeMet. We conclude that Se from naturally produced high-Se soybeans is highly bioavailable in this model and that high-Se soybeans may be a good dietary source of Se. Published by Elsevier GmbH.

Clinical relevance of trace element measurement in patients on initiation of parenteral nutrition.

PubMed

Salota, Rashim; Omar, Sohail; Sherwood, Roy A; Raja, Kishor; Vincent, Royce P

2016-11-01

Background and Aims Serum zinc, copper and selenium are measured in patients prior to commencing on parenteral nutrition; however, their interpretation can be difficult due to acute phase reactions. We assessed (i) the relationship of raised C-reactive protein with trace elements and albumin (ii) benefits of measuring trace elements when C-reactive protein is raised in patients requiring short-term parenteral nutrition. Methods Samples were collected for zinc, copper, selenium and albumin at baseline and then every two weeks and correlated with C-reactive protein results in patients on parenteral nutrition. Results were categorized into four groups based on the C-reactive protein concentrations: (i) <20 mg/L, (ii) 20-39 mg/L, (iii) 40-79 mg/L and (iv) ≥80 mg/L. Results In 166 patients, zinc, selenium and albumin correlated (Spearman's) negatively with C-reactive protein; r = -0.26, P < 0.001 (95% CI -0.40 to -0.11), r = -0.44, P < 0.001 (-0.56 to -0.29) and r = -0.22 P = 0.005 (-0.36 to -0.07), respectively. Copper did not correlate with C-reactive protein (r = 0.09, P = 0.25 [-0.07 to 0.25]). Comparison of trace elements between the four groups showed no difference in zinc and copper (both P > 0.05), whereas selenium and albumin were lower in the group with C-reactive protein > 40 mg/L ( P < 0.05). Conclusion In patients on short-term parenteral nutrition, measurement of C-reactive protein is essential when interpreting zinc and selenium but not copper results. Routine measurement of trace elements prior to commencing parenteral nutrition has to be considered on an individual basis in patients with inflammation.

Rapid, room-temperature synthesis of amorphous selenium/protein composites using Capsicum annuum L extract

NASA Astrophysics Data System (ADS)

Li, Shikuo; Shen, Yuhua; Xie, Anjian; Yu, Xuerong; Zhang, Xiuzhen; Yang, Liangbao; Li, Chuanhao

2007-10-01

We describe the formation of amorphous selenium (α-Se)/protein composites using Capsicum annuum L extract to reduce selenium ions (SeO32-) at room temperature. The reaction occurs rapidly and the process is simple and easy to handle. A protein with a molecular weight of 30 kDa extracted from Capsicum annuum L not only reduces the SeO32- ions to Se0, but also controls the nucleation and growth of Se0, and even participates in the formation of α-Se/protein composites. The size and shell thickness of the α-Se/protein composites increases with high Capsicum annuum L extract concentration, and decreases with low reaction solution pH. The results suggest that this eco-friendly, biogenic synthesis strategy could be widely used for preparing inorganic/organic biocomposites. In addition, we also discuss the possible mechanism of the reduction of SeO32- ions by Capsicum annuum L extract.

A subchronic toxicity study of elemental Nano-Se in Sprague-Dawley rats.

PubMed

Jia, X; Li, N; Chen, J

2005-03-11

The subchronic toxicity of Nano-Se was compared with selenite and high-selenium protein in rats. Groups of Sprague-Dawley rats (12 males and 12 females per group) were fed diets containing Nano-Se, selenite and high-selenium protein at concentrations of 0, 2, 3, 4 and 5 ppm Se, respectively, for 13 weeks. Clinical observations were made and body weight and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry determination. Histopathological examination was performed on selected tissues. At the two higher doses (4 and 5 ppm Se), significant abnormal changes were found in body weight, hematology, clinical chemistry, relative organ weights and histopathology parameters. However, the toxicity was more pronounced in the selenite and high-selenium protein groups than the Nano-Se group. At the dose of 3 ppm Se, significant growth inhibition and degeneration of liver cells were found in the selenite and high-selenium protein groups. No changes attributable to administration of Nano-Se at the dose of 3 ppm Se were found. Taken together, the no-observed-adverse-effect level (NOAEL) of Nano-Se in male and female rats was considered to be 3 ppm Se, equivalent to 0.22 mg/kg bw/day for males and 0.33 mg/kg bw/day for females. On the other hand, the NOAELs of selenite and high-selenium protein in males and females were considered to be 2 ppm Se, equivalent to 0.14 mg/kg bw/day for males and 0.20 mg/kg bw/day for females. In addition, studies have shown that Nano-Se has a similar bioavailability in rat, and much less acute toxicity in mice compared with selenite. In conclusion, Nano-Se is less toxic than selenite and high-selenium protein in the 13-week rat study.

Selenoprotein K Binds Multiprotein Complexes and Is Involved in the Regulation of Endoplasmic Reticulum Homeostasis*

PubMed Central

Shchedrina, Valentina A.; Everley, Robert A.; Zhang, Yan; Gygi, Steven P.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Selenoprotein K (SelK) is an 11-kDa endoplasmic reticulum (ER) protein of unknown function. Herein, we defined a new eukaryotic protein family that includes SelK, selenoprotein S (SelS), and distantly related proteins. Comparative genomics analyses indicate that this family is the most widespread eukaryotic selenoprotein family. A biochemical search for proteins that interact with SelK revealed ER-associated degradation (ERAD) components (p97 ATPase, Derlins, and SelS). In this complex, SelK showed higher affinity for Derlin-1, whereas SelS had higher affinity for Derlin-2, suggesting that these selenoproteins could determine the nature of the substrate translocated through the Derlin channel. SelK co-precipitated with soluble glycosylated ERAD substrates and was involved in their degradation. Its gene contained a functional ER stress response element, and its expression was up-regulated by conditions that induce the accumulation of misfolded proteins in the ER. Components of the oligosaccharyltransferase complex (ribophorins, OST48, and STT3A) and an ER chaperone, calnexin, were found to bind SelK. A glycosylated form of SelK was also detected, reflecting its association with the oligosaccharyltransferase complex. These data suggest that SelK is involved in the Derlin-dependent ERAD of glycosylated misfolded proteins and that the function defined by the prototypic SelK is the widespread function of selenium in eukaryotes. PMID:22016385

Selenium uptake and assessment of the biochemical changes in Arthrospira (Spirulina) platensis biomass during the synthesis of selenium nanoparticles.

PubMed

Zinicovscaia, I; Chiriac, T; Cepoi, L; Rudi, L; Culicov, O; Frontasyeva, M; Rudic, V

2017-01-01

The process of selenium uptake by biomass of the cyanobacterium Arthrospira (Spirulina) platensis was investigated by neutron activation analysis at different selenium concentrations in solution and at different contact times. Experimental data showed good fit with the Freundlich adsorption isotherm model, with a regression coefficient value of 0.99. In terms of absorption dependence on time, the maximal selenium content was adsorbed in the first 5 min of interaction without significant further changes. It was also found that A. platensis biomass forms spherical selenium nanoparticles. Biochemical analysis was used to assess the changes in the main components of spirulina biomass (proteins, lipids, carbohydrates, and phycobilin) during nanoparticle formation.

Deproteinization assessment using isotopically enriched compounds to trace the coprecipitation of low-molecular-weight selenium species with proteins.

PubMed

Godin, Simon; Bouzas-Ramos, Diego; Fontagné-Dicharry, Stéphanie; Bouyssière, Brice; Bueno, Maïté

2017-08-01

Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic ( 77 Se-selenite) and organic zwitterionic ( 76 Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics. Copyright © 2017 Elsevier Inc. All rights reserved.

A functional variant in NKX3.1 associated with prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Martinez, Erin E.; Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.; Fowke, Jay H.; Klein, Eric A.; Abdulkadir, Sarki A.

2014-01-01

NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knock-out mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort sub-study (1,866 cases; 3135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared to placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk (HR 1.676, 95% CI 1.011-2.777, p=0.045) and low grade prostate cancer risk (HR 1.811, 95% CI 1.016-3.228, p=0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR 1.450, 95% CI 1.117-1.882, p=0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents. PMID:24894197

Selenium bioaccessibility and speciation in biofortified Pleurotus mushrooms grown on selenium-rich agricultural residues.

PubMed

Bhatia, Poonam; Aureli, Federica; D'Amato, Marilena; Prakash, Ranjana; Cameotra, Swaranjit Singh; Nagaraja, Tejo Prakash; Cubadda, Francesco

2013-09-01

Cultivation of saprophytic fungi on selenium-rich substrates can be an effective means to produce selenium-fortified food. Pleurotus florida, an edible species of oyster mushrooms, was grown on wheat straw from the seleniferous belt of Punjab (India) and its potential to mobilize and accumulate selenium from the growth substrate was studied. Selenium concentration in biofortified mushrooms was 800 times higher compared with control samples grown on wheat straw from non selenium-rich areas (141 vs 0.17 μg Se g(-1) dry weight). Seventy-five percent of the selenium was extracted after in vitro simulated gastrointestinal digestion and investigation of the selenium molecular fractions by size exclusion HPLC-ICP-MS revealed that proteins and any other high molecular weight selenium-containing molecule were hydrolyzed to peptides and low molecular weight selenocompounds. Analysis of the gastrointestinal hydrolysates by anion exchange HPLC-ICP-MS showed that the bioaccessible selenium was mainly present as selenomethionine, a good bioavailable source of selenium, which accounted for 73% of the sum of the detected species. This study demonstrates the feasibility of producing selenium-biofortified edible mushrooms using selenium-rich agricultural by-products as growth substrates. The proposed approach can be used to evaluate whether selenium-contaminated plant waste materials harvested from high-selenium areas may be used to produce selenium-biofortified edible mushrooms based on the concentration, bioaccessibility and speciation of selenium in the mushrooms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mechanism of bio molecule stabilized selenium nanoparticles against oxidation process and Clostridium Botulinum.

PubMed

Tareq, Foysal Kabir; Fayzunnesa, Mst; Kabir, Md Shahariar; Nuzat, Musrat

2018-02-01

The bio molecules from plant leaf extract utilized in the preparation of selenium material at the nano scale. The selenium ion was reduced to selenium nanoparticles in the presence of molecule residue of the plant leaf extract. The bio molecule stabilized selenium nanoparticles were grown gradually in the reaction mixture. The selenium nanoparticles were characterized using atomic absorption spectroscopy, fourier transform inferred spectroscopy, X-ray diffraction, scanning electronic microscope and transmission electronic microscope. The selenium nanoparticles were synthesized successfully as the nano-crystalline pure hexagonal phase and the size range of 26-41 nm with spherical in shape. The activity and mechanism of nanoparticles suggested that the selenium nanoparticles are causes of leakage of reducing sugars and protein of pathogens membrane cell. The selenium nano are responsible for death and fully inhibited the microbial growth of pathogen. The bio molecule stabilized selenium nanoparticles were also investigated for the antioxidant agent. Selenium nanoparticles showed scavenging activity up to 94.48%. These results recommended that the advantages of using this method for synthesis of selenium nanoparticles with excellent antioxidant and antimicrobial mechanism and activity, which can be used as the antioxidant and antibiotic agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

NASA Astrophysics Data System (ADS)

Methogo, Ruth Menque; Dansette, Patrick M.; Klarskov, Klaus

2007-12-01

A combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase.

Selenium toxicity in plants and its detoxification by phosphorus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, M.; Singh, N.

1978-11-01

A study was undertaken to determine selenium toxicity and the effect of phosphorus application on selenium in wheat (Triticum aestivum). Selenium in a compound was applied at 0, 2.5, 5, and 10 ppm to wheat in a greenhouse using sandy soil. Phosphorus in a compound was applied at 0, 50, and 100 ppm to the experimental plants. Sunflower (Helianthus annuus) was grown after wheat to determine the residual effect of selenium and phosphorus. Results indicated that high amounts (2.5 ppm and above) of added and residual selenium in soil decreased the growth of wheat and sunflower, decreased the absorption ofmore » zinc, copper, iron, manganese, sulfur, and nitrogen, and decreased the synthesis of nucleic acids, chlorophyll, and protein. The application of phosphorus decreased the harmful effects of selenium and increased all the above parameters. (3 graphs, 21 references, 4 tables)« less

Production of Selenoprotein P (Sepp1) by Hepatocytes Is Central to Selenium Homeostasis*

PubMed Central

Hill, Kristina E.; Wu, Sen; Motley, Amy K.; Stevenson, Teri D.; Winfrey, Virginia P.; Capecchi, Mario R.; Atkins, John F.; Burk, Raymond F.

2012-01-01

Sepp1 is a widely expressed extracellular protein that in humans and mice contains 10 selenocysteine residues in its primary structure. Extra-hepatic tissues take up plasma Sepp1 for its selenium via apolipoprotein E receptor-2 (apoER2)-mediated endocytosis. The role of Sepp1 in the transport of selenium from liver, a rich source of the element, to peripheral tissues was studied using mice with selective deletion of Sepp1 in hepatocytes (Sepp1c/c/alb-cre+/− mice). Deletion of Sepp1 in hepatocytes lowered plasma Sepp1 concentration to 10% of that in Sepp1c/c mice (controls) and increased urinary selenium excretion, decreasing whole-body and tissue selenium concentrations. Under selenium-deficient conditions, Sepp1c/c/alb-cre+/− mice accumulated selenium in the liver at the expense of extra-hepatic tissues, severely worsening clinical manifestations of dietary selenium deficiency. These findings are consistent with there being competition for metabolically available hepatocyte selenium between the synthesis of selenoproteins and the synthesis of selenium excretory metabolites. In addition, selenium deficiency down-regulated the mRNA of the most abundant hepatic selenoprotein, glutathione peroxidase-1 (Gpx1), to 15% of the selenium-replete value, while reducing Sepp1 mRNA, the most abundant hepatic selenoprotein mRNA, only to 61%. This strongly suggests that Sepp1 synthesis is favored in the liver over Gpx1 synthesis when selenium supply is limited, directing hepatocyte selenium to peripheral tissues in selenium deficiency. We conclude that production of Sepp1 by hepatocytes is central to selenium homeostasis in the organism because it promotes retention of selenium in the body and effects selenium distribution from the liver to extra-hepatic tissues, especially under selenium-deficient conditions. PMID:23038251

Selenium status and fungi in the protein-losing enteropathy of persistent diarrhea.

PubMed

Dwipoerwantoro, Pramita G; Lukito, Widjaja; Aulia, Diana; Arnaud, Josiane; Roussel, Anne-Marie

2017-06-01

A vicious cycle of infection, malabsorption, and malnutrition has been implicated in the perpetuation of diarrheal disease. This study examined whether persistent diarrhea is associated with changes in selenium status and stool alpha-1 antitrypsin (AAT) concentration. This cross-sectional study included 30 children aged 1-12 years with persistent diarrhea who were hospitalized in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, and 30 apparently healthy children who were matched by age and sex and lived in a rural area of Jakarta. Clinical examinations, blood routine tests, erythrocyte glutathione peroxidase (GPX) activity and plasma selenium levels as well as AAT in fresh stool samples were performed in all the subjects. Of 30 children with persistent diarrhea, 17 had moderate malnutrition and 13 had severe malnutrition. The mean plasma selenium was significantly lower in children with persistent diarrhea than in children without diarrhea (86.0 μg/L [95% CI: 76.1-95.9] vs 110 μg/L [95% CI: 104-116, p<0.0001). The mean stool AAT concentration was significantly higher in children with persistent diarrhea than in those without diarrhea (115 mg/dL [95% CI: 38.5-191] vs 16 mg/dL [95% CI: 4.0-13.5, p<0.0001]). Selenium correlated with AAT (p=0.05). Fecal fungi were persistently present. Although selenium status in both groups was optimal for the obtained plasma GPX activity, children with persistent diarrhea exhibited lower plasma selenium levels. This study suggests that the decrease in the plasma selenium level may be the consequence of protein loss and that fungi may be involved.

[Studies of bioavailability of different food sources of selenium in experiment].

PubMed

Egorova, E A; Gmoshinskiĭ, I V; Zorin, S I; Mazo, V K

2006-01-01

The selenium bioavailability in selenium enriched Spirulina (Arthrospira platensis), phycocyanin containing (Se-PC) protein isolate, separated from this micro algae and in sodium selenite was studied and compared in rats. The daily dose of selenium per one animal was 5 microgram in all experimental groups. The average selenium levels in blood serum and liver of animals that received sodium selenite during 14 days were the highest. The average selenium level in blood serum of animals fed with selenium enriched Spirulina platensis after 14 days of receiving was the same with the control group, but the average concentration of selenium in their liver was rather high and close to this parameter of sodium selenite animal group. The animals which were fed with Se-PC showed better results. Their average selenium level in blood serum was higher than in Spirulina group, but lower than in sodium selenite group. The average concentration of selenium in the liver of these animals was the same with sodium selenite animal group. As regards to animals that were fed with selenium enriched Spirulina, Se-PC and sodium selenite for 21 days, the average selenium levels ratio in their blood serum and liver was higher than in control group, but these results were not significantly different among each other. The concentrations of selenium in seminal glands in all groups of animals including control group both after 14 and 21 days feeding were close to each other.

Glutathione peroxidase response in tissues of rats fed diets containing fish protein concentrate prepared from shark flesh of known mercury and selenium contents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thrower, S.J.; Andrewartha, K.A.

1981-01-01

Studies have been reported using experimental animals and synthetic diets containing selenium and mercury compounds to demonstrate detoxification of mercury by selenium. The mechanism of detoxification remains obscure. Most experiments have involved the use of high levels of both elements and relied on the observation of gross symptoms. The measurement of enzyme systems may be useful in detecting effects of mercury at a lower, subclinical level and in elucidating the biochemistry of mercury/selenium interactions. The activity of the selenoenzyme glutathione peroxidase (GSH-Px) in rats is dependent on dietary selenium and attempts have been made to use this enzyme as anmore » indicator of mercury/selenium interactions. The research described in this paper was designed to investigate the effect of mercury, in the form and amounts which occur naturally in seafood, on the availability of selenium at levels approximating the nutritional requirement. In anticipation of mercury lowering the GSH-Px response a range of selenium concentrations was used, from nutritional deficiency to three times the nutritional requirement.« less

Purification and characterization of selenium-containing phycocyanin from selenium-enriched Spirulina platensis.

PubMed

Chen, Tianfeng; Wong, Yum-Shing; Zheng, Wenjie

2006-11-01

A fast protein liquid chromatographic method for purification of selenium-containing phycocyanin (Se-PC) from selenium-enriched Spirulina platensis was described in this study. The purification procedures involved fractionation by ammonium sulfate precipitation, DEAE-Sepharose ion-exchange chromatography and Sephacry S-300 size exclusion chromatography. The purity ratio (A620/A280) and the separation factor (A620/A655) of the purified Se-PC were 5.12 and 7.92, respectively. The Se concentration of purified Se-PC was 496.5 microg g(-1) protein, as determined by ICP-AES analysis. The purity of the Se-PC was further characterized by UV-VIS and fluorescence spectrometry, SDS-PAGE, RP-HPLC and gel filtration HPLC. The apparent molecular mass of the native Se-PC determined by gel filtration HPLC was 109 kDa, indicating that the protein existed as a trimer. SDS-PAGE of the purified Se-PC yielded two major bands corresponding to the alpha and beta subunits. A better separation of these two subunits was obtained by RP-HPLC. Identification of the alpha and beta subunits separated by SDS-PAGE and RP-HPLC was achieved by peptide mass fingerprinting (PMF) using MALDI-TOF-TOF mass spectrometry.

Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

PubMed Central

Weekley, Claire M.; Aitken, Jade B.; Finney, Lydia; Vogt, Stefan; Witting, Paul K.; Harris, Hugh H.

2013-01-01

Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS) and X-ray fluorescence microscopy (XFM). The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed. PMID:23698165

Scaffold of Selenium Nanovectors and Honey Phytochemicals for Inhibition of Pseudomonas aeruginosa Quorum Sensing and Biofilm Formation.

PubMed

Prateeksha; Singh, Braj R; Shoeb, M; Sharma, S; Naqvi, A H; Gupta, Vijai K; Singh, Brahma N

2017-01-01

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro . Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

[Is plasma selenium correlated to transthyretin levels in critically ill patients?

PubMed

Freitas, Renata G B O N; Nogueira, Roberto Jose Negrão; Cozzolino, Silvia Maria Franciscato; Vasques, Ana Carolina Junqueira; Ferreira, Matthew Thomas; Hessel, Gabriel

2017-06-05

Selenium is an essential trace element, but critically ill patients using total parenteral nutrition (PN) do not receive selenium because this mineral is not commonly offered. Threfore, the eval uation of plasma selenium levels is very important for treating or preventing this deficiency. Recent studies have shown that transthyretin may reflect the selenium intake and could be considered a biomarker. However, this issue is still little explored in the literature. This study aims to investigate the correlation of transthyretin with the plasma selenium of critically ill patients receiving PN. This was a prospective cohort study with 44 patients using PN without selenium. Blood samples were carried out in 3 stages: initial, 7th and 14th day of PN. In order to evaluate the clinical condition and the inflammatory process, albumin, C-reactive protein (CRP), transthyretin, creatinine and HDL cholesterol levels were observed. To assess the selenium status, plasma selenium and glutathione peroxidase (GPx) in whole blood were measured. Descriptive analyses were performed and the ANOVA, Mann-Whitney and Spearman's coefficient tests were conducted; we assumed a significance level of 5%. A positive correlation of selenium with the GPx levels (r = 0.46; p = 0.03) was identified. During two weeks, there was a positive correlation of transthyretin with plasma selenium (r = 0.71; p = 0.05) regardless of the CRP values. Transthyretin may have reflected plasma selenium, mainly because the correlation was verified after the acute phase.

Selenium Characterization In The Global Rice Supply Chain

EPA Science Inventory

For up to 1 billion people worldwide, insufficient dietary intake of selenium (Se) is a serious health constraint. Cereals are the dominant Se source for those on low protein diets, as typified by the global malnourished population. With crop Se content constrained largely by u...

JV Task 96 - Phase 2 - Investigating the Importance of the Mercury-Selenium Interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas Ralston; Laura Raymond

2008-03-01

In order to improve the understanding of the mercury issue, it is vital to study mercury's effects on selenium physiology. While mercury present in the environment or food sources may pose health risks, the protective effects of selenium have not been adequately considered in establishing regulatory policy. Numerous studies report that vulnerability to mercury toxicity is inversely proportional to selenium status or level. However, selenium status has not been considered in the development of the reference dosage levels for mercury exposure. Experimental animals fed low-selenium diets are far more vulnerable to mercury toxicity than animals fed normal selenium, and animalsmore » fed selenium-rich diets are even more resistant. Selenium-dependent enzymes in brain and endocrine tissues can be impaired by excessive mercury exposure, apparently because mercury has an extremely high binding affinity for selenium. When selenium becomes bound to mercury, it is unable to participate in the metabolic cycling of selenoprotein synthesis. Because of mercury-dependent impairments of selenoprotein synthesis, various antioxidant and regulatory functions in brain biochemistry are compromised. This report details a 2-year multiclient-funded research program designed to examine the interactions between mercury and selenium in animal models. The studies explored the effects of dietary intakes of toxic amounts of methylmercury and the protective effects of the normal dietary range of selenium in counteracting mercury toxicity. This study finds that the amounts of selenium present in ocean fish are sufficient to protect against far larger quantities of methylmercury than those present in typical seafoods. Toxic effects of methylmercury exposure were not directly proportional to mercury concentrations in blood, brain, or any other tissues. Instead, mercury toxicity was proportional to molar ratios of mercury relative to selenium. In order to accurately assess risk associated with methylmercury or mercury exposures, mercury-selenium ratios appear to be far more accurate and effective in identifying risk and protecting human and environmental health. This study also finds that methylmercury toxicity can be effectively treated by dietary selenium, preventing the death and progressive disabilities that otherwise occur in methylmercury-treated subjects. Remarkably, the positive response to selenium therapy was essentially equivalent regardless of whether or not toxic amounts of methylmercury were still administered. The findings of the Physiologically Oriented Integration of Nutrients and Toxins (POINT) models of the effects of mercury and selenium developed in this project are consistent with the hypothesis that mercury toxicity arises because of mercury-dependent inhibition of selenium availability in brain and endocrine tissues. This appears to occur through synergistic effects of mercury-dependent inhibition of selenium transport to these tissues and selective sequestration of the selenium present in the tissues. Compromised transport of selenium to the brain and endocrine tissues would be particularly hazardous to the developing fetus because the rapidly growing tissues of the child have no selenium reserves. Therefore, maternal consumption of foods with high mercury-selenium ratios is hazardous. In summation, methylmercury exposure is unlikely to cause harm in populations that eat selenium-rich diets but may cause harm among populations that consume certain foods that have methylmercury present in excess of selenium.« less

Effect of Sodium Selenate on Hippocampal Proteome of 3×Tg-AD Mice-Exploring the Antioxidant Dogma of Selenium against Alzheimer's Disease.

PubMed

Iqbal, Javed; Zhang, Kaoyuan; Jin, Na; Zhao, Yuxi; Liu, Qiong; Ni, Jiazuan; Shen, Liming

2018-04-19

Selenium (Se), an antioxidant trace element, is an important nutrient for maintaining brain functions and is reported to be involved in Alzheimer's disease (AD) pathologies. The present study has been designed to elucidate the protein changes in hippocampus of 3×Tg-AD mice after supplementing sodium selenate as an inorganic source of selenium. By using iTRAQ proteomics technology, 113 differentially expressed proteins (DEPs) are found in AD/WT mice with 37 upregulated and 76 downregulated proteins. Similarly, in selenate-treated 3×Tg-AD (ADSe/AD) mice, 115 DEPs are found with 98 upregulated and 17 downregulated proteins. The third group of mice (ADSe/WT) showed 75 DEPs with 46 upregulated and 29 downregulated proteins. Among these results, 42 proteins (40 downregulated and 2 upregulated) in the diseased group showed reverse expression when treated with selenate. These DEPs are analyzed with different bioinformatics tools and are found associated with various AD pathologies and pathways. Based on their functions, selenate-reversed proteins are classified as structural proteins, metabolic proteins, calcium regulating proteins, synaptic proteins, signaling proteins, stress related proteins, and transport proteins. Six altered AD associated proteins are successfully validated by Western blot analysis. This study shows that sodium selenate has a profound effect on the hippocampus of the triple transgenic AD mice. This might be established as an effective therapeutic agent after further investigation.

Selenium Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer

PubMed Central

Yu-Rice, Yi; Edassery, Seby L.; Urban, Nicole; Hellstrom, Ingegerd; Hellstrom, Karl Erik; Deng, Youping; Li, Yan; Luborsky, Judith L.

2016-01-01

Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to Selenium Binding Protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n=41), infertility (n=92) and control (n=87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1 positive sera was higher in POF (p=0.02), irregular ovulation (p=0.001), unexplained causes (p=0.02), late (III–IV) stage OvCa (p=0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I–II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (p=0.04) but not non-serous (p=0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-p53, markers often studied in OvCa. Anti-p53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls, or when combined with anti-p53 and CA125, to identify OvCa was evaluated by comparing the Area Under the Curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC=0.7; p=0.001) or OvCa (AUC=0.67; p=0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-p53 and anti-SBP1 (AUC=0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with development of serous OvCa. PMID:27965399

Strong Poison Revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prince, R.C.; Gailer, J.; Gunson, D.E.

2009-06-04

Selenium in the form of selenocysteine plays an essential role in a number of proteins, but its role in non-enzymatic biochemistry is also important. In this short review we discuss the interactions between inorganic selenium, arsenic and mercury under physiological conditions, especially in the presence of glutathione. This chemistry is obviously important in making the arsenic and mercury unavailable for more toxic interactions, but in the process it suggests that a side-effect of chronic arsenic and/or mercury exposure is likely to be functional selenium deficiency.

Translational Redefinition of UGA Codons Is Regulated by Selenium Availability*

PubMed Central

Howard, Michael T.; Carlson, Bradley A.; Anderson, Christine B.; Hatfield, Dolph L.

2013-01-01

Incorporation of selenium into ∼25 mammalian selenoproteins occurs by translational recoding whereby in-frame UGA codons are redefined to encode the selenium containing amino acid, selenocysteine (Sec). Here we applied ribosome profiling to examine the effect of dietary selenium levels on the translational mechanisms controlling selenoprotein synthesis in mouse liver. Dietary selenium levels were shown to control gene-specific selenoprotein expression primarily at the translation level by differential regulation of UGA redefinition and Sec incorporation efficiency, although effects on translation initiation and mRNA abundance were also observed. Direct evidence is presented that increasing dietary selenium causes a vast increase in ribosome density downstream of UGA-Sec codons for a subset of selenoprotein mRNAs and that the selenium-dependent effects on Sec incorporation efficiency are mediated in part by the degree of Sec-tRNA[Ser]Sec Um34 methylation. Furthermore, we find evidence for translation in the 5′-UTRs for a subset of selenoproteins and for ribosome pausing near the UGA-Sec codon in those mRNAs encoding the selenoproteins most affected by selenium availability. These data illustrate how dietary levels of the trace element selenium can alter the readout of the genetic code to affect the expression of an entire class of proteins. PMID:23696641

The Effect of Selenium Enrichment on Baker s Yeast Proteome

PubMed Central

El-Bayoumy, Karam; Das, Arunangshu; Russell, Stephen; Wolfe, Steven; Jordan, Rick; Renganathan, Kutralanathan; Loughran, Thomas P.; Somiari, Richard

2011-01-01

The use of regular yeast (RY) and selenium-enriched yeast (SEY) as dietary supplement is of interest because the Nutritional Prevention of Cancer (NPC) trial revealed that SEY but not RY decreased the incidence of prostate cancer (PC). Using two-dimensional difference in gel electrophoresis (2D-DIGE) – tandem mass spectrometry (MS/MS) approach, we performed proteomic analysis of RY and SEY to identify proteins that are differentially expressed as a result of selenium enrichment. 2D-DIGE revealed 96 candidate protein spots that were differentially expressed (p≤0.05) between SEY and RY. The 96 spots were selected, sequenced by LC/MS/MS and 37 proteins were unequivocally identified. The 37 identified proteins were verified with ProteinProphet software and mapped to existing Gene Ontology categories. Furthermore, the expression profile of 5 of the proteins with validated or putative roles in the carcinogenesis process, and for which antibodies against human forms of the proteins are available commercially were verified by western analysis. This study provides evidence for the first time that SEY contains higher levels of Pyruvate Kinase, HSP70, and Elongation factor 2 and lower levels of Eukaryotic Translation Initiation Factor 5A-2 and Triosephosphate Isomerase than those found in RY. PMID:22067702

Selenium Nanoparticles for Stress-Resilient Fish and Livestock

NASA Astrophysics Data System (ADS)

Sarkar, Biplab; Bhattacharjee, Surajit; Daware, Akshay; Tribedi, Prosun; Krishnani, K. K.; Minhas, P. S.

2015-09-01

The fisheries and livestock sectors capture the highest share of protein-rich animal food and demonstrate accelerated growth as an agriculture subsidiary. Environmental pollution, climate change, as well as pathogenic invasions exert increasing stress impacts that lead the productivity momentum at a crossroads. Oxidative stress is the most common form of stress phenomenon responsible for the retardation of productivity in fisheries and livestock. Essential micronutrients play a determinant role in combating oxidative stress. Selenium, one of the essential micronutrients, appears as a potent antioxidant with reduced toxicity in its nanoscale form. In the present review, different methods of synthesis and characterization of nanoscale selenium have been discussed. The functional characterization of nano-selenium in terms of its effect on growth patterns, feed digestibility, and reproductive system has been discussed to elucidate the mechanism of action. Moreover, its anti-carcinogenic and antioxidant potentiality, antimicrobial and immunomodulatory efficacy, and fatty acid reduction in liver have been deciphered as the new phenomena of nano-selenium application. Biologically synthesized nano-selenium raises hope for pharmacologically enriched, naturally stable nanoscale selenium with high ecological viability. Hence, nano-selenium can be administered with commercial feeds for improvising stress resilience and productivity of fish and livestock.

Vitamin E and selenium interrelations in the diet of Atlantic salmon (Salmo salar): Gross, histological and biochemical deficiency signs

USGS Publications Warehouse

Poston, Hugh A.; Combs, G.F.; Leibovitz, Louis

1976-01-01

Either simultaneous or separate dietary deficiencies of vitamin E and selenium in Atlantic salmon during first 4 weeks of feeding caused twice the mortality shown in fish fed both supplemental vitamin E (0.5 IU/g dry diet) and selenium (0.1 µg/g). Subsequent dietary repletion with both vitamin E and selenium significantly reduced mortality during the following 2 weeks. Larger salmon (0.9 g initial mean weight), with vitamin E deficiency with or without selenium resulted in the following deficiency signs: extreme anemia, pale gills, anisocytosis, poikilocytosis, elevated plasma protein, exudative diathesis, dermal depigmentation, in vitro ascorbic acid-stimulated peroxidation in hepatic microsomes, yellow-orange liver color, yellow-brown intestinal contents, enlarged gall bladder distended with dark green bile, low vitamin E in carcass and hepatic tissue, muscular dystrophy, increased carcass fat and water, and a response to handling characterized by a transitory fainting with interruption in swimming. A deficiency of dietary selenium suppressed plasma glutathione peroxidase activity. Supplemental selenium with vitamin E significantly increased tocopherol activity in hepatic, but not carcass tissues. Supplements of both vitamin E and selenium were necessary to prevent muscular dystrophy.

Selenium Nanoparticles for Stress-Resilient Fish and Livestock.

PubMed

Sarkar, Biplab; Bhattacharjee, Surajit; Daware, Akshay; Tribedi, Prosun; Krishnani, K K; Minhas, P S

2015-12-01

The fisheries and livestock sectors capture the highest share of protein-rich animal food and demonstrate accelerated growth as an agriculture subsidiary. Environmental pollution, climate change, as well as pathogenic invasions exert increasing stress impacts that lead the productivity momentum at a crossroads. Oxidative stress is the most common form of stress phenomenon responsible for the retardation of productivity in fisheries and livestock. Essential micronutrients play a determinant role in combating oxidative stress. Selenium, one of the essential micronutrients, appears as a potent antioxidant with reduced toxicity in its nanoscale form. In the present review, different methods of synthesis and characterization of nanoscale selenium have been discussed. The functional characterization of nano-selenium in terms of its effect on growth patterns, feed digestibility, and reproductive system has been discussed to elucidate the mechanism of action. Moreover, its anti-carcinogenic and antioxidant potentiality, antimicrobial and immunomodulatory efficacy, and fatty acid reduction in liver have been deciphered as the new phenomena of nano-selenium application. Biologically synthesized nano-selenium raises hope for pharmacologically enriched, naturally stable nanoscale selenium with high ecological viability. Hence, nano-selenium can be administered with commercial feeds for improvising stress resilience and productivity of fish and livestock.

Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer

USDA-ARS?s Scientific Manuscript database

Studies were conducted in order to investigate whether there were relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status and race. Initial efforts focused on the SELENOF protein which is cytoplasmic in human prostate cancer cell lines and tumor tissue...

Selenium-mercury relationships in Idaho lake fish versus Northeastern USA lake fish

EPA Science Inventory

Methyl-mercury (MeHg) exposure to wildlife and humans occurs primarily through the foodweb, notably fish consumption. Selenium moderates the toxicity of MeHg in all animal models that utilize selenoenzymatic protein synthesis, as do humans. A Se:Hg molar ratio of <1:1 appears to...

Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication.

PubMed

Mukherjee, Sourav; Weiner, Warren S; Schroeder, Chad E; Simpson, Denise S; Hanson, Alicia M; Sweeney, Noreena L; Marvin, Rachel K; Ndjomou, Jean; Kolli, Rajesh; Isailovic, Dragan; Schoenen, Frank J; Frick, David N

2014-10-17

The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease, which cleaves viral and host proteins, and a helicase that separates nucleic acid strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and compounds in clinical trials, target the NS3 protease, but few helicase inhibitors that function as antivirals have been reported. This study focuses on the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3-one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3 helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind nucleic acids, and to hydrolyze ATP, and about 1 μM ebselen was sufficient to inhibit each of these activities by 50%. However, ebselen had no effect on the activity of the NS3 protease, even at 100 times higher ebselen concentrations. At concentrations below 10 μM, the ability of ebselen to inhibit HCV helicase was reversible, but prolonged incubation of HCV helicase with higher ebselen concentrations led to irreversible inhibition and the formation of covalent adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen analogues with sulfur replacing the selenium were just as potent HCV helicase inhibitors as ebselen, but the length of the linker between the phenyl and benzisoselenazol rings was critical. Modifications of the phenyl ring also affected compound potency over 30-fold, and ebselen was a far more potent helicase inhibitor than other, structurally unrelated, thiol-modifying agents. Ebselen analogues were also more effective antiviral agents, and they were less toxic to hepatocytes than ebselen. Although the above structure-activity relationship studies suggest that ebselen targets a specific site on NS3, we were unable to confirm binding to either the NS3 ATP binding site or nucleic acid binding cleft by examining the effects of ebselen on NS3 proteins lacking key cysteines.

Molecular mechanism of brain impairment caused by drinking-acquired fluorosis and selenium intervention.

PubMed

Zheng, Xiangren; Sun, Yan; Ke, Lulu; Ouyang, Wei; Zhang, Zigui

2016-04-01

This study investigated the molecular mechanism of brain impairment induced by drinking fluoridated water and selenium intervention. Results showed that the learning and memory of rats in NaF group significantly decreased. Moreover, the number of apoptotic cells, the expression levels of Cytc mRNA and protein, and the expression levels of Caspase-9 and Caspase-3 mRNA significantly increased; by contrast, Caspase-9 and Caspase-3 protein levels significantly decreased. Compared with the NaF group, the mRNA levels of Cytc and Caspase-9, as well as the protein levels of Cytc in NaF+Se group, significantly decreased. Conversely, the protein levels of Caspase-3 and Caspase-9, as well as the mRNA levels of Caspase-3, significantly increased. Thus, the mitochondrial CytC-Caspase-9-Caspase-3 apoptosis pathway in the hippocampus was one of the mechanisms leading to fluorosis-induced brain damage. Furthermore, the Cytc signaling molecules were possibly the key target molecules in fluorosis-induced apoptosis, and selenium could alleviate fluorosis-induced brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population.

PubMed

Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik; Debrabant, Birgit; Nybo, Mads; Cold, Søren; Hegedüs, Laszlo

2015-06-01

Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period. Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation. Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved. © 2015 European Society of Endocrinology.

Uptake and speciation of selenium in garlic cultivated in soil amended with symbiotic fungi (mycorrhiza) and selenate.

PubMed

Larsen, Erik H; Lobinski, Ryszard; Burger-Meÿer, Karin; Hansen, Marianne; Ruzik, Rafal; Mazurowska, Lena; Rasmussen, Peter Have; Sloth, Jens J; Scholten, Olga; Kik, Chris

2006-07-01

The scope of the work was to investigate the influence of selenate fertilisation and the addition of symbiotic fungi (mycorrhiza) to soil on selenium and selenium species concentrations in garlic. The selenium species were extracted from garlic cultivated in experimental plots by proteolytic enzymes, which ensured liberation of selenium species contained in peptides or proteins. Separate extractions using an aqueous solution of enzyme-deactivating hydroxylamine hydrochloride counteracted the possible degradation of labile selenium species by enzymes (such as alliinase) that occur naturally in garlic. The selenium content in garlic, which was analysed by ICP-MS, showed that addition of mycorrhiza to the natural soil increased the selenium uptake by garlic tenfold to 15 microg g(-1) (dry mass). Fertilisation with selenate and addition of mycorrhiza strongly increased the selenium content in garlic to around one part per thousand. The parallel analysis of the sample extracts by cation exchange and reversed-phase HPLC with ICP-MS detection showed that gamma-glutamyl-Se-methyl-selenocysteine amounted to 2/3, whereas methylselenocysteine, selenomethionine and selenate each amounted to a few percent of the total chromatographed selenium in all garlic samples. Se-allyl-selenocysteine and Se-propyl-selenocysteine, which are selenium analogues of biologically active sulfur-containing amino acids known to occur in garlic, were searched for but not detected in any of the extracts. The amendment of soil by mycorrhiza and/or by selenate increased the content of selenium but not the distribution of detected selenium species in garlic. Finally, the use of two-dimensional HPLC (size exclusion followed by reversed-phase) allowed the structural characterisation of gamma-glutamyl-Se-methyl-selenocysteine and gamma-glutamyl-Se-methyl-selenomethionine in isolated chromatographic fractions by quadrupole time-of-flight mass spectrometry.

Erythrocyte selenium concentration predicts intensive care unit and hospital mortality in patients with septic shock: a prospective observational study

PubMed Central

2014-01-01

Introduction Selenoenzymes can modulate the extent of oxidative stress, which is recognized as a key feature of septic shock. The pathophysiologic role of erythrocyte selenium concentration in patients with septic shock remains unknown. Therefore, the objective of this study was to evaluate the association of erythrocyte selenium concentration with glutathione peroxidase (GPx1) activity, GPx1 polymorphisms and with ICU and hospital mortality in septic shock patients. Methods This prospective study included all patients older than 18 years with septic shock on admission or during their ICU stay, admitted to one of the three ICUs of our institution, from January to August 2012. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 72 hours of the patients’ admission or within 72 hours of the septic shock diagnosis for determination of selenium status, protein carbonyl concentration, GPx1 activity and GPx1 Pro198Leu polymorphism (rs 1050450) genotyping. Results A total of 110 consecutive patients were evaluated. The mean age was 57.6 ± 15.9 years, 63.6% were male. Regarding selenium status, only erythrocyte selenium concentration was lower in patients who died in the ICU. The frequencies for GPx1 Pro198Leu polymorphism were 55%, 38% and 7% for Pro/Pro, Pro/Leu and Leu/Leu, respectively. In the logistic regression models, erythrocyte selenium concentration was associated with ICU and hospital mortality in patients with septic shock even after adjustment for protein carbonyl concentration and acute physiology and chronic health evaluation II score (APACHE II) or sequential organ failure assessment (SOFA). Conclusions Erythrocyte selenium concentration was a predictor of ICU and hospital mortality in patients with septic shock. However, this effect was not due to GPx1 activity or Pro198Leu polymorphism. PMID:24887198

Selenium compounds activate ATM-dependent DNA damage responses via the mismatch repair protein hMLH1 in colorectal cancer cells

USDA-ARS?s Scientific Manuscript database

Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR) process. Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells ...

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

PubMed Central

Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2014-01-01

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

A gene-environment interaction analysis of plasma selenium with prevalent and incident diabetes: The Hortega study.

PubMed

Galan-Chilet, Inmaculada; Grau-Perez, Maria; De Marco, Griselda; Guallar, Eliseo; Martin-Escudero, Juan Carlos; Dominguez-Lucas, Alejandro; Gonzalez-Manzano, Isabel; Lopez-Izquierdo, Raul; Briongos-Figuero, Laisa Socorro; Redon, Josep; Chaves, Felipe Javier; Tellez-Plaza, Maria

2017-08-01

Selenium and single-nucleotide-polymorphisms in selenoprotein genes have been associated to diabetes. However, the interaction of selenium with genetic variation in diabetes and oxidative stress-related genes has not been evaluated as a potential determinant of diabetes risk. We evaluated the cross-sectional and prospective associations of plasma selenium concentrations with type 2 diabetes, and the interaction of selenium concentrations with genetic variation in candidate polymorphisms, in a representative sample of 1452 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.2µg/L. 120 participants had diabetes at baseline. Among diabetes-free participants who were not lost during the follow-up (N=1234), 75 developed diabetes over time. The multivariable adjusted odds ratios (95% confidence interval) for diabetes prevalence comparing the second and third to the first tertiles of plasma selenium levels were 1.80 (1.03, 3.14) and 1.97 (1.14, 3.41), respectively. The corresponding hazard ratios (95% CI) for diabetes incidence were 1.76 (0.96, 3.22) and 1.80 (0.98, 3.31), respectively. In addition, we observed significant interactions between selenium and polymorphisms in PPARGC1A, and in genes encoding mitochondrial proteins, such as BCS1L and SDHA, and suggestive interactions of selenium with other genes related to selenoproteins and redox metabolism. Plasma selenium was positively associated with prevalent and incident diabetes. While the statistical interactions of selenium with polymorphisms involved in regulation of redox and insulin signaling pathways provide biological plausibility to the positive associations of selenium with diabetes, further research is needed to elucidate the causal pathways underlying these associations. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Increased plasma selenium is associated with better outcomes in children with systemic inflammation.

PubMed

Leite, Heitor Pons; Nogueira, Paulo Cesar Koch; Iglesias, Simone Brasil de Oliveira; de Oliveira, Susyane Vieira; Sarni, Roseli Oselka Saccardo

2015-03-01

The aim of this study was to assess the effects of changes in plasma selenium on the outcome of critically ill children. Plasma selenium was prospectively measured in 99 children with acute systemic inflammation. The exposure variables were selenium level on admission and on day 5 of stay in the intensive care unit (ICU) and the difference in selenium concentrations between day 5 post-admission and the ICU admission (delta selenium). Selenium was given only as part of enteral diets. Age, malnutrition, red cell glutathione peroxidase-1 activity, serum C-reactive protein, Pediatric Index of Mortality 2, and Pediatric Logistic Organ Dysfunction scores were analyzed as covariates. The outcome variables were ventilator-free days, ICU-free days, and 28-d mortality. Plasma selenium concentrations increased from admission (median 23.4 μg/L, interquartile range 12.0-30.8) to day 5 (median 25.1 μg/L, interquartile range 16.0-39.0; P = 0.018). After adjustment for confounding factors, a delta selenium increase of 10 μg/L was associated with reductions in ventilator days (1.3 d; 95% confidence interval [CI], 0.2-2.3; P = 0.017) and ICU days (1.4 d; 95% CI, 0.5-2.3; P < 0.01). Delta selenium >0 was associated with decreased 28-d mortality on a univariate model (odds ratio, 0.67; 95% CI, 0.46-0.97; P = 0.036). The mean daily selenium intake (6.82 μg; range 0-48.66 μg) was correlated with the increase in selenium concentrations on day 5. An increase in plasma selenium is independently associated with shorter times of ventilation and ICU stay in children with systemic inflammation. These findings raise the hypothesis that selenium supplementation could be beneficial in children with critical illnesses. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of nano red elemental selenium on sodium currents in rat dorsal root ganglion neurons.

PubMed

Yuan, Huijun; Lin, Jiarui; Lan, Tonghan

2006-01-01

Nano red elemental selenium (Nano-Se), was demonstrated to be useful in medical and scientific researches. Here, we investigated the effects of Nano-Se on sodium currents on rat dorsal root ganglion neurons (DRG), using the whole-cell patch clamp method. Nano-Se reversibly decrease the I(Na)(TTX-S) in a concentration-dependent, time-dependent and open-channel block manners without affecting I(Na)(TTX-R). It shifted the steady-state activation and inactivation curves for I(Na) to more negative potentials. In the research of recovery from inactivation, the recovery time constant is longer in the present of Nano-Se. Nano-Se had a weaker inhibitory effect on I(Na), compared with marked decrease caused by selenite which indicated that Nano-Se is less neurotoxic than selenite in short-term/large dose treatments and had similar bio availability to sodium selenite. The results of interaction between the effects of Nano-Se and selenite on sodium currents indicated a negative allosteric interaction between the selenite binding site and the Nano-Se binding site or that they have the same competitive binding site.

Downregulation of plasma SELENBP1 protein in patients with recent-onset schizophrenia.

PubMed

Chau, Edith J; Mostaid, Md Shaki; Cropley, Vanessa; McGorry, Patrick; Pantelis, Christos; Bousman, Chad A; Everall, Ian P

2018-07-13

Upregulation of selenium binding protein 1 (SELENBP1) mRNA expression has been reported in schizophrenia, primarily in the dorsolateral prefrontal cortex. However, peripheral blood studies are limited and results are inconsistent. In this study, we examined SELENBP1 mRNA expression in whole blood and protein expression in plasma from patients with recent-onset schizophrenia (n = 30), treatment-resistant schizophrenia (n = 71) and healthy controls (n = 57). We also examined the effects of SELENBP1 genetic variation on gene and protein expression. We found lower SELENBP1 plasma protein levels in patients with recent-onset schizophrenia (p = 0.042) but not in treatment-resistant schizophrenia (p = 0.81). Measurement of peripheral mRNA levels showed no difference between treatment-resistant schizophrenia and healthy controls (p = 0.234) but clozapine plasma levels (p = 0.036) and duration of illness (p = 0.028) were positively correlated with mRNA levels. Genetic variation was not associated with mRNA or protein expression. Our data represent the first peripheral proteomic study of SELENBP1 in schizophrenia and suggest that plasma SELENBP1 protein is downregulated in patients with recent-onset schizophrenia. Copyright © 2018 Elsevier Inc. All rights reserved.

Dietary linseed oil supplemented with organic selenium improved the fatty acid nutritional profile, muscular selenium deposition, water retention, and tenderness of fresh pork.

PubMed

Jiang, Jiang; Tang, Xinyue; Xue, Yan; Lin, Gang; Xiong, Youling L

2017-09-01

Cross-bred pigs were fed a control diet (with 0.3ppm sodium selenite and 1.5% soybean oil) or organic selenium diets (0.3ppm Se-Yeast with 1.5% soybean or linseed oil) to investigate nutrient supplement effects on meat quality and oxidative stability. The organic selenium diets increased muscular selenium content up to 54%, and linseed oil increased n-3 fatty acids two-fold while lowering the n-6/n-3 fatty acid ratio from 13.9 to 5.9 over the selenite control diet (P<0.05). Organic selenium yeast treatments with linseed oil reduced pork drip loss by 58-74% when compared with diets with soybean oil. Lightness of fresh pork was slightly less for organic selenium groups than inorganic (P<0.05), but redness was mostly similar. Lipid oxidation (TBARS) and protein oxidation (sulfhydryl) during meat storage (4°C up to 6days) showed no appreciable difference (P>0.05) between diets, in agreement with the lack of notable difference in endogenous antioxidant enzyme activity between these meat groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Roles of the Interaction of BCL2-Antagonist/Killer 1, Apoptotic Peptidase Activating Factor 1 and Selenium in the Pathogenesis of Kashin-Beck Disease.

PubMed

Wang, Sen; Duan, Chen; Zhang, Feng; Wang, Xi; Guo, Xiong

2016-03-01

BCL2-antagonist/killer 1 (BAK1) and apoptotic peptidase activating factor 1 (APAF1) are significant genes in apoptosis signalling pathway of Kashin-Beck disease (KBD). We aimed to verify the protein expression levels of BAK1 and APAF1 in the cartilage and chondrocytes of patients with KBD. Additionally, we explored the relationship between the levels of these proteins and selenium concentration. Chondrocytes was cultured and treated with sodium selenite in vitro. Immunohistochemistry and Western blotting were used to verify the expression levels of BAK1 and APAF1. Compared with the control samples, APAF1 was upregulated and BAK1 was downregulated in the cartilage and chondrocytes of KBD patients. APAF1 expression was higher in the middle and deep zone in the KBD cartilage. APAF1 levels decreased gradually with the increasing selenium concentration (0.05, 0.10 and 0.25 mg/L). BAK1 expression in the 0.25 mg/L selenium group was lower than that of the control group. Different selenium concentrations had varying effects on BAK1 and APAF1 levels. APAF1 may play an important role in the pathogenesis of KBD. APAF1-related apoptosis was more pronounced in the middle and deep zones of the KBD cartilage. APAF may represent a potentially novel molecular target, which may be a biomarker of the role of selenium on the prevention and treatment of KBD. The role of BAK1 in the pathogenesis of KBD requires further study.

Effect of forms of selenium on the accumulation of selenium, sulfur, and forms of nitrogen and phosphorus in forage cowpea (Vigna sinensis)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, M.; Singh, N.

1979-05-01

The effects of forms of selenium on the accumulation of sulfur, selenium, and forms of nitrogen and phosphorus in cowpea (Vigna sinensis) were studied in pots in the greenhouse at Haryana Agricultural University, Hissar, India. The soil used was sandy, and forms of selenium added were Na/sub 2/SeO/sub 4/ 10H/sub 2/O, Na/sub 2/SeO/sub 3/ 5H/sub 2/O, H/sub 2/SeO/sub 3/, and elemental selenium at the rate of 0, 1, 2.5 and 5 ppM. Dry matter yield and sulfur content decreased with increased selenium application. This inhibition in plants, attributable to applied selenium, was in the order SeO/sub 4/ > H/sub 2/SeO/submore » 3/ > SeO/sub 3/ > elemental selenium. Plant selenium increased with increasing application of all forms of selenium. The highest plant selenium (11.58 ppM) was in the plants treated with SeO/sub 4/, followed by the plants treated with H/sub 2/SeO/sub 3/, SeO/sub 3/, and elemental selenium. The total plant phosphorus increased with increased selenium application in any form, but maximum phosphorus occurred in SeO/sub 3/-treated plants. The inorganic phosphorus increased similarly, the largest amount occurring in SeO/sub 4/-treated plants. Organic phosphorus decreased with selenium application; minimum concentration was recorded in SeO/sub 4/-treated plants. Soluble nitrogen decreased, relative to the control, with applications of 2.5 and 5 ppM selenium. This decrease was minimal for elemental selenium and maximum for SeO/sub 4/. Soluble nitrogen, in the case of SeO/sub 3/ was higher than for H/sub 2/SeO/sub 3/. Total plant nitrogen and protein also decreased. Amino N, amide N, and ammoniacal and nitrate N increased, compared to the control. The largest amount of all these forms was noted in SeO/sub 4/-treated plants. Overall, among the forms of selenium normally reported in soils, the SeO/sub 4/ form showed the highest inhibition, whereas SeO/sub 3/ showed less than both SeO/sub 4/ and H/sub 2/SeO/sub 3/.« less

Role of selenium-containing proteins in T cell and macrophage function

PubMed Central

Carlson, Bradley A.; Yoo, Min-Hyuk; Shrimali, Rajeev K.; Irons, Robert; Gladyshev, Vadim N.; Hatfield, Dolph L.; Park, Jin Mo

2011-01-01

Synopsis Selenium has been known for many years to have a role in boosting immune function, but the manner in which this element acts at the molecular level in host defense and inflammatory diseases is poorly understood. To elucidate the role of selenium-containing proteins in immune function, we knocked out the expression of this protein class in T cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T cells manifested reduced pools of mature and functional T cells in lymphoid tissues and an impairment in T cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T cells led to an inability of these cells to suppress reactive oxygen species (ROS) production, which in turn affected their ability to proliferate in response to T cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in immune function and tissue homeostasis. PMID:20576203

Effects of a treatment with Se-rich rice flour high in resistant starch on enteric dysbiosis and chronic inflammation in diabetic ICR mice.

PubMed

Yuan, Huaibo; Wang, Wenjuan; Chen, Deyi; Zhu, Xiping; Meng, Lina

2017-05-01

Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower. Similar results were also found in NRRS-treated mice. In contrast, no significant difference was found between NR-treated and diabetic control groups. The treatments with SRRS and NRRS reduced the faecal pH values of the diabetic mice. Regarding the inflammatory factor levels, lower levels of serum C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-k-gene binding (NF-κB) and leptin (LEP) and higher adiponutrin (ADPN) levels were found in the SRRS and NRRS-treated mice compared with the diabetic and NR-treated mice. In addition, the CRP, IL-6 and NF-κB levels in the SRRS-treated mice were significantly reduced compared with those observed in the NRRS-treated mice. The reverse transcription-PCR (RT-PCR) results showed that the SRRS and NRRS-treated mice presented higher expression levels of orphan G protein-coupled receptor 41 (GPR41) and orphan G protein-coupled receptor 43 (GPR43) proteins compared with diabetic mice and NR-treated mice. These results indicate that treatments with rice high in RS exert beneficial effects by improving enteric dysbiosis and chronic inflammation. In addition, selenium and RS may exert synergistic effects on chronic inflammation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Multispecies Biofilms Transform Selenium Oxyanions into Elemental Selenium Particles: Studies Using Combined Synchrotron X-ray Fluorescence Imaging and Scanning Transmission X-ray Microscopy.

PubMed

Yang, Soo In; George, Graham N; Lawrence, John R; Kaminskyj, Susan G W; Dynes, James J; Lai, Barry; Pickering, Ingrid J

2016-10-04

Selenium (Se) is an element of growing environmental concern, because low aqueous concentrations can lead to biomagnification through the aquatic food web. Biofilms, naturally occurring microbial consortia, play numerous important roles in the environment, especially in biogeochemical cycling of toxic elements in aquatic systems. The complexity of naturally forming multispecies biofilms presents challenges for characterization because conventional microscopic techniques require chemical and physical modifications of the sample. Here, multispecies biofilms biotransforming selenium oxyanions were characterized using X-ray fluorescence imaging (XFI) and scanning transmission X-ray microscopy (STXM). These complementary synchrotron techniques required minimal sample preparation and were applied correlatively to the same biofilm areas. Sub-micrometer XFI showed distributions of Se and endogenous metals, while Se K-edge X-ray absorption spectroscopy indicated the presence of elemental Se (Se 0 ). Nanoscale carbon K-edge STXM revealed the distributions of microbial cells, extracellular polymeric substances (EPS), and lipids using the protein, saccharide, and lipid signatures, respectively, together with highly localized Se 0 using the Se L III edge. Transmission electron microscopy showed the electron-dense particle diameter to be 50-700 nm, suggesting Se 0 nanoparticles. The intimate association of Se 0 particles with protein and polysaccharide biofilm components has implications for the bioavailability of selenium in the environment.

Multispecies Biofilms Transform Selenium Oxyanions into Elemental Selenium Particles: Studies Using Combined Synchrotron X-ray Fluorescence Imaging and Scanning Transmission X-ray Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Soo In; George, Graham N.; Lawrence, John R.

2016-10-04

Selenium (Se) is an element of growing environmental concern, because low aqueous concentrations can lead to biomagnification through the aquatic food web. Biofilms, naturally occurring microbial consortia, play numerous important roles in the environment, especially in biogeochemical cycling of toxic elements in aquatic systems. The complexity of naturally forming multispecies biofilms presents challenges for characterization because conventional microscopic techniques require chemical and physical modifications of the sample. Here, multispecies biofilms biotransforming selenium oxyanions were characterized using X-ray fluorescence imaging (XFI) and scanning transmission X-ray microscopy (STXM). These complementary synchrotron techniques required minimal sample preparation and were applied correlatively to themore » same biofilm areas. Sub-micrometer XFI showed distributions of Se and endogenous metals, while Se K-edge X-ray absorption spectroscopy indicated the presence of elemental Se (Se0). Nanoscale carbon K-edge STXM revealed the distributions of microbial cells, extracellular polymeric substances (EPS), and lipids using the protein, saccharide, and lipid signatures, respectively, together with highly localized Se0 using the Se LIII edge. Transmission electron microscopy showed the electron-dense particle diameter to be 50–700 nm, suggesting Se0 nanoparticles. The intimate association of Se0 particles with protein and polysaccharide biofilm components has implications for the bioavailability of selenium in the environment.« less

Differential expression profiling of the hepatic proteome in a rat model of dioxin resistance: correlation with genomic and transcriptomic analyses.

PubMed

Pastorelli, Roberta; Carpi, Donatella; Campagna, Roberta; Airoldi, Luisa; Pohjanvirta, Raimo; Viluksela, Matti; Hakansson, Helen; Boutros, Paul C; Moffat, Ivy D; Okey, Allan B; Fanelli, Roberto

2006-05-01

One characteristic feature of acute 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity is dramatic interspecies and interstrain variability in sensitivity. This complicates dioxin risk assessment for humans. However, this variability also provides a means of characterizing mechanisms of dioxin toxicity. Long-Evans (Turku/AB) rats are orders of magnitude more susceptible to TCDD lethality than Han/Wistar (Kuopio) rats, and this difference constitutes a very useful model for identifying mechanisms of dioxin toxicity. We adopted a proteomic approach to identify the differential effects of TCDD exposure on liver protein expression in Han/Wistar rats as compared with Long-Evans rats. This allows determination of which, if any, protein markers are indicative of differences in dioxin susceptibility and/or responsible for conferring resistance. Differential protein expression in total liver protein was assessed using two-dimensional gel electrophoresis, computerized gel image analysis, in-gel digestion, and mass spectrometry. We observed significant changes in the abundance of several proteins, which fall into three general classes: (i) TCDD-independent and exclusively strain-specific (e.g. isoforms of the protein-disulfide isomerase A3, regucalcin, and agmatine ureohydrolase); (ii) strain-independent and only dependent on TCDD exposure (e.g. aldehyde dehydrogenase 3A1 and rat selenium-binding protein 2); (iii) dependent on both TCDD exposure and strain (e.g. oxidative stress-related proteins, apoptosis-inducing factor, and MAWD-binding protein). By integrating transcriptomic (microarray) data and genomic data (computational search of regulatory elements), we found that protein expression levels were mainly controlled at the level of transcription. These results reveal, for the first time, a subset of hepatic proteins that are differentially regulated in response to TCDD in a strain-specific manner. Some of these differential responses may play a role in establishing the major differences in TCDD response between these two strains of rats. As such, our work is expected to lead to new insights into the mechanism of TCDD toxicity and resistance.

Identification of a differentially-expressed gene in fatty liver of overfeeding geese.

PubMed

Zhao, Ayong; Tang, Huachun; Lu, Sufang; He, Ruiguo

2007-09-01

In response to overfeeding, geese develop fatty liver. To understand the fattening mechanism, mRNA differential display reverse transcription PCR was used to study the gene expression differences between French Landes grey geese and Xupu white geese in conditions of overfeeding and normal feeding. One gene was found to be up-regulated in the fatty liver in both breeds, and it has a 1797 bp cDNA with 83% identity to chicken SELENBP1. The sequence analysis revealed that its open reading frame of 1413 bp encodes a protein of 471 amino acids, which contains a putative conserved domain of 56 kDa selenium binding protein with high homology to its homologues of chicken (95%), rat (86%), mouse (84%), human (86%), monkey (86%), dog (86%), and cattle (86%). The function of this protein has been briefly reviewed based on published information. In tissue expression analysis, the expression of geese SELENBP1 mRNA was found to be higher in liver or kidney than in other tested tissues. The results showed that overfeeding could increase the mRNA expression level of geese SELENBP1.

Selenium: Mercury Molar Ratios in Freshwater Fish in the Columbia River Basin: Potential Applications for Specific Fish Consumption Advisories.

PubMed

Cusack, Leanne K; Eagles-Smith, Collin; Harding, Anna K; Kile, Molly; Stone, Dave

2017-07-01

Fish provide a valuable source of beneficial nutrients and are an excellent source of low fat protein. However, fish are also the primary source of methylmercury exposure in humans. Selenium often co-occurs with mercury and there is some evidence that selenium can protect against mercury toxicity yet States issue fish consumption advisories based solely on the risks that methylmercury pose to human health. Recently, it has been suggested the selenium: mercury molar ratio be considered in risk management. In order for agencies to utilize the ratio to set consumption guidelines, it is important to evaluate the variability in selenium and mercury in different fish species. We examined 10 different freshwater fish species found within the Columbia River Basin in order to determine the inter- and intra-specific variability in the selenium: mercury molar ratios and the selenium health benefit values. We found significant variation in selenium: mercury molar ratios. The mean molar ratios for each species were all above 1:1, ranging from 3.42:1 in Walleye to 27.2:1 in Chinook salmon. There was a positive correlation between both mercury and selenium with length for each fish species apart from yellow perch and rainbow trout. All species had health benefit values greater than 2. We observed considerable variability in selenium: mercury molar ratios within fish species collected in the Columbia River Basin. Although incorporating selenium: mercury molar ratios into fish consumption holds the potential for refining advisories and assessing the risk of methylmercury exposure, the current understanding of how these ratios apply is insufficient, and further understanding of drivers of variability in the ratios is needed.

Selenium: Mercury molar ratios in freshwater fish in the Columbia River Basin: Potential applications for specific fish consumption advisories

USGS Publications Warehouse

Cusack, Leanne K.; Eagles-Smith, Collin A.; Harding, Anna K.; Kile, Molly; Stone, Dave

2017-01-01

Fish provide a valuable source of beneficial nutrients and are an excellent source of low fat protein. However, fish are also the primary source of methylmercury exposure in humans. Selenium often co-occurs with mercury and there is some evidence that selenium can protect against mercury toxicity yet States issue fish consumption advisories based solely on the risks that methylmercury pose to human health. Recently, it has been suggested the selenium: mercury molar ratio be considered in risk management. In order for agencies to utilize the ratio to set consumption guidelines, it is important to evaluate the variability in selenium and mercury in different fish species. We examined 10 different freshwater fish species found within the Columbia River Basin in order to determine the inter- and intra-specific variability in the selenium: mercury molar ratios and the selenium health benefit values. We found significant variation in selenium: mercury molar ratios. The mean molar ratios for each species were all above 1:1, ranging from 3.42:1 in Walleye to 27.2:1 in Chinook salmon. There was a positive correlation between both mercury and selenium with length for each fish species apart from yellow perch and rainbow trout. All species had health benefit values greater than 2. We observed considerable variability in selenium: mercury molar ratios within fish species collected in the Columbia River Basin. Although incorporating selenium: mercury molar ratios into fish consumption holds the potential for refining advisories and assessing the risk of methylmercury exposure, the current understanding of how these ratios apply is insufficient, and further understanding of drivers of variability in the ratios is needed.

Interactive effects of arsenate, selenium, and dietary protein on survival, growth, and physiology in mallard ducklings

USGS Publications Warehouse

Hoffman, D.J.; Sanderson, C.J.; LeCaptain, L.J.; Cromartie, E.; Pendleton, G.W.

1992-01-01

High concentrations of arsenic (As) and selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Total biomass of invertebrates, a maJor source of protein for wild ducklings, may vary in environments that are contaminated with selenium. Dayold mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) containing 22% protein or diets containing 15 ppm Se (as selenomethionine), 60 ppm Se, 200 ppm As (as sodium arsenate), 15 ppm Se with 200 ppm As, or 60 ppm Se with 200 ppm As. In a concurrent experiment, the same sequence was repeated with a proteinrestricted (7%) but isocaloric diet. After 4 weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and livers had histopathological lesions. Arsenic alone caused some reduction in growth. Antagonistic interactive effects occurred between As and Se, including complete to partial alleviation of the following Se effects: mortality, impaired growth, hepatic lesions and lipid peroxidation, and altered glutathione and thiol status. With 7% protein, survival and growth of controls was less than that with 22% protein, Se (60 ppm) caused 100% mortality, and As (200 ppm) caused mortality, decreased growth, and liver histopathology. These findings suggest the potential for antagonistic effects of Se and As on duckling survival, growth, and physiology with adequate dietary protein but more severe toxicological effects when dietary protein is diminished.

Selenium supplementation to chronic kidney disease patients on hemodialysis does not induce the synthesis of plasma glutathione peroxidase.

PubMed

Zachara, Bronislaw A; Gromadzinska, Jolanta; Zbrog, Zbigniew; Swiech, Rafal; Wasowicz, Wojciech; Twardowska, Ewa; Jablonska, Ewa; Sobala, Wojciech

2009-01-01

Numerous authors have shown that selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in plasma of chronic kidney disease (CKD) patients are lower than in healthy subjects, but there are only few publications on the level of GSH-Px protein in those patients and no reports on the effect of Se supplementation to HD patients on the level of this enzyme. Se concentration and GSH-Px protein level in plasma were measured in a group of 30 CKD patients on hemodialysis (HD) supplemented with 200 microg Se/day for 3 months, and 28 patients on HD administered with placebo. Se concentration was measured by graphite furnace atomic absorption spectrometry and plasma GSH-Px protein level by the sandwich ELISA method using polyclonal antibody specific for human plasma GSH-Px. Se concentration in patients on placebo did not change throughout the 3-month study period, but increased significantly in Se supplemented group. Se supplementation to CKD patients on HD had no effect on the level of GSH-Px protein. The lack of GSH-Px protein in CKD patients on HD is not linked to Se deficiency since the level of this element increased after Se supplementation while enzyme protein level did not change. The damaged kidney of HD patients is unable to synthesize GSH-Px, even after induction with selenium.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

PubMed

Jablonska, Ewa; Reszka, Edyta; Gromadzinska, Jolanta; Wieczorek, Edyta; Krol, Magdalena B; Raimondi, Sara; Socha, Katarzyna; Borawska, Maria H; Wasowicz, Wojciech

2016-12-13

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR , ADIPOR1 , LDHA , PDHA , PDHB , MYC , and HIF1AN . These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Selenium toxicosis in wild aquatic birds

USGS Publications Warehouse

Ohlendorf, H.M.; Kilness, A.W.; Simmons, J.L.; Stroud, R.K.; Hoffman, D.J.; Moore, John F.

1988-01-01

Severe gross and microscopic lesions and other changes were found in adult aquatic birds and in embryos from Kesterson Reservoir (a portion of Kesterson National Wildlife Refuge), Merced County, Calif., during 1984. Adult birds from that area were emaciated, had subacute to extensive chronic hepatic lesions, and had excess fluid and fibrin in the peritoneal cavity. Biochemical changes in their livers included elevated glycogen and non-protein-bound sulfhydryl concentrations and glutathione peroxidase activity but lowered protein, total sulfhydryl, and protein-bound sulfhydryl concentrations. Congenital malformations observed grossly in embryos were often multiple and included anophthalmia, microphthalmia, abnormal beaks, amelia, micromelia, ectrodactyly, and hydrocephaly. Mean concentrations of selenium in livers (94.4 ppm, dry weight) and kidneys (96.6 ppm) of birds collected at the Kesterson ponds were about 10 times those found at a nearby control area (8.3 and 12.2 ppm). We conclude that selenium present in the agricultural drainage water supplied to the Kesterson ponds accumulated in the food chain of aquatic birds to toxic concentrations and caused the lesion and other changes observed.

Hydrolysis of proteins with methanesulfonic acid for improved HPLC-ICP-MS determination of seleno-methionine in yeast and nuts.

PubMed

Wrobel, Katarzyna; Kannamkumarath, Sasi S; Wrobel, Kazimierz; Caruso, Joseph A

2003-01-01

In this work, the use of methanesulfonic acid for protein hydrolysis is proposed for evaluation of Se-methionine in yeast, Brazil nuts, and possibly other selenium-rich biological samples. The hydrolysis was carried out by heating the sample with 4 mol L(-1) acid at reflux for 8 h. Two chromatographic techniques (size-exclusion and ion-pairing) coupled with ICP-MS detection were used to compare the release of Se-methionine from proteins by enzymatic (proteinase K, protease XIV) and acid hydrolyses. A more efficient liberation of Se-methionine was observed by acid hydrolysis. For quantification, the sample extracts were introduced onto a C8 Alltima column, and the separation was achieved with a mobile phase containing 5 mmol L(-1) hexanesulfonic acid in citrate buffer (pH 4.5)/methanol (95:5). The results obtained by standard addition showed 816+/-17 micro g g(-1) and 36.2+/-1.5 micro g g(-1) of selenium in the form of Se-methionine in yeast and nuts, respectively (65% and 75% of total selenium).

Interactive effects of boron, selenium, and dietary protein on survival, growth and physiology in mallard ducklings

USGS Publications Warehouse

Hoffman, D.J.; Sanderson, C.J.; LeCaptain, L.J.; Cromartie, E.; Pendleton, G.W.

1991-01-01

High concentrations of boron (B) and selenium (Se) have been found in aquatic food chains associated with irrigation drainwater. Total biomass of invertebrates, a maJor source of protein for wild ducklings, is sometimes diminished in agricultural drainwater ponds contaminated with Se and B. Dayold mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) containing 22% protein or diets containing 15 ppm (microgram/g) Se (as selenomethionine), 60 ppm Se, 1,000 ppm B (as boric acid), 15 ppm Se with 1,000 ppm B, or 60 ppm Se with 1,000 ppm B. In a concurrent experiment, the above sequence was repeated with a proteinrestricted (7%) but isocaloric diet. After four weeks, blood and tissue samples were collected for biochemical and histological examination. With 22% protein and 60 ppm Se in the diet, duckling survival and growth was reduced and histopathological lesions of the liver occurred. Boron alone caused some reduction in growth. Several interactive effects occurred between B and Se, including further reduction in growth, and increases in plasma glutathione reductase activity, hematocrit, hemoglobin and plasma protein concentrations. With 7% protein, the growth of controls was less than that with 22% protein, 60 ppm Se caused 100% mortality, and growth effects of 15 ppm Se and 1,000 ppm B alone were more pronounced than with 22% protein. Selenium accumulation increased in the liver with 7% protein. Interactive effects were greater for Se and B with 7% protein than with 22% protein and included significant mortality and enhanced accumulation of Se in the liver. These findings suggest the potential for more severe toxicological effects of Se and B independently and interactively on duckling survival and development when dietary protein is diminished.

Biomarkers of Selenium Action in Prostate Cancer

DTIC Science & Technology

2006-03-01

without BPH) transition zone tissue of a 42-year-old man ac- cording to previously described methods [4]. The pre- sence of contaminating epithelial...protein secreted by cells using a sensitive ELISA method . Replicating the conditions used for the microarray analyses, cells were fed fresh medium...4 Introduction Biomarkers of selenium actions in prostate tissue would be of great value in stratifying patients

A global survey of effects of genotype and environment on selenium concentration in lentils (Lens culinaris L.): Implications for nutritional fortification strategies

USDA-ARS?s Scientific Manuscript database

Lentils (Lens culinaris L.) are an important protein and carbohydrate food, rich in essential dietary components and trace elements. Selenium (Se) is an essential micronutrient for human health. For adults, 55 µg of daily Se intake is recommended for better health and cancer prevention. Millions of ...

Chemical characterisation and speciation of organic selenium in cultivated selenium-enriched Agaricus bisporus.

PubMed

Maseko, Tebo; Callahan, Damien L; Dunshea, Frank R; Doronila, Augustine; Kolev, Spas D; Ng, Ken

2013-12-15

The selenium concentration in Agaricus bisporus cultivated in growth compost irrigated with sodium selenite solution increased by 28- and 43-fold compared to the control mushroom irrigated solely with water. Selenium contents of mushroom proteins increased from 13.8 to 60.1 and 14.1 to 137 μgSe/g in caps and stalks from control and selenised mushrooms, respectively. Selenocystine (SeCys; detected as [SeCys]2 dimer), selenomethionine (SeMet), and methyl-selenocysteine (MeSeCys) were separated, identified and quantified by liquid chromatography-electrospray ionisation-mass spectrometry from water solubilised and acetone precipitated proteins, and significant increases were observed for the selenised mushrooms. The maximum selenoamino acids concentration in caps and stalks of control/selenised mushrooms was 4.16/9.65 μg/g dried weight (DW) for SeCys, 0.08/0.58 μg/g DW for SeMet, and 0.031/0.10 μg/g DW for MeSeCys, respectively. The most notable result was the much higher levels of SeCys accumulated by A. bisporus compared to SeMet and MeSeCys, for both control and selenised A. bisporus. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Selenium supplementation in pediatric patients using parenteral nutrition: Is it time to do something?

PubMed

Freitas, Renata Germano Borges de Oliveira Nascimento; Nogueira, Roberto José Negrão; Hessel, Gabriel

2018-03-01

To analyze the nutritional status of selenium and verify the effect of its supplementation in pediatric patients during 14 days of parenteral nutrition (PN). This is a series of cases with patients followed for two weeks while using PN. Data collection was performed at the beginning (T0), in the 7th (T1) and 14th days of PN (T2). The supplemented group received 2 µg/kg/day of selenous acid. Weight and height were measured for nutritional status assessment. Tests requested: plasma selenium, albumin, pre-albumin, C-reactive protein (CRP), total cholesterol and HDL-cholesterol. Fourteen (14) patients with inflammatory process and with low or very low weight for their ages were evaluated. In both groups (with and without supplementation), all patients had low selenium levels. Median plasma selenium concentrations were 17.4 µg/L (T0), 23.0 µg/L (T1) and 20.7 µg/L (T2). Increase and reduction of selenium occurred both in patients with high CRP and in those presenting normalization of this parameter. Lower plasma selenium levels have been detected since the start of the research and supplementation (2 µg/kg/day of selenous acid) was not to enough to approach the reference values.

Restoring effect of selenium on the molecular content, structure and fluidity of diabetic rat kidney brush border cell membrane.

PubMed

Gurbanov, Rafig; Bilgin, Mehmet; Severcan, Feride

2016-04-01

Diabetic kidney disease (DKD) is a dominant factor standing for kidney impairments during diabetes. In this study, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to disclose the diabetes-induced structural changes in the kidney and evaluate the effects of selenium on diabetes. The increase in the area of the olefinic band indicated increased amount of lipid peroxidation end products in diabetic kidney brush border cell membrane. Moreover, saturated lipid content of this cell membrane considerably diminished. DKD was found to disrupt lipid order and cause a decrease in membrane dynamics. However, the administration of selenium at low and medium doses was shown to improve these conditions by changing the lipid contents toward control values, restoring the ordered structure of the lipids and membrane dynamics. Curve-fitting and artificial neural network (ANN) analyses of secondary structures of proteins demonstrated a relative increase in α-helix and reduction in the β-sheet during diabetes in comparison to the control group, which were ameliorated following selenium treatment at low and medium doses. These findings were further confirmed by applying hierarchical cluster analysis (HCA) and principal component analysis (PCA). A clear separation of the experimental groups was obtained with high heterogeneity in the lipid and protein regions. These chemometric analyses showed that the low and medium doses of selenium-treated diabetic groups are successfully segregated from the diabetic group and clustered closer to the control. The study suggests that medium and, more predominantly, low-dose selenium treatment can be efficient in eliminating diabetes-induced structural alterations. Copyright © 2016 Elsevier B.V. All rights reserved

Effects of Selenium-Enriched Probiotics on Lipid Metabolism, Antioxidative Status, Histopathological Lesions, and Related Gene Expression in Mice Fed a High-Fat Diet.

PubMed

Nido, Sonia Agostinho; Shituleni, Shituleni Andreas; Mengistu, Berhe Mekonnen; Liu, Yunhuan; Khan, Alam Zeb; Gan, Fang; Kumbhar, Shahnawaz; Huang, Kehe

2016-06-01

A total of 80 female albino mice were randomly allotted into five groups (n = 16) as follows: (A) normal control, (B) high-fat diet (HFD),; (C) HFD + probiotics (P), (D) HFD + sodium selenite (SS), and (E) HFD + selenium-enriched probiotics (SP). The selenium content of diets in groups A, B, C, D, and E was 0.05, 0.05, 0.05, 0.3, and 0.3 μg/g, respectively. The amount of probiotics contained in groups C and E was similar (Lactobacillus acidophilus 0.25 × 10(11)/mL and Saccharomyces cerevisiae 0.25 × 10(9)/mL colony-forming units (CFU)). The high-fat diet was composed of 15 % lard, 1 % cholesterol, 0.3 % cholic acid, and 83.7 % basal diet. At the end of the 4-week experiment, blood and liver samples were collected for the measurements of lipid metabolism, antioxidative status, histopathological lesions, and related gene expressions. The result shows that HFD significantly increased the body weights and liver damages compared to control, while P, SS, or SP supplementation attenuated the body weights and liver damages in mice. P, SS, or SP supplementation also significantly reversed the changes of alanine aminotransferase (AST), aspartate aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), total protein (TP), high-density lipoprotein (HDL), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalasa (CAT), and malondialdehyde (MDA) levels induced by HFD. Generally, adding P, SS, or SP up-regulated mRNA expression of carnitine palmitoyltransferase-I (CPT1), carnitine palmitoyltransferase II (CPT2), acetyl-CoA acetyltransferase II (ACAT2), acyl-coenzyme A oxidase (ACOX2), and peroxisome proliferator-activated receptor alpha (PPARα) and down-regulated mRNA expression of fatty acid synthase (FAS), lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1 (SREBP1) involved in lipid metabolism. Among the group, adding SP has a maximum effect in improving lipid metabolism, antioxidative status, histopathological lesions, and related gene expression in mice fed a HFD.

Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells via modulating autophagy/apoptosis.

PubMed

Rahman, Md Mostafizur; Uson-Lopez, Rachael A; Sikder, Md Tajuddin; Tan, Gongxun; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki

2018-04-01

Arsenic is well known toxicant responsible for human diseases including cancers. On the other hand, selenium is an essential trace element with significant chemopreventive effects, anticancer potentials and antioxidant properties. Although previous studies have reported antagonism/synergism between arsenic and selenium in biological systems, the biomolecular mechanism/s is still inconclusive. Therefore, to elucidate the molecular phenomena in cellular level, we hypothesized that co-exposure of selenium with arsenic may have suppressive effects on arsenic-induced cytotoxicity. We found that selenium in co-exposure with arsenic increases cell viability, and suppresses oxidative stress induced by arsenic in PC12 cells. Consequently, DNA fragmentation due to arsenic exposure was also reduced by arsenic and selenium co-exposure. Furthermore, western blot analyses revealed that simultaneous exposure of both metals significantly inhibited autophagy which further suppressed apoptosis through positively regulation of key proteins; p-mTOR, p-Akt, p-Foxo1A, p62, and expression of ubiquitin, Bax, Bcl2, NFкB, and caspases 3 and 9, although those are negatively regulated by arsenic. In addition, reverse transcriptase PCR analysis confirmed the involvement of caspase cascade in cell death process induced by arsenic and subsequent inhibition by co-exposure of selenium with arsenic. The cellular accumulation study of arsenic in presence/absence of selenium via inductively coupled plasma mass spectrometry confirmed that selenium effectively retarded the uptake of arsenic in PC12 cells. Finally, these findings imply that selenium is capable to modulate arsenic-induced intrinsic apoptosis pathway via enhancement of mTOR/Akt autophagy signaling pathway through employing antioxidant potentials and through inhibiting the cellular accumulation of arsenic in PC12 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Hughes, David J; Duarte-Salles, Talita; Hybsier, Sandra; Trichopoulou, Antonia; Stepien, Magdalena; Aleksandrova, Krasimira; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Affret, Aurélie; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verena; Kaaks, Rudolf; Boeing, Heiner; Bamia, Christina; Lagiou, Pagona; Peppa, Eleni; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, Hendrik Bastiaan; Peeters, Petra H; Engeset, Dagrun; Weiderpass, Elisabete; Lasheras, Cristina; Agudo, Antonio; Sánchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Hemmingsson, Oskar; Wareham, Nicholas J; Khaw, Kay-Tee; Bradbury, Kathryn E; Cross, Amanda J; Gunter, Marc; Riboli, Elio; Romieu, Isabelle; Schomburg, Lutz; Jenab, Mazda

2016-08-01

Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-μg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. © 2016 American Society for Nutrition.

A Novel Organic Selenium Compound Exerts Unique Regulation of Selenium Speciation, Selenogenome, and Selenoproteins in Broiler Chicks.

PubMed

Zhao, Ling; Sun, Lv-Hui; Huang, Jia-Qiang; Briens, Mickael; Qi, De-Sheng; Xu, Shi-Wen; Lei, Xin Gen

2017-05-01

Background: A new organic selenium compound, 2-hydroxy-4-methylselenobutanoic acid (SeO), displayed a greater bioavailability than sodium selenite (SeNa) or seleno-yeast (SeY) in several species. Objective: This study sought to determine the regulation of the speciation of selenium, expression of selenogenome and selenocysteine biosynthesis and degradation-related genes, and production of selenoproteins by the 3 forms of selenium in the tissues of broiler chicks. Methods: Day-old male chicks ( n = 6 cages/diet, 6 chicks/cage) were fed a selenium-deficient, corn and soy-based diet [base diet (BD), 0.05 mg Se/kg] or the BD + SeNa, SeY, or SeO at 0.2 mg Se/kg for 6 wk. Plasma, livers, and pectoral and thigh muscles were collected at weeks 3 and 6 to assay for total selenium, selenomethionine, selenocysteine, redox status, and selected genes, proteins, and enzymes. Results: Although both SeY and SeO produced greater concentrations ( P < 0.05) of total selenium (20-172%) and of selenomethionine (≤15-fold) in the liver, pectoral muscle, and thigh than those of SeNa, SeO further raised ( P < 0.05) these concentrations by 13-37% and 43-87%, respectively, compared with SeY. Compared with the BD, only SeO enhanced ( P < 0.05) the mRNA of selenoprotein ( Seleno ) s and methionine sulfoxide reductase B1 ( Msrb1 ) in the liver and thigh (62-98%) and thioredoxin reductase (TXRND) activity in the pectoral and thigh muscles (20-37%) at week 3. Furthermore, SeO increased ( P < 0.05) the expression of glutathione peroxidase ( Gpx ) 3 , GPX4, SELENOP, and SELENOU relative to the SeNa group by 26-207%, and the expression of Selenop, O-phosphoseryl-transfer RNA (tRNA):selenocysteinyl-tRNA synthase , GPX4, and SELENOP relative to the SeY group by 23-55% in various tissues. Conclusions: Compared with SeNa or SeY, SeO demonstrated a unique ability to enrich selenomethionine and total selenium depositions, to induce the early expression of Selenos and Mrsb1 mRNA and TXRND activity, and to enhance the protein production of GPX4, SELENOP, and SELENOU in the tissues of chicks. © 2017 American Society for Nutrition.

RNA adducts with Na 2SeO 4 and Na 2SeO 3 - Stability and structural features

NASA Astrophysics Data System (ADS)

Nafisi, Shohreh; Manouchehri, Firouzeh; Montazeri, Maryam

2011-12-01

Selenium compounds are widely available in dietary supplements and have been extensively studied for their antioxidant and anticancer properties. Low blood Se levels were found to be associated with an increased incidence and mortality from various types of cancers. Although many in vivo and clinical trials have been conducted using these compounds, their biochemical and chemical mechanisms of efficacy are the focus of much current research. This study was designed to examine the interaction of Na 2SeO 4 and Na 2SeO 3 with RNA in aqueous solution at physiological conditions, using a constant RNA concentration (6.25 mM) and various sodium selenate and sodium selenite/polynucleotide (phosphate) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared, UV-Visible spectroscopic methods were used to determine the drug binding modes, the binding constants, and the stability of Na 2SeO 4 and Na 2SeO 3-RNA complexes in aqueous solution. Spectroscopic evidence showed that Na 2SeO 4 and Na 2SeO 3 bind to the major and minor grooves of RNA ( via G, A and U bases) with some degree of the Se-phosphate (PO 2) interaction for both compounds with overall binding constants of K(Na 2SeO 4-RNA) = 8.34 × 10 3 and K(Na 2SeO 3-RNA) = 4.57 × 10 3 M -1. The order of selenium salts-biopolymer stability was Na 2SeO 4-RNA > Na 2SeO 3-RNA. RNA aggregations occurred at higher selenium concentrations. No biopolymer conformational changes were observed upon Na 2SeO 4 and Na 2SeO 3 interactions, while RNA remains in the A-family structure.

Selenium-Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer.

PubMed

Yu-Rice, Yi; Edassery, Seby L; Urban, Nicole; Hellstrom, Ingegerd; Hellstrom, Karl Erik; Deng, Youping; Li, Yan; Luborsky, Judith L

2017-03-01

Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to selenium-binding protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n = 41), infertility (n = 92) and control (n = 87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1-positive sera was higher in POF (P = 0.02), irregular ovulation (P = 0.001), unexplained causes (P = 0.02), late (III-IV)-stage OvCa (P = 0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I-II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (P = 0.04) but not non-serous (P = 0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-TP53, markers often studied in OvCa. Anti-TP53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls or when combined with anti-TP53 and CA125, to identify OvCa was evaluated by comparing the area under the curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC = 0.7; P = 0.001) or OvCa (AUC = 0.67; P = 0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-TP53 and anti-SBP1 (AUC = 0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with the development of serous OvCa. © 2017 Society for Reproduction and Fertility.

Selenium-containing allophycocyanin purified from selenium-enriched Spirulina platensis attenuates AAPH-induced oxidative stress in human erythrocytes through inhibition of ROS generation.

PubMed

Zhang, Haobin; Chen, Tianfeng; Jiang, Jie; Wong, Yum-Shing; Yang, Fang; Zheng, Wenjie

2011-08-24

Both selenium and allophycocyanin (APC) have been reported to show novel antioxidant activities. In this study, a fast protein liquid chromatographic method for purification of selenium-containing allophycocyanin (Se-APC) from selenium-enriched Spirulina platensis and the protective effect of Se-APC on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress have been described. After fractionation by ammonium sulfate precipitation, and separation by DEAE-Sepharose ion-exchange and Sephacryl S-300 size exclusion chromatography, Se-APC with purity ratio (A652/A280) of 5.30 and Se concentration of 343.02 μg g(-1) protein was obtained. Se-APC exhibited stronger antioxidant activity than APC by scavenging ABTS (2,2'-azinobis-3-ethylbenzothiazolin-6-sulfonic acid) and AAPH free radicals. The oxidative hemolysis and morphological changes induced by AAPH in human erythrocytes were effectively reversed by coincubation with Se-APC. Lipid oxidation induced by the pro-oxidant agent cupric chloride in human plasma, as evaluated by formation of conjugated diene, was blocked by Se-APC. The accumulation of malondialdehyde, loss of reduced glutathione, and increase in enzyme activities of glutathione peroxidase and reductase induced by AAPH in human erythrocytes were effectively suppressed by Se-APC. Furthermore, Se-APC significantly prevented AAPH-induced intracellular reactive oxygen species (ROS) generation. Taken together, our results suggest that Se-APC demonstrates application potential in treatment of diseases in which excess production of ROS acts as a casual or contributory factor.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 1. Hematological and population level assessment.

PubMed

Lohner, T W; Reash, R J; Willet, V E; Rose, L A

2001-11-01

Sunfish were collected from coal ash effluent-receiving streams and Ohio River watershed reference sites to assess the effects of exposure to low-level selenium concentrations. Selenium, copper, and arsenic concentrations were statistically higher in tissue samples from exposed fish than in reference fish. Leukopenia, lymphocytosis, and neutropenia were evident in exposed fish and were indicative of metal exposure and effect. White blood cell counts and percent lymphocyte values were significantly correlated with liver selenium concentrations. Plasma protein levels were significantly lower in exposed fish than in fish from the Ohio River, indicating that exposed fish may have been nutritionally stressed. Condition factors for fish from the ash pond-receiving streams were the same as, or lower than, those of fish from the reference sites. There was no evidence that the growth rate of fish in the receiving streams differed from that of fish in the reference streams. Despite liver selenium concentrations which exceeded reported toxicity thresholds and evidence of significant hematological changes, there were no significant differences in fish condition factors, liver-somatic indices, or length-weight regressions related to selenium.

[Studies of immunomodulation caused by selenium-enriched phycocyanin].

PubMed

Egorova, E A; Gmoshinskiĭ, I V; Zorin, S N; Mazo, V K

2006-01-01

An influense was studied in rats of selenium enriched phycocyanin (Se-PC) from food microalgae Spirulina on anaphylactic reaction severity and circulating antibody response against model allergen--hen's egg white ovalbumin. Se-PC was introduced into diet in form of protein isolate precipitated with ammonia sulphate. Se-PC dosage made up to 450 mcg per rat daily that corresponded to 5 mcg of selenium. There were no differences revealed between experimental and control group that received standard diet in severity of anaphylactic reaction. Nevertheless rats receiving Se-PC demonstrated significantly increased specific IgG response. The probable immunomodulating properties of Se-PC included into food are discussed.

A novel one-pot green synthesis of selenium nanoparticles and evaluation of its toxicity in zebrafish embryos.

PubMed

Kalishwaralal, Kalimuthu; Jeyabharathi, Subhaschandrabose; Sundar, Krishnan; Muthukumaran, Azhaguchamy

2016-01-01

Over the last 50 years, compelling evidence has accumulated on the beneficial role of selenium in human health. In the present study, different proteins were evaluated as reducing agents for the eco-friendly synthesis of selenium nanoparticles from an aqueous solution of sodium selenite. This method is a simple, low cost green synthesis alternative to chemical synthesis. The high conversion of selenium ions to selenium nanoparticles (SeNPs) was achieved by a reaction mixture of 0.1 g bovine serum albumin and 0.1 g sodium selenite at a reaction temperature of 121°C for 20 min duration. The selenium nanoparticles were characterized by fourier transform infrared (FTIR), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. The FTIR spectral bands were sharp with strong absorption peaks at 1649 and 1551 cm(-1). SEM analysis of the synthesized selenium nanoparticles clearly showed the spherical shape with an average size ranging from 500 to 600 nm. The toxicity of SeNPs was evaluated using zebrafish embryos as a model system. SeNPs induced malformations in zebrafish embryos in a concentration-dependent manner. Selenium nanoparticles at 15-25 μg/ml concentration caused pericardial edema, tail malformation and decrease in heart rate in zebrafish embryos. Treatments with lower concentrations did not alter the heart rate or display any heart abnormalities. This study underlines the importance of identifying optimal SeNP concentration that could have potential therapeutic applications.

Selenium biochemistry and its role for human health.

PubMed

Roman, Marco; Jitaru, Petru; Barbante, Carlo

2014-01-01

Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

Sodium selenite/selenium nanoparticles (SeNPs) protect cardiomyoblasts and zebrafish embryos against ethanol induced oxidative stress.

PubMed

Kalishwaralal, Kalimuthu; Jeyabharathi, Subhaschandrabose; Sundar, Krishnan; Muthukumaran, Azhaguchamy

2015-10-01

Alcoholic cardiomyopathy is the damage caused to the heart muscles due to high level of alcohol consumption resulting in enlargement and inflammation of the heart. Selenium is an important trace element that is beneficial to human health. Selenium protects the cells by preventing the formation of free radicals in the body. In the present study, protein mediated synthesis of SeNPs was investigated. Two different sizes of SeNPs were synthesized using BSA and keratin. The synthesized SeNPs were characterized by scanning electron microscopy (SEM) with elemental composition analysis Energy Dispersive X-ray spectroscopy(EDX) and X-ray diffraction (XRD). This study demonstrates the in vitro and in vivo antioxidative effects of sodium selenite and SeNPs. Further selenium and SeNPs were evaluated for their ability to protect against 1% ethanol induced oxidative stress in H9C2 cell line. The selenium and SeNPs were found to reduce the 1% ethanol-induced oxidative damage through scavenging intracellular reactive oxygen species. The selenium and SeNPs could also prevent pericardial edema induced ethanol treatment and reduced apoptosis and cell death in zebrafish embryos. The results indicate that selenium and SeNPs could potentially be used as an additive in alcoholic beverage industry to control the cardiomyopathy. Copyright © 2015 Elsevier GmbH. All rights reserved.

A bacterial process for selenium nanosphere assembly

PubMed Central

Debieux, Charles M.; Dridge, Elizabeth J.; Mueller, Claudia M.; Splatt, Peter; Paszkiewicz, Konrad; Knight, Iona; Florance, Hannah; Love, John; Titball, Richard W.; Lewis, Richard J.; Richardson, David J.; Butler, Clive S.

2011-01-01

During selenate respiration by Thauera selenatis, the reduction of selenate results in the formation of intracellular selenium (Se) deposits that are ultimately secreted as Se nanospheres of approximately 150 nm in diameter. We report that the Se nanospheres are associated with a protein of approximately 95 kDa. Subsequent experiments to investigate the expression and secretion profile of this protein have demonstrated that it is up-regulated and secreted in response to increasing selenite concentrations. The protein was purified from Se nanospheres, and peptide fragments from a tryptic digest were used to identify the gene in the draft T. selenatis genome. A matched open reading frame was located, encoding a protein with a calculated mass of 94.5 kDa. N-terminal sequence analysis of the mature protein revealed no cleavable signal peptide, suggesting that the protein is exported directly from the cytoplasm. The protein has been called Se factor A (SefA), and homologues of known function have not been reported previously. The sefA gene was cloned and expressed in Escherichia coli, and the recombinant His-tagged SefA purified. In vivo experiments demonstrate that SefA forms larger (approximately 300 nm) Se nanospheres in E. coli when treated with selenite, and these are retained within the cell. In vitro assays demonstrate that the formation of Se nanospheres upon the reduction of selenite by glutathione are stabilized by the presence of SefA. The role of SefA in selenium nanosphere assembly has potential for exploitation in bionanomaterial fabrication. PMID:21808043

The interactive effects of mercury and selenium on metabolic profiles, gene expression and antioxidant enzymes in halophyte Suaeda salsa.

PubMed

Liu, Xiaoli; Lai, Yongkai; Sun, Hushan; Wang, Yiyan; Zou, Ning

2016-04-01

Suaeda salsa is the pioneer halophyte in the Yellow River Delta and was consumed as a popular vegetable. Mercury has become a highly risky contaminant in the sediment of intertidal zones of the Yellow River Delta. In this work, we investigated the interactive effects of mercury and selenium in S. salsa on the basis of metabolic profiling, antioxidant enzyme activities and gene expression quantification. Our results showed that mercury exposure (20 μg L(-1)) inhibited plant growth of S. salsa and induced significant metabolic responses and altered expression levels of INPS, CMO, and MDH in S. salsa samples, together with the increased activities of antioxidant enzymes including SOD and POD. Overall, these results indicated osmotic and oxidative stresses, disturbed protein degradation and energy metabolism change in S. salsa after mercury exposures. Additionally, the addition of selenium could induce both antagonistic and synergistic effects including alleviating protein degradation and aggravating osmotic stress caused by mercury. © 2014 Wiley Periodicals, Inc.

Selenium modification of β-lactoglobulin (β-Lg) and its biological activity.

PubMed

Zheng, GuoQiang; Liu, HaoYu; Zhu, ZhenYuan; Zheng, Jie; Liu, AnJun

2016-08-01

β-Lg is a major whey protein in cow's milk. This study was aimed to find a new kind of organic selenium compound synthesized with β-Lg and selenium dioxide as raw materials under the conditions of vacuum and low temperature. Fourier transformed infrared spectroscopy revealed that seleno-β-lactoglobulin (Se-β-Lg) displayed a strong band at 878cm(-1), belonging to SeO. Circular dichroism spectra results indicated that the conformation of Se-β-Lg was transformed and α-helical, and unordered structures were increased by 9% and 11.2%, respectively, while β-sheet and β-turn were reduced by 14.2% and 6%, respectively. Electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry results showed that there were two protein bands (1-Seβ-Lg and 2-Seβ-Lg) in Se-β-Lg, only one β-Lg connected with selenate in 1-Seβ-Lg, but two β-Lgs, connected to each other, and with selenate, in 2-Seβ-Lg. Morphological observation and hematoxylin and eosin staining indicated that Se-β-lg could induce K562 cell apoptosis. These results indicated that Se-β-Lg could be synthesized by selenium conjugating β-Lg and it had antitumor activity. Copyright © 2016. Published by Elsevier Ltd.

Extracellular thiol-assisted selenium uptake dependent on the xc− cystine transporter explains the cancer-specific cytotoxicity of selenite

PubMed Central

Olm, Eric; Fernandes, Aristi P.; Hebert, Christina; Rundlöf, Anna-Klara; Larsen, Erik H.; Danielsson, Olof; Björnstedt, Mikael

2009-01-01

The selenium salt selenite (SeO32−) is cytotoxic in low to moderate concentrations, with a remarkable specificity for cancer cells resistant to conventional chemotherapy. Our data show that selenium uptake and accumulation, rather than intracellular events, are crucial to the specific selenite cytotoxicity observed in resistant cancer cells. We show that selenium uptake depends on extracellular reduction, and that the extracellular environment is a key factor specific to selenite cytotoxicity. The extracellular reduction is mediated by cysteine, and the efficacy is determined by the uptake of cystine by the xc− antiporter and secretion of cysteine by multidrug resistance proteins, both of which are frequently overexpressed by resistant cancer cells. This mechanism provides molecular evidence for the existence of an inverse relationship between resistance to conventional chemotherapy and sensitivity to selenite cytotoxicity, and highlights the great therapeutic potential in treating multidrug-resistant cancer. PMID:19549867

Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry.

PubMed

Taylor, Ethan Will; Ruzicka, Jan A; Premadasa, Lakmini; Zhao, Lijun

2016-01-01

Regulation of protein expression by non-coding RNAs typically involves effects on mRNA degradation and/or ribosomal translation. The possibility of virus-host mRNA-mRNA antisense tethering interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase) and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional significance of these ATIs is further supported by the observation that, in both viruses, they are located in close proximity to highly conserved in-frame UGA stop codons at the 3' end of open reading frames that encode essential viral proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation.

Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements.

PubMed

Duncan, Andrew; Talwar, Dinesh; McMillan, Donald C; Stefanowicz, Fiona; O'Reilly, Denis St J

2012-01-01

Plasma concentrations of several trace elements and vitamins decrease because of the systemic inflammatory response. Thus, low values do not necessarily indicate deficiency. The magnitude of this effect on plasma micronutrient concentrations was investigated to provide guidance on the interpretation of routine clinical results. Between 2001 and 2011, the results (2217 blood samples from 1303 patients) of routine micronutrient screens (plasma zinc, copper, selenium, and vitamins A, B-6, C, and E) and all vitamin D results (4327 blood samples from 3677 patients) were extracted from the laboratory database. C-reactive protein concentrations were measured as a marker of the severity of inflammation and categorized into 6 groups; for each group, plasma micronutrient concentrations and percentage changes were calculated. Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severities of the acute inflammatory response. For selenium and vitamins B-6 and C, this occurred with only slightly increased C-reactive protein concentrations of 5 to 10 mg/L. For each micronutrient, the change in plasma concentrations varied markedly from patient to patient. The magnitude of the effect was greatest for selenium and vitamins A, B-6, C, and D, for which the median plasma concentrations decreased by >40%. The clinical interpretation of plasma micronutrients can be made only with knowledge of the degree of inflammatory response. A reliable clinical interpretation can be made only if the C-reactive protein is <20 mg/L (plasma zinc), <10 mg/L (plasma selenium and vitamins A and D), or <5 mg/L (vitamins B-6 and C).

Toxicity and oxidative stress of different forms of organic selenium and dietary protein in mallard ducklings

USGS Publications Warehouse

Hoffman, D.J.; Heinz, G.H.; LeCaptain, L.J.; Eisemann, J.D.; Pendleton, G.W.

1996-01-01

Concentrations of over 100 ppm (mg/kg) selenium (Se) have been found in aquatic plants and insects associated with irrigation drainwater and toxicity to fish and wildlife. Composition of diet for wild ducklings may vary in selenium-contaminated environments. Earlier studies have compared toxicities and oxidative stress of Se as selenite to those of seleno-DL-methionine (DL) in mallards (Anas platyrhynchos). This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms except for 30 ppm Se as W. After 2 weeks blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L at 30 ppm in the diet was the most toxic form, resulting in high mortality (64%) and impaired growth (>50%) in survivors and the greatest increase in ratio of oxidized to reduced hepatic glutathione (GSH). Se as both L and DL decreased the concentrations of hepatic GSH and total thiols. Se as Y accumulated the least in liver (approximately 50% of other forms) and had less effect on GSH and total thiols. In a second experiment, in which the basal diet was a commercial duck feed (22 % protein), survival was not affected by 30 ppm Se as DL, L, or Y and oxidative effects on GSH metabolism were less pronounced than with the wheat diet.

Selenocysteine in thiol/disulfide-like exchange reactions.

PubMed

Hondal, Robert J; Marino, Stefano M; Gladyshev, Vadim N

2013-05-01

Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec.

Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil.

PubMed

Payne, N Connor; Geissler, Andrew; Button, Aileen; Sasuclark, Alexandru R; Schroll, Alayne L; Ruggles, Erik L; Gladyshev, Vadim N; Hondal, Robert J

2017-03-01

Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNA Glu , tRNA Gln and tRNA Lys . It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulfur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulfur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulfur-containing 2-thiouracil-5-carboxylic acid (s 2 c 5 Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se 2 c 5 Ura) using 1 H-NMR spectroscopy, 77 Se-NMR spectroscopy, and liquid chromatography-mass spectrometry. Treatment of s 2 c 5 Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c 5 Ura). In contrast, se 2 c 5 Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s 2 c 5 Ura, whereas very little deselenization of se 2 c 5 Ura occurred in the presence of the same antioxidants. In addition, se 2 c 5 Ura but not s 2 c 5 Ura showed glutathione peroxidase activity, further suggesting that oxidation of se 2 c 5 Ura is readily reversible, while oxidation of s 2 c 5 Ura is not. The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology. Copyright © 2017. Published by Elsevier Inc.

Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil✰

PubMed Central

Payne, N. Connor; Geissler, Andrew; Button, Aileen; Sasuclark, Alexandru R.; Schroll, Alayne L.; Ruggles, Erik L.; Gladyshev, Vadim N.; Hondal, Robert J.

2017-01-01

Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNAGlu, tRNAGln and tRNALys. It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulfur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulfur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulfur-containing 2-thiouracil-5-carboxylic acid (s2c5Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se2c5Ura) using 1H-NMR spectroscopy, 77Se-NMR spectroscopy, and liquid chromatography-mass spectrometry. Treatment of s2c5Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c5Ura). In contrast, se2c5Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s2c5Ura, whereas very little deselenization of se2c5Ura occurred in the presence of the same antioxidants. In addition, se2c5Ura but not s2c5Ura showed glutathione peroxidase activity, further suggesting that oxidation of se2c5Ura is readily reversible, while oxidation of s2c5Ura is not. The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology. PMID:28108278

Regulation of Selenoproteins and Methionine Sulfoxide Reductases A and B1 by Age, Calorie Restriction, and Dietary Selenium in Mice

PubMed Central

Novoselov, Sergey V.; Kim, Hwa-Young; Hua, Deame; Lee, Byung Cheon; Astle, Clinton M.; Harrison, David E.; Friguet, Bertrand; Moustafa, Mohamed E.; Carlson, Bradley A.; Hatfield, Dolph L.

2010-01-01

Abstract Methionine residues are susceptible to oxidation, but this damage may be reversed by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the major methionine sulfoxide reductase in liver of mice and it is among the proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA activities, were reduced with age, and the selenium regulation of MsrB1 was preserved in the aging liver, suggesting that MsrB1 could account for the impaired methionine sulfoxide reduction in aging animals. We also examined regulation of Msr and selenoprotein expression by a combination of dietary selenium and calorie restriction and found that, under calorie restriction conditions, selenium regulation was preserved. In addition, mice overexpressing a mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed in selenium deficiency, whereas MsrA activity was elevated in these animals. Finally, we show that selenium regulation in inbred mouse strains is preserved in an outbred aging model. Taken together, these findings better define dietary regulation of methionine sulfoxide reduction and selenoprotein expression in mice with regard to age, calorie restriction, dietary Se, and a combination of these factors. Antioxid. Redox Signal. 12, 829–838. PMID:19769460

Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention?

PubMed Central

Diamond, Alan M.

2013-01-01

The trace element selenium is an essential micronutrient that has received considerable attention for its potential use in the prevention of cancer. In spite of this interest, the mechanism(s) by which selenium might function as a chemopreventive remain to be determined. Considerable experimental evidence indicates that one possible mechanism by which selenium supplementation may exert its benefits is by enhancing the DNA damage repair response, and this includes data obtained using cultured cells, animal models as well as in human clinical studies. In these studies, selenium supplementation has been shown to be beneficial in reducing the frequency of DNA adducts and chromosome breaks, consequentially reducing the likelihood of detrimental mutations that ultimately contribute to carcinogenesis. The benefits of selenium can be envisioned as being due, at least in part, to it being a critical constituent of selenoproteins such as glutathione peroxidases and thioredoxin reductases, proteins that play important roles in antioxidant defence and maintaining the cellular reducing environment. Selenium, therefore, may be protective by preventing DNA damage from occurring as well as by increasing the activity of repair enzymes such as DNA glycosylases and DNA damage repair pathways that involve p53, BRCA1 and Gadd45. An improved understanding of the mechanism of selenium’s impact on DNA repair processes may help to resolve the apparently contradicting data obtained from decades of animal work, human epidemiology and more recently, clinical supplementation studies. PMID:23204505

Effects of exendin-4 and selenium on the expression of GLP-1R, IRS-1, and preproinsulin in the pancreas of diabetic rats.

PubMed

Barakat, Ghinwa; Moustafa, Mohamed E; Khalifeh, Ibrahim; Hodroj, Mohammad H; Bikhazi, Anwar; Rizk, Sandra

2016-08-01

The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.

Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial.

PubMed

Alizadeh, Mohammad; Safaeiyan, Abdolrasoul; Ostadrahimi, Alireza; Estakhri, Rassul; Daneghian, Sevana; Ghaffari, Aida; Gargari, Bahram Pourghassem

2012-01-01

We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 μg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO(x)), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO(x). HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO(x) and TG. Copyright © 2012 S. Karger AG, Basel.

Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice.

PubMed

Dong, Ruixia; Wang, Dongxu; Wang, Xiaoxiao; Zhang, Ke; Chen, Pingping; Yang, Chung S; Zhang, Jinsong

2016-12-01

Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2010-04-01

finasteride decreases the formation of DHT, while MSA depresses the abundance of AR protein. To study the effect of finasteride/MSA on FOXO1...chemoprevention based on selenium suppression of androgen signaling”. 4. AACR Centennial Meeting, Los Angeles, CA, April 15-18, poster presentation...AR mRNA level was depressed by 0%, 20%, or 60%, respec- tively; AR transactivation was inhibited by 35%, 10%, or 60%, respectively; whereas the PSA

Down-regulation of ATF2 in the inhibition of T-2-toxin-induced chondrocyte apoptosis by selenium chondroitin sulfate nanoparticles

NASA Astrophysics Data System (ADS)

Han, Jing; Guo, Xiong

2013-12-01

Selenium chondroitin sulfate nanoparticles (SeCS) with a size range of 30-200 nm were obtained in our previous study. Meanwhile, the up-regulated expression of ATF2 mRNA and protein levels could be observed in the cartilage from Kashin-Beck disease (KBD) patients. In this paper, we investigated the inhibition effect of SeCS on T-2-toxin-induced apoptosis of chondrocyte from KBD patients. Here, we found that when the chondrocytes were treated with T-2 toxin, the chondrocyte apoptosis performed in a concentration-dependent manner. The apoptosis of chondrocyte induced by T-2 toxin involved the increased levels of ATF2, JNK and p38 mRNAs and related protein expression. SeCS could partly block the T-2-toxin-induced chondrocyte apoptosis by decreasing the expression of ATF2, JNK and p38 mRNAs and p-JNK, p-38, ATF2 and p-ATF2 proteins. JNK and p38 pathways involved in the apoptosis of chondrocyte induced by T-2 toxin, and SeCS was efficient in the inhibition of chondrocyte apoptosis by T-2 toxin. These results suggested that SeCS had a potential for further prevention and treatment for KBD as well as other selenium deficiency disease.

Selenium-Dependent Biogenesis of Formate Dehydrogenase in Campylobacter jejuni Is Controlled by the fdhTU Accessory Genes

PubMed Central

Shaw, Frances L.; Mulholland, Francis; Le Gall, Gwénaëlle; Porcelli, Ida; Hart, Dave J.; Pearson, Bruce M.

2012-01-01

The food-borne bacterial pathogen Campylobacter jejuni efficiently utilizes organic acids such as lactate and formate for energy production. Formate is rapidly metabolized via the activity of the multisubunit formate dehydrogenase (FDH) enzyme, of which the FdhA subunit is predicted to contain a selenocysteine (SeC) amino acid. In this study we investigated the function of the cj1500 and cj1501 genes of C. jejuni, demonstrate that they are involved in selenium-controlled production of FDH, and propose the names fdhT and fdhU, respectively. Insertional inactivation of fdhT or fdhU in C. jejuni resulted in the absence of FdhA and FdhB protein expression, reduced fdhABC RNA levels, the absence of FDH enzyme activity, and the lack of formate utilization, as assessed by 1H nuclear magnetic resonance. The fdhABC genes are transcribed from a single promoter located two genes upstream of fdhA, and the decrease in fdhABC RNA levels in the fdhU mutant is mediated at the posttranscriptional level. FDH activity and the ability to utilize formate were restored by genetic complementation with fdhU and by supplementation of the growth media with selenium dioxide. Disruption of SeC synthesis by inactivation of the selA and selB genes also resulted in the absence of FDH activity, which could not be restored by selenium supplementation. Comparative genomic analysis suggests a link between the presence of selA and fdhTU orthologs and the predicted presence of SeC in FdhA. The fdhTU genes encode accessory proteins required for FDH expression and activity in C. jejuni, possibly by contributing to acquisition or utilization of selenium. PMID:22609917

Effect of high-dose nano-selenium and selenium-yeast on feed digestibility, rumen fermentation, and purine derivatives in sheep.

PubMed

Xun, Wenjuan; Shi, Liguang; Yue, Wenbin; Zhang, Chunxiang; Ren, Youshe; Liu, Qiang

2012-12-01

The aim of this study was to evaluate the effect of nano-selenium (NS) and yeast-selenium (YS) supplementation on feed digestibility, rumen fermentation, and urinary purine derivatives in sheep. Six male ruminally cannulated sheep, average 43.32 ± 4.8 kg of BW, were used in a replicated 3 × 3 Latin square experiment. The treatments were control (without NS and YS), NS with 4 g nano-Se (provide 4 mg Se), and YS with 4 g Se-yeast (provide 4 mg Se) per kilogram of diet dry matter (DM), respectively. Experimental periods were 25 days with 15 days of adaptation and 10 days of sampling. Ruminal pH, ammonia N concentration, molar proportion of propionate, and ratio of acetate to propionate were decreased (P < 0.01), and total ruminal VFA concentration was increased with NS and YS supplementation (P < 0.01). In situ ruminal neutral detergent fiber (aNDF) degradation of Leymus chinensis (P < 0.01) and crude protein (CP) of soybean meal (P < 0.01) were significantly improved by Se supplementation. Digestibilities of DM, organic matter, crude protein, ether extract, aNDF, and ADF in the total tract and urinary excretion of purine derivatives were also affected by feeding Se supplementation diets (P < 0.01). Ruminal fermentation was improved by feeding NS, and feed conversion efficiency was also increased compared with YS (P < 0.01). We concluded that nano-Se can be used as a preferentially available selenium source in ruminant nutrition.

Enhanced antioxidant capacity following selenium supplemented antimalarial therapy in Plasmodium berghei infected mice

NASA Astrophysics Data System (ADS)

Adebayo, Abiodun Humphrey; Olasehinde, Grace Iyabo; Egbeola, Oluwaseun Ayodimeji; Yakubu, Omolara Faith; Adeyemi, Alaba Oladipupo; Adekeye, Bosede Temitope

2018-04-01

The effect of the co-administration of artemether, lumefantrine and selenium was studied in mice infected with Plasmodium bergheiparasite. The mice were divided into seven groups of six animals per group. All groups except A were parasitized. Group A (unparasitized/untreated) and B (parasitized/untreated) served as the positive and negative control respectively, these were administered with olive oil. Animals in groups C and D were treated with 8 and 48 mg/kg/bw of artemether and lumefantrine respectively while group E was treated with a combination of artemether and lumefantrine (8: 48 mg/kg/bw). Animals in group F were treated with 0.945 mg/kg/bw of selenium only and group G was treated with a combination of artemether, lumefantrine and selenium (8:48:0.945 mg/kg/bw). All the treatment was done for a three day period. These animals were subsequently anaesthetized and the organs were excised. Homogenates were prepared for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, reduced Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) assays. The results showed a significant (p<0.05) difference in the levels of ALP and MDA in group B, while a significant difference was observed in the levels of ALP, total protein, CAT and MDA in group G when compared with the parasitized group. Histopathological analysis showed no presence of inflammatory cells in group G when compared with group B. It may be concluded that the combination of artemether, lumefantrine and selenium showed a more potent effect against the parasite than the group treated with artemether and lumefantrine, thus, helps to combat post-infection oxidative stress in susceptible cells.

Environmental Issues in Thyroid Diseases.

PubMed

Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2017-01-01

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdur, Rob; Gerlits, Oksana O.; Gan, Jianhua

2014-02-01

Selenium-derivatized oligonucleotides may facilitate phase determination and high-resolution structure determination for protein–nucleic acid crystallography. The Se atom-specific mutagenesis (SAM) strategy may also enhance the study of nuclease catalysis. The crystal structures of protein–nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein–nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H–RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissilemore » phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage.« less

Extracellular polymeric substances govern the surface charge of biogenic elemental selenium nanoparticles.

PubMed

Jain, Rohan; Jordan, Norbert; Weiss, Stephan; Foerstendorf, Harald; Heim, Karsten; Kacker, Rohit; Hübner, René; Kramer, Herman; van Hullebusch, Eric D; Farges, François; Lens, Piet N L

2015-02-03

The origin of the organic layer covering colloidal biogenic elemental selenium nanoparticles (BioSeNPs) is not known, particularly in the case when they are synthesized by complex microbial communities. This study investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed the presence of functional groups characteristic of proteins and carbohydrates on the BioSeNPs, suggesting the presence of EPS. Chemical synthesis of elemental selenium nanoparticles in the presence of EPS, extracted from selenite fed anaerobic granular sludge, yielded stable colloidal spherical selenium nanoparticles. Furthermore, extracted EPS, BioSeNPs, and chemically synthesized EPS-capped selenium nanoparticles had similar surface properties, as shown by ζ-potential versus pH profiles and isoelectric point measurements. This study shows that the EPS of anaerobic granular sludge form the organic layer present on the BioSeNPs synthesized by these granules. The EPS also govern the surface charge of these BioSeNPs, thereby contributing to their colloidal properties, hence affecting their fate in the environment and the efficiency of bioremediation technologies.

Evaluation of the inorganic selenium biotransformation in selenium-enriched yogurt by HPLC-ICP-MS.

PubMed

Alzate, Adriana; Cañas, Benito; Pérez-Munguía, Sandra; Hernández-Mendoza, Hector; Pérez-Conde, Concepción; Gutiérrez, Ana Maria; Cámara, Carmen

2007-11-28

Selenium is an essential element in the human diet. Interestingly, there has been an increased consumption of dietary supplements containing this element in the form of either inorganic or organic compounds. The effect of using selenium as a dietary supplement in yogurt has been evaluated. For this purpose, different concentrations of inorganic Se (ranging from 0.2 to 5000 microg g(-1)) have been added to milk before the fermentation process. Biotransformation of inorganic Se into organic species has been carefully evaluated by ion-exchange, reversed-phase, or size-exclusion chromatography, coupled to inductively coupled plasma mass spectrometry (ICP-MS). Yogurt fermentation in the presence of up to 2 microg g(-1) of Se(IV) produces a complete incorporation of this element into proteins as has been demonstrated applying a dialysis procedure. Analysis by SEC-ICP-MS showed that most of them have a molecular mass in the range of 30-70 kDa. Species determination after enzymatic hydrolysis has allowed the identification of Se-cystine using two different chromatographic systems. The biotransformation process that takes place during yogurt fermentation is very attractive because yogurt can act as a source of selenium supplementation.

Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency

PubMed Central

2014-01-01

Introduction Low plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status. Method A prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 μmol/L to 1.6 μmol/L. The outcome variable was ‘low plasma selenium’, which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses. Results Malnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16). Conclusions There is a significant interaction between the magnitude of the inflammatory response and malnutrition on low plasma selenium. This interaction should be considered when interpreting plasma concentrations as an index of selenium status in patients with systemic inflammation as well as in the decision on selenium supplementation. PMID:24886623

Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry

PubMed Central

Taylor, Ethan Will; Ruzicka, Jan A.; Premadasa, Lakmini; Zhao, Lijun

2016-01-01

Regulation of protein expression by non-coding RNAs typically involves effects on mRNA degradation and/or ribosomal translation. The possibility of virus-host mRNA-mRNA antisense tethering interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase) and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional significance of these ATIs is further supported by the observation that, in both viruses, they are located in close proximity to highly conserved in-frame UGA stop codons at the 3′ end of open reading frames that encode essential viral proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation. PMID:26369818

An Overview of Selenium Uptake, Metabolism, and Toxicity in Plants

PubMed Central

Gupta, Meetu; Gupta, Shikha

2017-01-01

Selenium (Se) is an essential micronutrient for humans and animals, but lead to toxicity when taken in excessive amounts. Plants are the main source of dietary Se, but essentiality of Se for plants is still controversial. However, Se at low doses protects the plants from variety of abiotic stresses such as cold, drought, desiccation, and metal stress. In animals, Se acts as an antioxidant and helps in reproduction, immune responses, thyroid hormone metabolism. Selenium is chemically similar to sulfur, hence taken up inside the plants via sulfur transporters present inside root plasma membrane, metabolized via sulfur assimilatory pathway, and volatilized into atmosphere. Selenium induced oxidative stress, distorted protein structure and function, are the main causes of Se toxicity in plants at high doses. Plants can play vital role in overcoming Se deficiency and Se toxicity in different regions of the world, hence, detailed mechanism of Se metabolism inside the plants is necessary for designing effective Se phytoremediation and biofortification strategies. PMID:28123395

Expression of glutathione peroxidase I gene in selenium-deficient rats.

PubMed Central

Reddy, A P; Hsu, B L; Reddy, P S; Li, N Q; Thyagaraju, K; Reddy, C C; Tam, M F; Tu, C P

1988-01-01

We have characterized a cDNA pGPX1211 encoding rat glutathione peroxidase I. The selenocysteine in the protein corresponded to a TGA codon in the coding region of the cDNA, similar to earlier findings in mouse and human genes, and a gene encoding the formate dehydrogenase from E. coli, another selenoenzyme. The rat GSH peroxidase I has a calculated subunit molecular weight of 22,155 daltons and shares 95% and 86% sequence homology with the mouse and human subunits, respectively. The 3'-noncoding sequence (greater than 930 bp) in pGPX1211 is much longer than that of the human sequences. We found that glutathione peroxidase I mRNA, but not the polypeptide, was expressed under nutritional stress of selenium deficiency where no glutathione peroxidase I activity can be detected. The failure of detecting any apoprotein for the glutathione peroxidase I under selenium deficiency and results published from other laboratories supports the proposal that selenium may be incorporated into the glutathione peroxidase I co-translationally. Images PMID:2838821

Selenocysteine in Thiol/Disulfide-Like Exchange Reactions

PubMed Central

Marino, Stefano M.

2013-01-01

Abstract Significance: Among trace elements used as cofactors in enzymes, selenium is unique in that it is incorporated into proteins co-translationally in the form of an amino acid, selenocysteine (Sec). Sec differs from cysteine (Cys) by only one atom (selenium versus sulfur), yet this switch dramatically influences important aspects of enzyme reactivity. Recent Advances: The main focus of this review is an updated and critical discussion on how Sec might be used to accelerate thiol/disulfide-like exchange reactions in natural selenoenzymes, compared with their Cys-containing homologs. Critical Issues: We discuss in detail three major aspects associated with thiol/disulfide exchange reactions: (i) nucleophilicity of the attacking thiolate (or selenolate); (ii) electrophilicity of the center sulfur (or selenium) atom; and (iii) stability of the leaving group (sulfur or selenium). In all these cases, we analyze the benefits that selenium might provide in these types of reactions. Future Directions: It is the biological thiol oxidoreductase-like function that benefits from the use of Sec, since Sec functions to chemically accelerate the rate of these reactions. We review various hypotheses that could help explain why Sec is used in enzymes, particularly with regard to competitive chemical advantages provided by the presence of the selenium atom in enzymes. Ultimately, these chemical advantages must be connected to biological functions of Sec. Antioxid. Redox Signal. 18, 1675–1689. PMID:23121622

Selenium Supplementation and the Effects on Reproductive Outcomes, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome.

PubMed

Razavi, M; Jamilian, M; Kashan, Z Fakhrieh; Heidar, Z; Mohseni, M; Ghandi, Y; Bagherian, T; Asemi, Z

2016-03-01

Selenium supplementation could be effective on reproductive outcomes, biomarkers of inflammation, and oxidative stress among women with polycystic ovary syndrome (PCOS). The aim of the study was to determine the effects of selenium supplementation on reproductive outcomes, biomarkers of inflammation, and oxidative stress in PCOS patients. The present randomized double-blind, placebo-controlled trial was conducted on 64 women aged 18-40 years old with PCOS at the clinic affiliated to Ardabil University of Medical Sciences, Ardabil, Iran. The participants were randomly assigned to 2 groups receiving either 200 μg selenium daily (n=32) or placebo (n=32) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured and compared both before and after the treatment. After 8 weeks of intervention, pregnancy rate in the selenium group was higher than in the placebo group: 18.8 (6/32) vs. 3.1% (1/32), p=0.04. In addition, alopecia (40.6 vs. 9.4%, p=0.004) and acne (46.9 vs. 12.5 %, p=0.003) decreased following the consumption of selenium supplements compared with placebo. Additionally, patients who received selenium supplements had significantly decreased serum dehydroepiandrosterone (DHEA) levels (p=0.02), hirsutism (modified Ferriman-Gallwey scores) (p<0.001), serum high sensitivity C-reactive protein (hs-CRP) (p=0.02), and plasma malondialdehyde (MDA) levels (p=0.01) compared with placebo. We did not observe any significant effects of taking selenium supplements on other hormonal profiles, nitric oxide (NO), and other biomarkers of oxidative stress. Taken together, selenium supplementation for 8 weeks among PCOS women had beneficial effects on reproductive outcomes, DHEA, hs-CRP, and MDA levels. Supporting Information for this article is available online at http://www.thieme-connect.de/products. © Georg Thieme Verlag KG Stuttgart · New York.

Nuclear blebbing of biologically active organoselenium compound towards human cervical cancer cell (HeLa): in vitro DNA/HSA binding, cleavage and cell imaging studies.

PubMed

Rizvi, Masood Ahmad; Zaki, Mehvash; Afzal, Mohd; Mane, Manoj; Kumar, Manjeet; Shah, Bhahwal Ali; Srivastav, Saurabh; Srikrishna, Saripella; Peerzada, Ghulam Mustafa; Tabassum, Sartaj

2015-01-27

New pharmacophore organoselenium compound (1) was designed, synthesized and characterized by various spectroscopic methods (IR, ESI-MS, (1)H, (13)C and (77)Se NMR) and further confirmed by X-ray crystallography. Compound 1 consists of two 3,5-bis(trifluoromethyl)phenyl units which are connected to the selenium atom via the organometallic C-Se bond. In vitro DNA binding studies of 1 was investigated by absorption and emission titration methods which revealed that 1 recognizes the minor groove of DNA in accordance with molecular docking studies with the DNA duplex. Gel electrophoretic assay demonstrates the ability of 1 to cleave pBR322 DNA through hydrolytic process which was further validated by T4 religation assay. To understand the drug-protein interaction of which ultimate molecular target was DNA, the affinity of 1 towards HSA was also investigated by the spectroscopic and molecular modeling techniques which showed hydrophobic interaction in the subdomain IIA of HSA. Furthermore, the intracellular localization of 1 was evidenced by cell imaging studies using HeLa cells. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Selenium bioavailability from soy protein isolate and tofu in rats fed a torula yeast-based diet.

PubMed

Yan, Lin; Graef, George L; Reeves, Philip G; Johnson, LuAnn K

2009-12-23

Selenium (Se) is an essential nutrient, and soy is a major plant source of dietary protein to humans. The United States produces one-third of the world's soybeans, and the Se-rich Northern Plains produce a large share of the nation's soybeans. The present study used a rat model to determine the bioavailability of Se from a protein isolate and tofu (bean curd) prepared from a soybean cultivar we recently developed specifically for food grade markets. The soybean seeds contained 2.91 mg Se/kg. Male Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet containing 5 microg Se/kg; after 56 days, they were replenished of Se for an additional 50 days by feeding them the same diet supplemented with 20, 30, or 40 microg Se/kg from soy protein isolate or tofu. l-Selenomethionine (SeMet) was used as a reference. Selenium bioavailability was determined on the basis of the responses of Se-dependent enzyme activities and tissue Se contents, comparing those responses for each soy product to those for SeMet using a slope-ratio method. Dietary supplementation with the protein isolate or tofu resulted in dose-dependent increases in glutathione peroxidase activities in blood and liver and thioredoxin reductase activity in liver, as well as dose-dependent increases in the Se contents of plasma, liver, muscle, and kidneys. These responses indicated an overall bioavailability of approximately 97% for Se from both the protein isolate and tofu, relative to SeMet. These results demonstrate that Se from this soybean cultivar is highly bioavailable in this model and that high-Se soybeans can be good dietary sources of Se.

Influence of selenium supplementation on patients with inflammation: A pilot double blind randomized study.

PubMed

Freitas, Renata Germano Borges de Oliveira Nascimento; Nogueira, Roberto José Negrão; Cozzolino, Silvia Maria Franciscato; Vasques, Ana Carolina Junqueira; Hessel, Gabriel

2017-09-01

The aim of the study was to analyze the effect of selenium supplementation on patients with inflammation receiving PN. This double-blind randomized study included 20 hospitalized patients experiencing an inflammatory process while being fed by PN, who were monitored in three stages: first 72 h (0), day 7 (1), and day 14 (2) of PN. The supplemented patients group (G+S) received 60 μg/d (0.75 μmol) of selenium as selenious acid which was added to the PN bag. The nonsupplemented group (G-S) did not receive selenium. The concentration range of 84 to 100 μg/L (1.07-1.27 μmol/L) was used as a reference of plasma selenium. The study included 20 patients (8 G+S and 12 G-S) mainly diagnosed with cancer and/or sepsis. Most of them were hospitalized in the intensive care unit and were receiving PN for clinical reasons. Plasma selenium was greater in the G+S than in the G-S (P = 0.05) in two stages (0 and 1). Since the start of assessment, C-reactive protein (CRP) levels were elevated; however, there was no statistical difference in CRP values between groups (P > 0.05). There was no significant change of glutathione peroxidase over time or between groups (P > 0.05). The selenium concentration was greater in the G+S than in the G-S, acting independently from CRP behavior. However, supplementation was not enough to reach the reference values. Copyright © 2017 Elsevier Inc. All rights reserved.

Selenoamino Acid-Enriched Green Pea as a Value-Added Plant Protein Source for Humans and Livestock.

PubMed

Garousi, Farzaneh; Domokos-Szabolcsy, Éva; Jánószky, Mihály; Kovács, Andrea Balláné; Veres, Szilvia; Soós, Áron; Kovács, Béla

2017-06-01

Selenium deficiency in various degrees affects around 15% of the world's population, contributing to a variety of health problems. In this study, we examined the accumulation and biotransformation of soil applied Se-supplementation (sodium selenite and sodium selenate forms) at different concentrations, along with growth and yield formation of green pea, in a greenhouse experiment. Biotransformation of inorganic Se was evaluated using HPLC-ICP-MS for Se-species separation in the above ground parts of green pea. Results showed 3 mg kg -1 Se IV increased green pea growth biomarkers and also caused an increase in protein content in leaves by 17%. Selenomethionine represented 65% of the total selenium content in shoots, but was lower in pods and seeds (54 and 38%, respectively). Selenomethionine was the major species in all plant parts and the only organic selenium form in the lower Se IV concentration range. Elevating the dose of Se IV (≥30 mg kg -1 ) triggered detrimental effects on growth and protein content and caused higher accumulation of inorganic Se in forms of Se VI and Se IV . Selenocysteine, another organic form of proteinogenic amino acid, was determined when Se IV (≥10 mg kg -1 ) was applied in higher concentrations. Thus, agronomic biofortification using the appropriate chemical form and concentration of Se will have positive effects on green pea growth and its enriched shoots and seeds provide a value-added protein source for livestock and humans with significant increased selenomethionine.

Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Mesdaghinia, Elaheh; Rahavi, Azam; Bahmani, Fereshteh; Sharifi, Nasrin; Asemi, Zatollah

2017-07-01

Data on the effects of selenium supplementation on clinical signs and metabolic profiles in women at risk for intrauterine growth restriction (IUGR) are scarce. This study was designed to assess the effects of selenium supplementation on clinical signs and metabolic status in pregnant women at risk for IUGR. This randomized double-blind placebo-controlled clinical trial was performed among 60 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to intake either 100 μg selenium supplements as tablet (n = 30) or placebo (n = 30) for 10 weeks between 17 and 27 weeks of gestation. After 10 weeks of selenium administration, a higher percentage of women in the selenium group had pulsatility index (PI) of <1.45) (P = 0.002) than of those in the placebo group. In addition, changes in plasma levels of total antioxidant capacity (TAC) (P < 0.001), glutathione (GSH) (P = 0.008), and high-sensitivity C-reactive protein (hs-CRP) (P = 0.004) in the selenium group were significant compared with the placebo group. Additionally, selenium supplementation significantly decreased serum insulin (P = 0.02), homeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.02), and homeostatic model assessment for B-cell function (HOMA-B) (P = 0.02) and significantly increased quantitative insulin sensitivity check index (QUICKI) (P = 0.04) and HDL-C levels (P = 0.02) compared with the placebo. We did not find any significant effect of selenium administration on malondialdehyde (MDA), nitric oxide (NO), fasting plasma glucose (FPG), and other lipid profiles. Overall, selenium supplementation in pregnant women at risk for IUGR resulted in improved PI, TAC, GSH, hs-CRP, and markers of insulin metabolism and HDL-C levels, but it did not affect MDA, NO, FPG, and other lipid profiles.Clinical trial registration number http://www.irct.ir : IRCT201601045623N64.

Selenite reduction by the thioredoxin system: kinetics and identification of protein-bound selenide.

PubMed

Tamura, Takashi; Sato, Kumi; Komori, Kentaro; Imai, Takeshi; Kuwahara, Mitsuhiko; Okugochi, Takahiro; Mihara, Hisaaki; Esaki, Nobuyoshi; Inagaki, Kenji

2011-01-01

Selenite (SeO(3)(2-)) assimilation into a bacterial selenoprotein depends on thioredoxin (trx) reductase in Esherichia coli, but the molecular mechanism has not been elucidated. The mineral-oil overlay method made it possible to carry out anaerobic enzyme assay, which demonstrated an initial lag-phase followed by time-dependent steady NADPH consumption with a positive cooperativity toward selenite and trx. SDS-PAGE/autoradiography using (75)Se-labeled selenite as substrate revealed the formation of trx-bound selenium in the reaction mixture. The protein-bound selenium has metabolic significance in being stabilized in the divalent state, and it also produced the selenopersulfide (-S-SeH) form by the catalysis of E. coli trx reductase (TrxB).

Biogenesis of Selenium Nanoparticles Using Green Chemistry.

PubMed

Shoeibi, Sara; Mozdziak, Paul; Golkar-Narenji, Afsaneh

2017-11-09

Selenium binds some enzymes such as glutathione peroxidase and thioredoxin reductase, which may be activated in biological infections and oxidative stress. Chemical and physical methods for synthesizing nanoparticles, apart from being expensive, have their own particular risks. However, nanoparticle synthesis through green chemistry is a safe procedure that different biological sources such as bacteria, fungi, yeasts, algae and plants can be the catalyst bed for processing. Synthesis of selenium nanoparticles (SeNPs) by macro/microorganisms causes variation in morphology and shape of the particles is due to diversity of reduction enzymes in organisms. Reducing enzymes of microorganisms by changing the status of redox convert metal ions (Se 2- ) to SeNPs without charge (Se 0 ). Biological activity of SeNPs includes their protective role against DNA oxidation. Because of the biological and industrial properties, SeNPs have wide applications in the fields of medicine, microelectronic, agriculture and animal husbandry. SeNPs can show strong antimicrobial effects on the growth and proliferation of microorganisms in a dose-dependent manner. The objective of this review is to consider SeNPs applications to various organisms.

Transcriptome analysis of differentially expressed genes involved in selenium accumulation in tea plant (Camellia sinensis)

PubMed Central

Liu, Yanli; Ma, Linlong; Jin, Xiaofang; Guo, Guiyi; Tan, Rongrong; Liu, Zheng; Zheng, Lin; Ye, Fei; Liu, Wei

2018-01-01

Tea plant (Camellia sinensis) has strong enrichment ability for selenium (Se). Selenite is the main form of Se absorbed and utilized by tea plant. However, the mechanism of selenite absorption and accumulation in tea plant is still unknown. In this study, RNA sequencing (RNA-seq) was used to perform transcriptomic analysis on the molecular mechanism of selenite absorption and accumulation in tea plant. 397.98 million high-quality reads were obtained and assembled into 168,212 unigenes, 89,605 of which were extensively annotated. There were 60,582 and 1,362 differentially expressed genes (DEGs) in roots and leaves, respectively. RNA-seq results were further validated by quantitative RT-PCR. Based on GO terms, the unigenes were mainly involved in cell, binding and metabolic process. KEGG pathway enrichment analysis showed that predominant pathways included ribosome and protein processing in endoplasmic reticulum. Further analysis revealed that sulfur metabolism, glutathione metabolism, selenocompound metabolism and plant hormone signal transduction responded to selenite in tea plant. Additionally, a large number of genes of higher expressions associated with phosphate transporters, sulfur assimilation, antioxidant enzymes, antioxidant substances and responses to ethylene and jasmonic acid were identified. Stress-related plant hormones might play a signaling role in promoting sulfate/selenite uptake and assimilation in tea plant. Moreover, some other Se accumulation mechanisms of tea plant were found. Our study provides a possibility for controlling Se accumulation in tea plant through bio-technologies and will be helpful for breeding new tea cultivars. PMID:29856771

Long-term dietary supplementation of organic selenium modulates gene expression profiles in leukocytes of adult pigs.

PubMed

Song, Ki-Duk; Dowd, Scott E; Lee, Hak-Kyo; Kim, Sung Woo

2013-03-01

Seventy-two pigs at 34.4 kg body weight (BW) were allotted to two treatments with six replicates/treatment and six pigs/pen: the CON (negative control, no added selenium (Se)) and the OS (0.36 mg/kg added selenium from selenium-enriched yeast). Pigs were fed until 130 kg BW. The CON diet contained 0.18 mg/kg indigenous Se whereas the OS diet contained 0.54 mg/kg Se. Blood samples were collected at 130 kg BW and further processed for microarray analysis, prepared with 885 genes related to immune function of pigs. Among those, 28 genes related to improved immune status and innate immunity were up-regulated (P < 0.05) in leukocytes from Se-fed pigs and those include major histocompatibility class I (> 1.66), arginase I (> 1.27), integrin beta-1-subunit (> 1.20), toll like receptor 2 (> 1.12) and double-stranded RNA-dependent protein kinase. However, 24 genes including tissue factor (< 4.70), serum amyloid A-2 protein (< 3.11) and p27Kip1 (< 1.42) were down-regulated (P < 0.05) in leukocytes from Se-fed pigs. Expression of four selected genes was validated using quantitative PCR (qPCR) showing significant correlation between mircroarray analysis and qPCR analysis. This study indicates that a long- term dietary supplementation (0.3%) of organic Se improves the expression of genes that are related to enhanced immunity of pigs. © 2012 Japanese Society of Animal Science.

Selenium nanoparticles synthesized in aqueous extract of Allium sativum perturbs the structural integrity of Calf thymus DNA through intercalation and groove binding.

PubMed

Ezhuthupurakkal, Preedia Babu; Polaki, Lokeswara Rao; Suyavaran, Arumugam; Subastri, Ariraman; Sujatha, Venugopal; Thirunavukkarasu, Chinnasamy

2017-05-01

Biomedical application of selenium nanoparticles (SeNPs) demands the eco-friendly composite for synthesis of SeNPs. The present study reports an aqueous extract of Allium sativum (AqEAS) plug-up the current need. Modern spectroscopic, microscopic and gravimetric techniques were employed to characterize the synthesized nanoparticles. Characterization studies revealed the formation of crystalline spherical shaped SeNPs. FTIR spectrum brings out the presence of different functional groups in AqEAS, which influence the SeNPs formation and stabilization. Furthermore the different aspects of the interaction between SeNPs and CT-DNA were scrutinized by various spectroscopic and cyclic voltametric studies. The results reveals the intercalation and groove binding mode of interaction of SeNPs with stacked base pair of CT-DNA. The Stern-Volmer quenching constant (K SV ) were found to be 7.02×10 6 M- 1 (ethidium bromide), 4.22×10 6 M- 1 (acridine orange) and 7.6×10 6 M- 1 (Hoechst) indicating strong binding of SeNPs with CT-DNA. The SeNPs - CT-DNA interactions were directly visualized by atomic force microscopy. The present study unveils the cost effective, innocuous, highly stable SeNPs intricate mechanism of DNA interaction, which will be a milestone in DNA targeted chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice*

PubMed Central

Kasaikina, Marina V.; Fomenko, Dmitri E.; Labunskyy, Vyacheslav M.; Lachke, Salil A.; Qiu, Wenya; Moncaster, Juliet A.; Zhang, Jie; Wojnarowicz, Mark W.; Natarajan, Sathish Kumar; Malinouski, Mikalai; Schweizer, Ulrich; Tsuji, Petra A.; Carlson, Bradley A.; Maas, Richard L.; Lou, Marjorie F.; Goldstein, Lee E.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteine-rich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15 KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation. We suggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency. PMID:21768092

Epigenetic Regulation of Inflammatory Gene Expression in Macrophages by Selenium

PubMed Central

Narayan, Vivek; Ravindra, Kodihalli C.; Liao, Chang; Kaushal, Naveen; Carlson, Bradley A.; Prabhu, K. Sandeep

2014-01-01

Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of pro-inflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of selenium towards histone acetylation was examined in both in vitro and in vivo models of inflammation by chromatin immunoprecipitation (ChIP) assays and immunoblotting. Our results indicated that selenium supplementation, as selenite, decreased acetylation of histone H4 at K12 and K16 in COX-2 and TNF promoters, and of the p65 subunit of the redox sensitive transcription factor NFκB in primary and immortalized macrophages. On the other hand, selenomethionine had a much weaker effect. Selenite treatment of HIV-1 infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the downregulation of proviral expression by selenium. A similar decrease in histone acetylation was also seen in the colonic extracts of mice treated with dextran sodium sulfate that correlated well with the levels of selenium in the diet. Bone marrow-derived macrophages from Trspfl/flCreLysM mice that lack expression of selenoproteins in macrophages confirmed the important role of selenoproteins in the inhibition of histone H4 acetylation. Our studies suggest that the ability of selenoproteins to skew the metabolism of arachidonic acid to contribute, in part, to their ability to inhibit histone acetylation. In summary, our studies suggest a new role for selenoproteins in the epigenetic modulation of pro-inflammatory genes. PMID:25458528

Probing for the Activities of Arsenic and Selenium Metabolizing Microbes

NASA Astrophysics Data System (ADS)

Stolz, J. F.

2007-12-01

Microbial activities can directly impact the mobility and toxicity of arsenic and selenium in the environment. Arsenic is cycled through oxidation/reduction and methylation/demethylation reactions as part of resistance and respiratory processes. The requirement for selenium is primarily for incorporation into selenocysteine and its function in selenoenzymes. Selenium oxyanions can also serve as an electron acceptor in anaerobic respiration. Both culture and culture-independent methods have been developed to detect the presence and activity of organisms capable of arsenic and selenium transformations. Enrichment media have been successful at cultivating arsenate respiring bacteria from a variety of environments, however, both electron donor and the concentration of arsenic can exert strong selective pressure. Thus, the organisms in the enrichment culture may not be the dominant organisms in the environment. Culture-independent methods, including immunological approaches (e.g., polyclonal antibodies to ArrA) and PCR-based technologies, have also had mixed success. PCR-primers designed to amplify portions of genes involved in resistance (e.g., arsC, acr3), respiration (e.g., arrA), and oxidation (e.g., aoxB) have been useful in several environments. Applications include T-RFLP, rt-PCR, and DGGE analyses. Nevertheless, these primers do not work with certain organisms suggesting the existence of additional enzymes and pathways. Although the biosynthetic pathway (and the proteins involved) for selenocysteine has been described in detail, much less is known about selenium methylation, assimilation and respiration. Only one respiratory selenate reductase has been characterized and its close sequence identity with chlorate and perchlorate reductases has complicated efforts to design a functional probe. Thus many aspects of the biogeochemical cycle of selenium remains to be explored.

Single and Combined Impacts of Vitamin A and Selenium in Diet on Productive Performance, Egg Quality, and Some Blood Parameters of Laying Hens During Hot Season.

PubMed

Abd El-Hack, Mohamed E; Mahrose, Khalid; Askar, Ali A; Alagawany, Mahmoud; Arif, Muhammad; Saeed, Muhammad; Abbasi, Farzana; Soomro, Rab Nawaz; Siyal, Farman Ali; Chaudhry, Maria Tabassum

2017-05-01

A study was conducted using 162 Bovans laying hens to investigate the impacts of extra dietary vitamin A (0, 8000, 16,000 IU/kg), selenium (0, 0.25, 0.50 mg/kg), and their combinations on the performance, egg quality, and blood biological parameters of laying hens during summer months. Supplemental vitamin A up to 16,000 IU/kg diet significantly (P < 0.05) improved all productive traits studied except feed intake which increased with 8000 IU/kg diet compared with control. Feed intake and feed conversion of hens fed diet supplemented with selenium revealed high statistical (P = 0.001) differences. All egg quality criteria were not significantly (P < 0.05) affected by dietary vitamin A except albumin percentage and Haugh units, since Haugh unit score was gradually increased with increasing vitamin A level. Vitamin A-enriched groups showed significant (P < 0.05 and 0.01) decreases in plasma albumen, total lipids, and total cholesterol in respect to the unsupplemented groups. Compared with unsupplemented groups, total protein, albumin, total lipid, and total cholesterol were increased in selenium-enriched groups. There were no significant impacts of selenium treatments in layer diets on thyroid hormones and liver enzymes studied except alanine transferase (ALT) and thyroxin (T 4 ), as compared with the control group. Hematological parameters were not affected by vitamin A treatment except PCV% which decreased with vitamin A supplementation. Hemoglobin and lymphocytes were increased with increasing dietary selenium level. In conclusion, the combined supplementary concentrations of vitamin A (16,000 IU/kg) and selenium (0.25 mg/kg) might be needed for better production and health of laying hens reared under heat stress conditions.

Association between serum selenium level and conversion of bacteriological tests during antituberculosis treatment* **

PubMed Central

de Moraes, Milena Lima; Ramalho, Daniela Maria de Paula; Delogo, Karina Neves; Miranda, Pryscila Fernandes Campino; Mesquita, Eliene Denites Duarte; de Oliveira, Hedi Marinho de Melo Guedes; Ruffino-Netto, Antônio; de Almeida, Paulo César; Hauser-Davis, Rachel Ann; Campos, Reinaldo Calixto; Kritski, Afrânio Lineu; de Oliveira, Martha Maria

2014-01-01

Objective: To determine whether serum selenium levels are associated with the conversion of bacteriological tests in patients diagnosed with active pulmonary tuberculosis after eight weeks of standard treatment. Methods: We evaluated 35 healthy male controls and 35 male patients with pulmonary tuberculosis, the latter being evaluated at baseline, as well as at 30 and 60 days of antituberculosis treatment. For all participants, we measured anthropometric indices, as well as determining serum levels of albumin, C-reactive protein (CRP) and selenium. Because there are no reference values for the Brazilian population, we used the median of the serum selenium level of the controls as the cut-off point. At 30 and 60 days of antituberculosis treatment, we repeated the biochemical tests, as well as collecting sputum for smear microscopy and culture from the patients. Results: The mean age of the patients was 38.4 ± 11.4 years. Of the 35 patients, 25 (71%) described themselves as alcoholic; 20 (57.0%) were smokers; and 21 (60.0%) and 32 (91.4%) presented with muscle mass depletion as determined by measuring the triceps skinfold thickness and arm muscle area, respectively. Of 24 patients, 12 (39.2%) were classified as moderately or severely emaciated, and 15 (62.5%) had lost > 10% of their body weight by six months before diagnosis. At baseline, the tuberculosis group had lower serum selenium levels than did the control group. The conversion of bacteriological tests was associated with the CRP/albumin ratio and serum selenium levels 60 days after treatment initiation. Conclusions: Higher serum selenium levels after 60 days of treatment were associated with the conversion of bacteriological tests in pulmonary tuberculosis patients. PMID:25029650

Association between serum selenium level and conversion of bacteriological tests during antituberculosis treatment.

PubMed

Moraes, Milena Lima de; Ramalho, Daniela Maria de Paula; Delogo, Karina Neves; Miranda, Pryscila Fernandes Campino; Mesquita, Eliene Denites Duarte; Oliveira, Hedi Marinho de Melo Guedes de; Ruffino-Netto, Antônio; Almeida, Paulo César de; Hauser-Davis, Rachel Ann; Campos, Reinaldo Calixto; Kritski, Afrânio Lineu; Oliveira, Martha Maria de

2014-01-01

To determine whether serum selenium levels are associated with the conversion of bacteriological tests in patients diagnosed with active pulmonary tuberculosis after eight weeks of standard treatment. We evaluated 35 healthy male controls and 35 male patients with pulmonary tuberculosis, the latter being evaluated at baseline, as well as at 30 and 60 days of antituberculosis treatment. For all participants, we measured anthropometric indices, as well as determining serum levels of albumin, C-reactive protein (CRP) and selenium. Because there are no reference values for the Brazilian population, we used the median of the serum selenium level of the controls as the cut-off point. At 30 and 60 days of antituberculosis treatment, we repeated the biochemical tests, as well as collecting sputum for smear microscopy and culture from the patients. The mean age of the patients was 38.4 ± 11.4 years. Of the 35 patients, 25 (71%) described themselves as alcoholic; 20 (57.0%) were smokers; and 21 (60.0%) and 32 (91.4%) presented with muscle mass depletion as determined by measuring the triceps skinfold thickness and arm muscle area, respectively. Of 24 patients, 12 (39.2%) were classified as moderately or severely emaciated, and 15 (62.5%) had lost > 10% of their body weight by six months before diagnosis. At baseline, the tuberculosis group had lower serum selenium levels than did the control group. The conversion of bacteriological tests was associated with the CRP/albumin ratio and serum selenium levels 60 days after treatment initiation. Higher serum selenium levels after 60 days of treatment were associated with the conversion of bacteriological tests in pulmonary tuberculosis patients.

Selenocysteine in proteins-properties and biotechnological use.

PubMed

Johansson, Linda; Gafvelin, Guro; Arnér, Elias S J

2005-10-30

Selenocysteine (Sec), the 21st amino acid, exists naturally in all kingdoms of life as the defining entity of selenoproteins. Sec is a cysteine (Cys) residue analogue with a selenium-containing selenol group in place of the sulfur-containing thiol group in Cys. The selenium atom gives Sec quite different properties from Cys. The most obvious difference is the lower pK(a) of Sec, and Sec is also a stronger nucleophile than Cys. Proteins naturally containing Sec are often enzymes, employing the reactivity of the Sec residue during the catalytic cycle and therefore Sec is normally essential for their catalytic efficiencies. Other unique features of Sec, not shared by any of the other 20 common amino acids, derive from the atomic weight and chemical properties of selenium and the particular occurrence and properties of its stable and radioactive isotopes. Sec is, moreover, incorporated into proteins by an expansion of the genetic code as the translation of selenoproteins involves the decoding of a UGA codon, otherwise being a termination codon. In this review, we will describe the different unique properties of Sec and we will discuss the prerequisites for selenoprotein production as well as the possible use of Sec introduction into proteins for biotechnological applications. These include residue-specific radiolabeling with gamma or positron emitters, the use of Sec as a reactive handle for electophilic probes introducing fluorescence or other peptide conjugates, as the basis for affinity purification of recombinant proteins, the trapping of folding intermediates, improved phasing in X-ray crystallography, introduction of 77Se for NMR spectroscopy, or, finally, the analysis or tailoring of enzymatic reactions involving thiol or oxidoreductase (redox) selenolate chemistry.

Selenium nanoparticles involve HSP-70 and SIRT1 in preventing the progression of type 1 diabetic nephropathy.

PubMed

Kumar, Goru Santosh; Kulkarni, Apoorva; Khurana, Amit; Kaur, Jasmine; Tikoo, Kulbhushan

2014-11-05

The present study was undertaken to examine the protective effect of selenium nanoparticles (SeNPs) in the progression of diabetic nephropathy (DN). Diabetes was induced in male Sprague Dawley (SD) rats by injecting streptozotocin (STZ) (55mg/kg, i.p). DN was then assessed by measuring blood urea nitrogen (BUN), creatinine, albumin, fibronectin and collagen. Changes in the expression of cytoprotective and apoptotic proteins in the kidney of rats were also examined. Herein we show that SeNPs effectively lowered the levels of BUN, creatinine, fibronectin and collagen and elevated the levels of albumin in diabetic rats. Histological observation corroborated with the above protective effects of SeNPs. Interestingly, SeNPs elevated the levels of heat shock protein (HSP-70), longevity protein SIRT 1 and also modulated apoptotic proteins Bax and Bcl-2 in diabetic kidney. Our data represents a paradigm shift in our understanding about the therapeutic potential of SeNPs in preventing DN by not only quenching oxidative stress but also by activating cyto-protective protein HSP70 and longevity protein SIRT1. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Hypolipidemic and Pleiotropic Effects of Rosuvastatin Are Not Enhanced by Its Association with Zinc and Selenium Supplementation in Coronary Artery Disease Patients: A Double Blind Randomized Controlled Study

PubMed Central

Sena-Evangelista, Karine Cavalcanti Maurício; Pedrosa, Lucia Fatima Campos; Paiva, Maria Sanali Moura Oliveira; Dias, Paula Cristina Silveira; Ferreira, Diana Quitéria Cabral; Cozzolino, Sílvia Maria Franciscato; Faulin, Tanize Espírito Santo; Abdalla, Dulcinéia Saes Parra

2015-01-01

Objective Statins treatment may modify the levels of zinc and selenium, minerals that can improve vascular function and reduce oxidative damage and inflammation in atherosclerotic patients. This study aimed to evaluate the effects of rosuvastatin, alone or associated with zinc and selenium supplementation, on lipid profile, antioxidant enzymes and mineral status in coronary artery disease patients. Material and Methods A double-blind randomized clinical trial was performed in which patients (n = 76) were treated with 10 mg rosuvastatin over 4 months associated or not with zinc (30 mg/d) and selenium (150 μg/d) supplementation. The following parameters were analyzed before and after the intervention: anthropometric measurements, lipid profile, high sensitivity C-reactive protein (hs-CRP), electronegative low density lipoprotein (LDL(-)) concentrations, activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), zinc and selenium concentrations in blood plasma and erythocytes. Significance was determined using an α of 5% (two-tailed). Results We found that rosuvastatin therapy was efficient in reducing total cholesterol, LDL-cholesterol, non-HDL cholesterol, triglycerides, and hs-CRP independently of mineral supplementation. Neither treatment was associated with significant changes in LDL(-). Similarly, the antioxidant enzymes GPx and SOD activity were unchanged by treatments. Neither treatment was associated with significant differences in concentrations of zinc or selenium in blood plasma and erythocytes of studied groups. Conclusion Rosuvastatin treatment did not affect zinc and selenium levels in coronary artery disease patients. The zinc and selenium supplementation at doses used in this study did not change lipid profile or SOD and GPx activity in patients receiving rosuvastatin. Further studies should be focused on testing alternative doses and supplements in different populations to contribute for a consensus on the ideal choice of antioxidants to be used as possible complementary therapies in atherosclerotic patients. Trial Registration ClinicalTrials.gov NCT01547377 PMID:25785441

Whey Protein

MedlinePlus

... infections as taking a combination of zinc, selenium, glutamine, and metoclopramide. Muscular disease (mitochondrial myopathies). Early research ... or 42-84 grams per day in a glutamine-enriched formula. For red, scaly skin (plaque psoriasis): ...

Selenium-Dependent Antioxidant Enzymes: Actions and Properties of Selenoproteins

PubMed Central

Zoidis, Evangelos; Seremelis, Isidoros; Kontopoulos, Nikolaos

2018-01-01

Unlike other essential trace elements that interact with proteins in the form of cofactors, selenium (Se) becomes co-translationally incorporated into the polypeptide chain as part of 21st naturally occurring amino acid, selenocysteine (Sec), encoded by the UGA codon. Any protein that includes Sec in its polypeptide chain is defined as selenoprotein. Members of the selenoproteins family exert various functions and their synthesis depends on specific cofactors and on dietary Se. The Se intake in productive animals such as chickens affect nutrient utilization, production performances, antioxidative status and responses of the immune system. Although several functions of selenoproteins are unknown, many disorders are related to alterations in selenoprotein expression or activity. Selenium insufficiency and polymorphisms or mutations in selenoproteins’ genes and synthesis cofactors are involved in the pathophysiology of many diseases, including cardiovascular disorders, immune dysfunctions, cancer, muscle and bone disorders, endocrine functions and neurological disorders. Finally, heavy metal poisoning decreases mRNA levels of selenoproteins and increases mRNA levels of inflammatory factors, underlying the antagonistic effect of Se. This review is an update on Se dependent antioxidant enzymes, presenting the current state of the art and is focusing on results obtained mainly in chicken. PMID:29758013

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

PubMed Central

2012-01-01

Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC. PMID:22726388

Assessment and characterisation of yeast-based products intended to mitigate ochratoxin exposure using in vitro and in vivo models.

PubMed

Pfohl-Leszkowicz, A; Hadjeba-Medjdoub, K; Ballet, N; Schrickx, J; Fink-Gremmels, J

2015-01-01

The aim of this paper was to evaluate the capacity of several yeast-based products, derived from baker's and brewer's yeasts, to sequester the mycotoxin ochratoxin A (OTA) and to decrease its rate of absorption and DNA adduct formation in vivo. The experimental protocol included in vitro binding studies using isotherm models, in vivo chicken experiments, in which the serum and tissue concentrations of OTA were analysed in the absence and presence of the test compounds, and the profile of OTA-derived metabolites and their associated DNA adducts were determined. Additionally in vitro cell culture studies (HK2 cells) were applied to assess further the effects for yeast cell product enriched with glutathione (GSH) or selenium. Results of the in vitro binding assay in a buffer system indicated the ability of the yeast-based products, as sequester of OTA, albeit at a different level. In the in vitro experiments in chickens, decreased serum and tissue concentrations of treated animals confirmed that yeast-based products are able to prevent the absorption of OTA. A comparison of the binding affinity in a standard in vitro binding assay with the results obtained in an in vivo chicken experiment, however, showed a poor correlation and resulted in a different ranking of the products. More importantly, we could show that yeast-based products actively modulate the biotransformation of OTA in vivo as well as in vitro in a cell culture model. This effect seems to be attributable to residual enzymatic activities in the yeast-based products. An enrichment of yeast cell wall products with GSH or selenium further modulated the profile of the generated OTA metabolites and the associated pattern of OTA-induced DNA adducts by increasing the conversion of OTA into less toxic metabolites such as OTA, OTB and 4-OH-OTA. A reduced absorption and DNA adduct formation was particularly observed with GSH-enriched yeast, whereas selenium-enriched yeasts could counteract the OTA-induced decrease in cell viability, but at the same time increased the OTA-DNA adducts formation. These findings indicate the need for an in-depth characterisation of yeast-based products used as mycotoxin-mitigating feed additives, in in vivo models with target animal species taking into account not only their ability to sequester toxins in the gastrointestinal tract but also their potential effects on the biotransformation of mycotoxins.

JV Task 77 - Health Implications of Mercury - Selenium Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas Ralstion; Laura Raymond

2007-12-15

Exposure to mercury (Hg) commonly results from eating fish containing bioaccumulated methylmercury (MeHg). However, conflicting observations and conclusions have arisen from the ongoing human studies of MeHg exposure from fish consumption. Resolving these uncertainties has important implications for human health since significant nutritional benefits will be lost if fish consumption is needlessly avoided. Selenium (Se), an important nutrient that is abundant in ocean fish, has a potent protective effect against Hg toxicity. This protective effect was thought to be due to the high binding affinities between Hg and Se resulting in Se sequestration of Hg to prevent its harmful effects.more » However, it is imperative to consider the opposing effect of Hg on Se physiology. Crucial proteins that require Se normally protect the brain and hormone-producing glands from oxidative damage. MeHg is able to cross all biological barriers and enter cells in these tissues, where its high Se affinity results in Se sequestration. Sequestration in association with Hg prevents Se from participating in proteins that perform essential antioxidant activities. Supplemental dietary Se is able to replace Se sequestered by Hg and maintain normal antioxidant protection of brain and glands. The goal of this research project was to assess the potency of normal dietary levels of Se in protection against MeHg toxicity. Results from this project indicate that MeHg toxicity is only evident in situations resulting in Hg occurring in high molar excess of Se. Additionally, the common method of MeHg risk assessments using measurements of toenail and blood levels of Hg was shown to provide an accurate reflection of Hg exposure but did not accurately indicate risk of toxicity resulting from that exposure. Instead, Hg:Se molar ratios are proposed as a superior means of assessing risks associated with MeHg exposure.« less

Molecular consequences of genetic variations in the glutathione peroxidase 1 selenoenzyme.

PubMed

Zhuo, Pin; Goldberg, Marci; Herman, Lauren; Lee, Bao-Shiang; Wang, Hengbing; Brown, Rhonda L; Foster, Charles B; Peters, Ulrike; Diamond, Alan M

2009-10-15

Accumulating data have implicated the selenium-containing cytosolic glutathione peroxidase, GPx-1, as a determinant of cancer risk and a mediator of the chemopreventive properties of selenium. Genetic variants of GPx-1 have been shown to be associated with cancer risk for several types of malignancies. To investigate the relationship between GPx-1 enzyme activity and genotype, we measured GPx-1 enzyme activity and protein levels in human lymphocytes as a function of the presence of two common variations: a leucine/proline polymorphism at codon 198 and a variable number of alanine-repeat codons. Differences in GPx activity among these cell lines, as well as in the response to the low-level supplementation of the media with selenium, indicated that factors other than just genotype are significant in determining activity. To restrict the study to genotypic effects, human MCF-7 cells were engineered to exclusively express allelic variants representing a combination of either a codon 198 leucine or proline and either 5 or 7 alanine-repeat codons following transfection of GPx-1 expression constructs. Transfectants were selected and analyzed for GPx-1 enzyme activity and protein levels. GPx-1 with 5 alanines and a leucine at codon 198 showed a significantly higher induction when cells were incubated with selenium and showed a distinct pattern of thermal denaturation as compared with GPx-1 encoded by the other examined alleles. The collective data obtained using both lymphocytes and MCF-7 indicate that both intrinsic and extrinsic factors cooperate to ultimately determine the levels of this enzyme available to protect cells against DNA damage and mutagenesis.

Selenium. Role of the Essential Metalloid in Health

PubMed Central

Kurokawa, Suguru; Berry, Marla J.

2015-01-01

Selenium is an essential micronutrient in mammals, but is also recognized as toxic in excess. It is a non-metal with properties that are intermediate between the chalcogen elements sulfur and tellurium. Selenium exerts its biological functions through selenoproteins. Selenoproteins contain selenium in the form of the 21st amino acid, selenocysteine (Sec), which is an analog of cysteine with the sulfur-containing side chain replaced by a Se-containing side chain. Sec is encoded by the codon UGA, which is one of three termination codons for mRNA translation in non-selenoprotein genes. Recognition of the UGA codon as a Sec insertion site instead of stop requires a Sec insertion sequence (SECIS) element in selenoprotein mRNAs and a unique selenocysteyl-tRNA, both of which are recognized by specialized protein factors. Unlike the 20 standard amino acids, Sec is biosynthesized from serine on its tRNA. Twenty-five selenoproteins are encoded in the human genome. Most of the selenoprotein genes were discovered by bioinformatics approaches, searching for SECIS elements downstream of in-frame UGA codons. Sec has been described as having stronger nucleophilic and electrophilic properties than cysteine, and Sec is present in the catalytic site of all selenoenzymes. Most selenoproteins, whose functions are known, are involved in redox systems and signaling pathways. However, several selenoproteins are not well characterized in terms of their function. The selenium field has grown dramatically in the last few decades, and research on selenium biology is providing extensive new information regarding its importance for human health. PMID:24470102

Kinetic consequences of introducing a proximal selenocysteine ligand into cytochrome P450cam.

PubMed

Vandemeulebroucke, An; Aldag, Caroline; Stiebritz, Martin T; Reiher, Markus; Hilvert, Donald

2015-11-10

The structural, electronic, and catalytic properties of cytochrome P450cam are subtly altered when the cysteine that coordinates to the heme iron is replaced with a selenocysteine. To map the effects of the sulfur-to-selenium substitution on the individual steps of the catalytic cycle, we conducted a comparative kinetic analysis of the selenoenzyme and its cysteine counterpart. Our results show that the more electron-donating selenolate ligand has only negligible effects on substrate, product, and oxygen binding, electron transfer, catalytic turnover, and coupling efficiency. Off-pathway reduction of oxygen to give superoxide is the only step significantly affected by the mutation. Incorporation of selenium accelerates this uncoupling reaction approximately 50-fold compared to sulfur, but because the second electron transfer step is much faster, the impact on overall catalytic turnover is minimal. Density functional theory calculations with pure and hybrid functionals suggest that superoxide formation is governed by a delicate interplay of spin distribution, spin state, and structural effects. In light of the remarkably similar electronic structures and energies calculated for the sulfur- and selenium-containing enzymes, the ability of the heavier atom to enhance the rate of spin crossover may account for the experimental observations. Because the selenoenzyme closely mimics wild-type P450cam, even at the level of individual steps in the reaction cycle, selenium represents a unique mechanistic probe for analyzing the role of the proximal ligand and spin crossovers in P450 chemistry.

Biomimetic synthesis of selenium nanoparticles by Pseudomonas aeruginosa ATCC 27853: An approach for conversion of selenite.

PubMed

Kora, Aruna Jyothi; Rastogi, Lori

2016-10-01

A facile and green method for the reduction of selenite was developed using a Gram-negative bacterial strain Pseudomonas aeruginosa, under aerobic conditions. During the process of bacterial conversion, the elemental selenium nanoparticles were produced. These nanoparticles were systematically characterized using various analytical techniques including UV-visible spectroscopy, XRD, Raman spectroscopy, SEM, DLS, TEM and FTIR spectroscopy techniques. The generation of selenium nanoparticles was confirmed from the appearance of red colour in the culture broth and broad absorption peaks in the UV-vis. The synthesized nanoparticles were spherical, polydisperse, ranged from 47 to 165 nm and the average particle size was about 95.9 nm. The selected-area electron diffraction, XRD patterns; and Raman spectroscopy established the amorphous nature of the fabricated nanoparticles. The IR data demonstrated the bacterial protein mediated selenite reduction and capping of the produced nanoparticles. The selenium removal was assessed at different selenite concentrations using ICP-OES and the results showed that the tested bacterial strain exhibited significant selenite reduction activity. The results demonstrate the possible application of P. aeruginosa for bioremediation of waters polluted with toxic and soluble selenite. Moreover, the potential metal reduction capability of the bacterial strain can function as green method for aerobic generation of selenium nanospheres. Copyright © 2016 Elsevier Ltd. All rights reserved.

Six independent fucose-binding sites in the crystal structure of Aspergillus oryzae lectin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makyio, Hisayoshi; Shimabukuro, Junpei; Suzuki, Tatsuya

The crystal structure of AOL (a fucose-specific lectin of Aspergillus oryzae) has been solved by SAD (single-wavelength anomalous diffraction) and MAD (multi-wavelength anomalous diffraction) phasing of seleno-fucosides. The overall structure is a six-bladed β-propeller similar to that of other fucose-specific lectins. The fucose moieties of the seleno-fucosides are located in six fucose-binding sites. Although the Arg and Glu/Gln residues bound to the fucose moiety are common to all fucose-binding sites, the amino-acid residues involved in fucose binding at each site are not identical. The varying peak heights of the seleniums in the electron density map suggest that each fucose-binding sitemore » has a different carbohydrate binding affinity. - Highlights: • The six-bladed β-propeller structure of AOL was solved by seleno-sugar phasing. • The mode of fucose binding is essentially conserved at all six binding sites. • The seleno-fucosides exhibit slightly different interactions and electron densities. • These findings suggest that the affinity for fucose is not identical at each site.« less

Selenomethionine ameliorates cognitive decline, reduces tau hyperphosphorylation, and reverses synaptic deficit in the triple transgenic mouse model of Alzheimer's disease.

PubMed

Song, Guoli; Zhang, Zhonghao; Wen, Lei; Chen, Chen; Shi, Qingxue; Zhang, Yu; Ni, Jiazuan; Liu, Qiong

2014-01-01

Disruption of the intracellular balance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of Alzheimer's disease (AD). Selenium, a vital trace element with known antioxidant potential, has been reported to provide neuroprotection through resisting oxidative damage but its therapeutic effect on AD remains to be investigated. The objective of our study was to investigate the potential of selenomethionine (Se-Met), an organic form of selenium, in the treatment of cognitive dysfunction and neuropathology of triple transgenic AD (3 × Tg-AD) mice. 3 × Tg-AD mice, which were four months old, were treated with Se-Met for 3 months and demonstrated significant improvements in cognitive deficit along with an increased selenium level compared with the untreated control mice. Se-Met treatment significantly reduced the level of total tau and phosphorylated tau, mitigated the decrease of synaptic proteins including synaptophysin and postsynaptic density protein 95 in the hippocampus and cortex of the 3 × Tg-AD mice. Meanwhile, glial activation in AD mice was inhibited and the level of reduced glutathione was increased in the treated mice compared with control mice. Additionally, the expression and activity of glycogen synthase kinase 3β and protein phosphatase 2A, two important enzymes involved in tau phosphorylation, were markedly decreased and increased respectively by Se-Met treatment. Thus Se-Met improves cognitive deficit in a murine model of AD, which is associated with reduction in tau expression and hyperphosphorylation, amelioration of inflammation, and restoration of synaptic proteins and antioxidants. This study provides a novel therapeutic approach for the prevention of AD.

Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA.

PubMed

Carlson, Bradley A; Xu, Xue-Ming; Gladyshev, Vadim N; Hatfield, Dolph L

2005-02-18

Selenocysteine (Sec) is the 21st amino acid in the genetic code. Its tRNA is variably methylated on the 2'-O-hydroxyl site of the ribosyl moiety at position 34 (Um34). Herein, we identified a role of Um34 in regulating the expression of some, but not all, selenoproteins. A strain of knock-out transgenic mice was generated, wherein the Sec tRNA gene was replaced with either wild type or mutant Sec tRNA transgenes. The mutant transgene yielded a tRNA that lacked two base modifications, N(6)-isopentenyladenosine at position 37 (i(6)A37) and Um34. Several selenoproteins, including glutathione peroxidases 1 and 3, SelR, and SelT, were not detected in mice rescued with the mutant transgene, whereas other selenoproteins, including thioredoxin reductases 1 and 3 and glutathione peroxidase 4, were expressed in normal or reduced levels. Northern blot analysis suggested that other selenoproteins (e.g. SelW) were also poorly expressed. This novel regulation of protein expression occurred at the level of translation and manifested a tissue-specific pattern. The available data suggest that the Um34 modification has greater influence than the i(6)A37 modification in regulating the expression of various mammalian selenoproteins and Um34 is required for synthesis of several members of this protein class. Many proteins that were poorly rescued appear to be involved in responses to stress, and their expression is also highly dependent on selenium in the diet. Furthermore, their mRNA levels are regulated by selenium and are subject to nonsense-mediated decay. Overall, this study described a novel mechanism of regulation of protein expression by tRNA modification that is in turn regulated by levels of the trace element, selenium.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 3. Serum chemistry and fish health indicators.

PubMed

Lohner, T W; Reash, R J; Willet, V E; Fletcher, J

2001-11-01

Sunfish were collected from fly ash discharge-receiving streams to assess the possible effects of exposure to elevated selenium. Concentrations of selenium, copper, and arsenic were statistically higher in fish tissue (liver) samples from effluent-exposed fish than in reference fish. Several biomarkers were indicative of metal exposure and effect. Plasma protein levels and cholesterol levels were significantly lower in exposed fish, indicating nutritional stress. Ion levels (i.e., K) increased with exposure to ash pond metals, indicating possible gill damage. Fish from the receiving streams also had increased serum glucose and osmolality indicating possible acute stress due to sampling. Fish health assessments revealed a lower incidence of fin erosion, kidney discoloration, urolithiasis or nephrocalcinosis, liver discoloration, and parasites in exposed fish and a higher incidence of skin, eye, and gill aberrations. Condition factors of exposed fish were correlated with biomarker response and were the same as or lower than those of reference fish, but not related to selenium levels. Although several serum biochemical indicators differed between the ash pond-receiving stream and reference sites, pollutant exposure was apparently not sufficient to cause functional damage to critical organ systems.

Selenium and Iron Oxide Nanocomposites for Magnetically-Targeted Anti-Cancer Applications.

PubMed

Hauksdóttir, Halla Laufey; Webster, Thomas J

2018-03-01

Iron oxide nanoparticles (IONP) are already well-established in the medical field due to their ability to improve contrast in magnetic resonance imaging (MRI) and for their external magnetic control in the body. Moreover, selenium has been shown to kill numerous cancer cells at lower concentrations that IONP (e.g., 1 μg/ml). Selenium is a trace mineral of growing interest in cancer treatment since it is an essential nutrient in the human body and can interfere with thiolcontaining proteins necessary for cancer cells to function. For the above reasons, the goal of this in vitro study was to combine the above chemistries for the first time to develop composite nano-vehicles for magnetically targeted cancer therapy. The suggested design was an IONP core, stabilized by chitosan and decorated with selenium. Two different types of IONP cores were produced. This was followed by different chitosan and selenium coating methods. The particles were characterized for size, shape, zeta potential and magnetic properties. Finally, the most promising products were tested for cancer killing properties on MB-231 breast cancer cells. Results of this pioneering study showed that the most promising iron-selenium nanocomposites consisted of an iron oxide core produced by thermal decomposition, followed by a silane ligand exchange, a chitosan coating and selenium decoration. The particles were 5-9 nm in diameter, with a zeta potential of 29.59 mV and magnetic properties of 35.932 emu/g. Moreover, the novel nanoparticles had concentration dependent cancer killing properties. Specifically, after just 1 day of incubation, breast cancer cell viability was reduced to 40.5% in the presence of 1 μg/ml of these composite nanoparticles (and statistically reduced at even 0.1 μg/ml), without using a chemotherapeutic pharmaceutical drug. This is a significant finding since neither chemotherapeutic pharmaceutical drugs, infrared stimulation, nor magnetism were used. In this manner, this study introduces a brand new composite nanoparticle consisting of iron oxide and selenium which should be further studied for a wide range of magnetically targeted anticancer applications.

Effects of selenium supplementation on the oxidative state of acute heat stress-exposed quails.

PubMed

Del Vesco, A P; Gasparino, E; Zancanela, V; Grieser, D O; Stanquevis, C E; Pozza, P C; Oliveira Neto, A R

2017-02-01

This study aimed to evaluate the effect of heat stress (HS) and selenium supplementation on markers of stress, meat quality and gene expression. For this, meat quails of 42 days of age were fed a diet that either met [0.33 mg/kg, nutritional demand for selenium (SS)] or did not meet [0.11 mg/kg, selenium deficient (SD)] the nutritional demands for selenium during the 7 days of evaluation. In addition, the animals were kept at either a thermal comfort temperature (25 °C) or exposed to HS (38 °C for 24 h). Glutathione synthetase (GSS), glutathione reductase (GSR) and uncoupling protein (UCP) gene expression were influenced by the interaction between temperature and diet. Animals subjected to HS and fed the SS diet exhibited the highest GSS and GSR gene expression. In terms of UCP gene expression, the lowest values were observed in HS animals on the SD diet. Glutathione peroxidase 7 (GPX7) gene expression, body temperature (BT) and creatine kinase (CK) activity were influenced by both selenium supplementation and HS. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and creatinine content all were influenced by the diet/environment interaction. The highest AST activity, ALT activity and creatinine levels were observed in animals that were both on the SD diet and exposed to HS. HS animals also exhibited an increased heterophil/lymphocyte ratio and lower triiodothyronine (T3) hormone levels than birds that remained at the comfortable temperature. Animals subjected to HS and fed with selenium supplemented diet showed better results regarding gene expression and, thus, better results for the activities of enzymes used as stress markers, which could be due to the higher antioxidant capacity provided by the action of the studied genes. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial.

PubMed

Asemi, Zatollah; Jamilian, Mehri; Mesdaghinia, Elaheh; Esmaillzadeh, Ahmad

2015-10-01

To our knowledge, no reports are available indicating the effects of selenium supplementation on metabolic parameters, inflammatory factors, and oxidative stress in gestational diabetes mellitus (GDM). The aim of this study was to assess the effects of selenium supplementation on metabolic status in pregnant women with GDM who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was performed with 70 women with GDM. Patients were randomly assigned to receive either 200 μg selenium supplements as tablet (n = 35) or placebo (n = 35) for 6 wk from weeks 24 to 28 of gestation. Fasting plasma samples were taken at study baseline and after 6 wk of intervention to quantify related variables. Selenium supplementation, compared with placebo, resulted in a significant reduction in fasting plasma glucose (-10.5 ± 11.9 versus +4.5 ± 12.9 mg/dL; P < 0.001), serum insulin levels (-1.98 ± 11.25 versus +5.26 ± 9.33 μIU/mL; P = 0.005), homeostasis model of assessment (HOMA)-insulin resistance (-0.84 ± 2.76 versus +1.47 ± 2.46; P < 0.001) and a significant increase in quantitative insulin sensitivity check index (+0.008 ± 0.03 versus -0.01 ± 0.01; P = 0.009). Additionally, a significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) levels (-791.8 ± 2271.8 versus +500.5 ± 2563.3 ng/mL; P = 0.02) was seen after the administration of selenium supplements compared with placebo. Additionally, we observed a significant elevation in plasma glutathione (+52.14 ± 58.31 versus -39.93 ± 153.52 μmol/L; P = 0.002) and a significant reduction in plasma malondialdehyde levels (-0.01 ± 0.36 versus +0.67 ± 1.90 μmol/L; P = 0.04) after consumption of selenium supplements compared with placebo. We did not find any significant effect of taking selenium supplements on HOMA β-cell function, lipid profiles, plasma nitric oxide, or total antioxidant capacity concentrations. Selenium supplementation in pregnant women with GDM demonstrated beneficial effects on glucose metabolism, hs-CRP levels, and biomarkers of oxidative stress. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary Selenium Deficiency or Excess Reduces Sperm Quality and Testicular mRNA Abundance of Nuclear Glutathione Peroxidase 4 in Rats.

PubMed

Zhou, Ji-Chang; Zheng, Shijie; Mo, Junluan; Liang, Xiongshun; Xu, Yuanfei; Zhang, Huimin; Gong, Chunmei; Liu, Xiao-Li; Lei, Xin Gen

2017-10-01

Background: Glutathione peroxidase (GPX) 4 and selenoprotein P (SELENOP) are abundant, and several variants are expressed in the testis. Objective: We determined the effects of dietary selenium deficiency or excess on sperm quality and expressions of GPX4 and SELENOP variants in rat testis and liver. Methods: After weaning, male Sprague-Dawley rats were fed a Se-deficient basal diet (BD) for 5 wk until they were 9 wk old [mean ± SEM body weight (BW) = 256 ± 5 g]. They were then fed the BD diet alone (deficient) or with 0.25 (adequate), 3 (excess), or 5 (excess) mg Se/kg for 4 wk. Testis, liver, blood, and semen were collected to assay for selenoprotein mRNA and protein abundances, selenium concentration, GPX activity, 8-hydroxy-deoxyguanosine concentration, and sperm quality. Results: Dietary selenium supplementations elevated ( P < 0.05) tissue selenium concentrations and GPX activities. Compared with those fed BD + 0.25 mg Se/kg, rats fed BD showed lower ( P < 0.05) BW gain (86%) and sperm density (57%) but higher ( P < 0.05) plasma 8-hydroxy-deoxyguanosine concentrations (189%), and nonprogressive sperm motility (4.4-fold). Likewise, rats fed BD + 5 mg Se/kg had ( P = 0.06) lower BW gain and higher (1.9-fold) sperm deformity rates than those in the selenium-adequate group. Compared with the selenium-adequate group, dietary selenium deficiency (BD) or excess (BD + 3 or 5 mg Se/kg) resulted in 45-77% lower ( P < 0.05) nuclear Gpx4 ( nGpx4 ) mRNA abundance in the testis. Rats fed BD had lower ( P < 0.05) mRNA levels of 2 Selenop variants in both testis and liver than those in the other groups. Testicular SELENOP was 155-170% higher ( P < 0.05) in rats fed BD + 5 mg Se/kg and hepatic c/mGPX4 was 13-15% lower ( P < 0.05) in rats fed BD than in the other groups. Conclusions: The mRNA abundance of rat testicular nGPX4 responded to dietary selenium concentrations in similar ways to sperm parameters and may be used as a sensitive marker to assess appropriate Se status for male function. © 2017 American Society for Nutrition.

Variation in Sulfur and Selenium Accumulation Is Controlled by Naturally Occurring Isoforms of the Key Sulfur Assimilation Enzyme ADENOSINE 5′-PHOSPHOSULFATE REDUCTASE2 across the Arabidopsis Species Range1[W][OPEN

PubMed Central

Chao, Dai-Yin; Baraniecka, Patrycja; Danku, John; Koprivova, Anna; Lahner, Brett; Luo, Hongbing; Yakubova, Elena; Dilkes, Brian; Kopriva, Stanislav; Salt, David E.

2014-01-01

Natural variation allows the investigation of both the fundamental functions of genes and their role in local adaptation. As one of the essential macronutrients, sulfur is vital for plant growth and development and also for crop yield and quality. Selenium and sulfur are assimilated by the same process, and although plants do not require selenium, plant-based selenium is an important source of this essential element for animals. Here, we report the use of linkage mapping in synthetic F2 populations and complementation to investigate the genetic architecture of variation in total leaf sulfur and selenium concentrations in a diverse set of Arabidopsis (Arabidopsis thaliana) accessions. We identify in accessions collected from Sweden and the Czech Republic two variants of the enzyme ADENOSINE 5′-PHOSPHOSULFATE REDUCTASE2 (APR2) with strongly diminished catalytic capacity. APR2 is a key enzyme in both sulfate and selenate reduction, and its reduced activity in the loss-of-function allele apr2-1 and the two Arabidopsis accessions Hodonín and Shahdara leads to a lowering of sulfur flux from sulfate into the reduced sulfur compounds, cysteine and glutathione, and into proteins, concomitant with an increase in the accumulation of sulfate in leaves. We conclude from our observation, and the previously identified weak allele of APR2 from the Shahdara accession collected in Tadjikistan, that the catalytic capacity of APR2 varies by 4 orders of magnitude across the Arabidopsis species range, driving significant differences in sulfur and selenium metabolism. The selective benefit, if any, of this large variation remains to be explored. PMID:25245030

Trace elements and their distribution in protein fractions of camel milk in comparison to other commonly consumed milks.

PubMed

Al-Awadi, F M; Srikumar, T S

2001-08-01

Studies on camels' milk, whether with respect to concentration or bioavailability of trace elements from this milk, are limited and warrant further investigation. The object of this study was to analyse the concentration and distribution of zinc, copper, selenium, manganese and iron in camel milk compared to those in human milk, cows' milk and infant formula under similar experimental conditions. Camels' milk and cows' milk were collected from local farms, human milk samples were obtained from healthy donors in Kuwait and infant formula was purchased locally. Milk fractionation was performed by ultra-centrifugation and gelcolumn chromatography. The concentration of trace elements was analysed by atomic absorption spectrometry and that of protein was determined spectrophotometrically. The concentration of manganese and iron in camels' milk was remarkably higher (7-20-fold and 4-10-fold, respectively) than in human milk, cows' milk and infant formula. The zinc content of camels' milk was higher than that of human milk but slightly lower than in cows' milk and infant formula. The concentration of copper in camels' milk was similar to that of cows' milk but lower than in human milk and infant formula. The selenium content of camels' milk was comparable to those of other types of milk, Approximately 50-80% of zinc, copper and manganese in camels' milk were associated with the casein fraction, similar to that of cows' milk, The majority of selenium and iron in camels' milk was in association with the low molecular weight fraction, It is recommended that camels' milk be considered as a potential source of manganese, selenium and iron, perhaps not only for infants, but also for other groups suspected of mild deficiency of these elements. Further investigations are required to confirm this proposal.

Hyperoxia, unlike phorbol ester, induces glutathione peroxidase through a protein kinase C-independent mechanism.

PubMed Central

Jornot, L; Junod, A F

1997-01-01

Human selenium-dependent glutathione peroxidase (GP) is implicated as a mechanism of resistance against oxygen free radicals. The 5' flanking sequence upstream from the coding region of GP contained an oxygen-responsive element termed ORE1 that is responsive to hypoxia, as well as several copies of the activator protein-1 (AP-1)- and AP-1-like-binding sites. In this study, we sought to define the molecular events that lead to GP gene transcription in response to hyperoxia in human umbilical-vein endothelial cells, and asked whether such induction is mimicked and sustained by activation of protein kinase C (PKC) by phorbol esters. Treatment of cells with 100 nM phorbol 12,13-dibutyrate (PdBu) induced a delayed (24-48 h) but significant (2-fold) increase in steady-state GP mRNA levels. Steady-state GP mRNA levels also rose after exposure to 95% O2, again after considerable delay (48-72 h). For both PdBu and oxygen, induction was transcriptionally regulated, as demonstrated by nuclear run-on experiments. The simulations by PdBu and oxygen were additive. In contrast with PdBu, hyperoxia did not stimulate translocation of PKC from the cytosol to the particulate fraction, although the specific activity of both cytosolic and particulate-associated PKC was increased 2-fold in cells exposed to 95% O2 for 5 days. In addition, gel mobility-shift assays using double-stranded tumour-promoting-agent-responsive element (TRE) and nuclear extracts derived from phorbol- and oxygen-treated cells revealed that PdBu, but not hyperoxia, increased AP-1 DNA-binding activity. On the other hand, the up-regulation of GP expression by oxygen could not be accounted for by the ORE1 core sequence, since no specific protein-DNA binding activity could be detected using nuclear extracts from hyperoxic cells and ORE1. Taken together, these results suggest that there may be different molecular mechanisms controlling GP expression. After exposure to PdBu, GP undergoes transcriptional activation via a process that can be readily explained by a classic AP-1 interaction with the TRE sites in the GP promoter. During hyperoxia, GP also undergoes transcriptional activity, but via a process that appears to involve neither TRE nor ORE1. PMID:9337858

Protective Role of Selenium Compounds on the Proliferation, Apoptosis, and Angiogenesis of a Canine Breast Cancer Cell Line.

PubMed

Liu, Yuzhi; Li, Wenyu; Guo, Mengyao; Li, Chengye; Qiu, Changwei

2016-01-01

We herein examined the effects of different doses, forms, and compatibilities of selenium on a canine mammary gland tumor cell line, CTM1211, and explored the related mechanisms. Three selenium compounds, sodium selenite (SSE), methylseleninic acid (MSA), and methylselenocysteine (MSC), were selected for these experiments, and cyclophosphamide (CTX) served as a positive control. In the cell viability assay, the cell viability of each group at 48/72 h decreased significantly compared with the control group (p < 0.05), and the cell viability of the CTX + MSA group was lower than that of CTX and MSA groups (p < 0.05). Moreover, the inhibitory effect of selenium on cell proliferation was time-dependent but not concentration-dependent. In the cell apoptosis assay, the apoptosis values of each group increased significantly compared with the control group, and the apoptosis values of the CTX + MSA group increased the most significantly (p < 0.01). The protein and mRNA expression levels of vascular endothelial growth factor-alpha (VEGF-alpha), angiopoietin-2 (Ang-2), and hypoxia inducible factor-1 alpha (HIF-1 alpha) were downregulated in each group, while that of phosphatase and tensin homolog (PTEN) were upregulated (p < 0.05). In conclusion, these three selenium compounds, especially MSA, could significantly inhibit the viability and growth of the CTM1211 cell line, which is partly due to the induction of apoptosis and regulation of tumor angiogenesis.

Toxicity and oxidative stress of different forms of organic selenium (Se) and dietary protein in mallard (Anas platyrhynchos) ducklings

USGS Publications Warehouse

Hoffman, D.; Heinz, G.; Eisemann, J.; Pendleton, G.

1994-01-01

High concentrations of Se have been found in aquatic food chains associated with irrigation drainwater and toxicity to fish and wildlife. Earlier studies have compared toxicities of Se as selenite and as seleno-DL-methionine (DL) in mallards. This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms. After 2 weeks blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L was the most toxic, resulting in high mortality (64%) and impaired growth (>50%) and the greatest increase in ratio of oxidized to reduced glutathione with 30 ppm in the diet. Se as Y accumulated the least in liver. In a subsequent experiment with 30% dietary protein Se as L was less toxic.

Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Jinsong; Wang Huali; Yu Hanqing

2007-10-01

Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes upmore » and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels.« less

Green synthesis of selenium nanoparticles conjugated Clausena dentata plant leaf extract and their insecticidal potential against mosquito vectors.

PubMed

Sowndarya, P; Ramkumar, G; Shivakumar, M S

2017-12-01

Mosquitoes are major vectors for the transmission of many diseases like chikungunya, malaria, dengue, zika, etc. worldwide. In the present study, selenium nanoparticles (SeNPs) were synthesized from Clausena dentata and were tested for their larvicidal efficacy against the fourth-instar larvae of Anopheles stephensi, Aedes Aegypti, and Culex quinquefasciatus. The synthesized nanoparticles were characterized using UV-Vis spectroscopy, Fourier Transform Infrared Radiation (FTIR) spectroscopy, EDaX, and SEM. The results recorded from UV-Vis spectroscopy show the peak absorption spectrum at 420 nm. In FTIR, the maximum peak value is 2922.25 cm -1 assigned to N-H group (amide group). In EDaX analysis shows peak around 72.64 which confirm the binding intensity of selenium. In SEM analysis, the synthesized SeNPs sizes were ranging from 46.32 nm to 78.88 nm. The synthesized SeNPs produced high mortality with very low concentration (LC 50 ) were 240.714 mg/L; 104.13 mg/L, and 99.602 mg/L for A. stephensi, A. Aegypti, and C. quinquefasciatus, respectively. These results suggest that the C. dentata leaf extract-mediated biosynthesis of SeNPs has the potential to be used as an ideal ecofriendly approach toward the control of mosquito vectors at early stages.

Physiological and proteomic analysis of selenium-mediated tolerance to Cd stress in cucumber (Cucumis sativus L.).

PubMed

Sun, Hongyan; Dai, Huaxin; Wang, Xiaoyun; Wang, Guohui

2016-11-01

Selenium can mitigate cadmium toxicity in plants. However, the mechanism of this alleviation has not been fully understood. In the present study, the role of Se in inducing tolerance to Cd stress in cucumber was elucidated. Results showed that Se significantly alleviated Cd-induced growth inhibition, reduced Cd concentration, increased SPAD value and improved photosynthetic performance. Through proteomic analysis by two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry, 26 protein spots were identified, which were significantly influenced by Cd stress and/or Se application. Among these proteins, the abundance of 21 spots (10 in leaves and 11 in roots) were repressed in Cd-treated and up-accumulated or no-changed in Cd+Se-treated cucumber. These altered proteins were involved in the response to stress, metabolism, photosynthesis and storage, they were including glutathione S-transferase F8, heat shock protein STI-like, peroxidase, ascorbate oxidase, fructose-bisphosphate aldolase 2, NiR, Rieske type ion sulfur subunit and PsbP domain-containing protein 6. Furthermore, we identified five proteins with an increase in relative abundance after Cd treatment, they were involved in the functional groups active in response to stress and transport. The present study provided novel insights into Se-mediated tolerance of cucumber seedlings against Cd toxicity at the proteome level. Copyright © 2016 Elsevier Inc. All rights reserved.

Biosynthesis of Se-methyl-seleno-l-cysteine in Basidiomycetes fungus Lentinula edodes (Berk.) Pegler.

PubMed

Klimaszewska, M; Górska, S; Dawidowski, M; Podsadni, P; Turło, J

2016-01-01

The aim of the current study was to investigate whether the Basidiomycetes fungus Lentinula edodes can biosynthesize Se-methyl-seleno-l-cysteine, a seleno-amino acid with strong anticancer activity, and to optimize the culture conditions for its biosynthesis. We hypothesize that preparations obtained from Se-methyl-seleno-l-cysteine-enriched mycelia from this medicinal mushroom would possess stronger cancer-preventive properties than current preparations. By optimizing the concentration of selenium in the culture medium, we increased the mycelial concentration of Se-methyl-seleno-l-cysteine from essentially non-detectable levels to 120 µg/g dry weight. Significantly elevated levels of this amino acid also correlated with significant (twofold) inhibition of mycelial growth. Increases in the concentration of mycelial Se-methyl-seleno-l-cysteine appeared to be highly correlated with the enhanced biosynthesis of selenomethionine and total selenium content in mycelium. We have demonstrated that in L. edodes, enhanced biosynthesis of this non-protein amino acid eliminates excess selenium.

Investigating different mechanisms for biogenic selenite transformations: Geobacter sulfurreducens, Shewanella oneidensis and Veillonella atypica

USGS Publications Warehouse

Pearce, C.I.; Pattrick, R.A.D.; Law, N.; Charnock, J.M.; Coker, V.S.; Fellowes, J.W.; Oremland, R.S.; Lloyd, J.R.

2009-01-01

The metal-reducing bacteria Geobacter sulfurreducens, Shewanella oneidensis and Veillonella atypica, use different mechanisms to transform toxic, bioavailable sodium selenite to less toxic, non-mobile elemental selenium and then to selenide in anaerobic environments, offering the potential for in situ and ex situ bioremediation of contaminated soils, sediments, industrial effluents, and agricultural drainage waters. The products of these reductive transformations depend on both the organism involved and the reduction conditions employed, in terms of electron donor and exogenous extracellular redox mediator. The intermediary phase involves the precipitation of elemental selenium nanospheres and the potential role of proteins in the formation of these structures is discussed. The bionanomineral phases produced during these transformations, including both elemental selenium nanospheres and metal selenide nanoparticles, have catalytic, semiconducting and light-emitting properties, which may have unique applications in the realm of nanophotonics. This research offers the potential to combine remediation of contaminants with the development of environmentally friendly manufacturing pathways for novel bionanominerals. ?? 2009 Taylor & Francis.

Biogenic selenium nanoparticles induce ROS-mediated necroptosis in PC-3 cancer cells through TNF activation.

PubMed

Sonkusre, Praveen; Cameotra, Swaranjit Singh

2017-06-07

Selenium is well documented to inhibit cancer at higher doses; however, the mechanism behind this inhibition varies widely depending on the cell type and selenium species. Previously, we have demonstrated that Bacillus licheniformis JS2 derived biogenic selenium nanoparticles (SeNPs) induce non-apoptotic cell death in prostate adenocarcinoma cell line, PC-3, at a minimal concentration of 2 µg Se/ml, without causing toxicity to the primary cells. However, the mechanism behind its anticancer activity was elusive. Our results have shown that these SeNPs at a concentration of 2 µg Se/ml were able to induce reactive oxygen species (ROS) mediated necroptosis in PC-3 cells by gaining cellular internalization. Real-time qPCR analysis showed increased expression of necroptosis associated tumor necrotic factor (TNF) and interferon regulatory factor 1 (IRF1). An increased expression of RIP1 protein was also observed at the translational level upon SeNP treatment. Moreover, the cell viability was significantly increased in the presence of necroptosis inhibitor, Necrostatin-1. Data suggest that our biogenic SeNPs induce cell death in PC-3 cells by the ROS-mediated activation of necroptosis, independent to RIP3 and MLKL, regulated by a RIP1 kinase.

Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity.

PubMed

Sharma, Arun K; Sk, Ugir Hossain; He, Pengfei; Peters, Jeffrey M; Amin, Shantu

2010-07-15

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. Herein, we describe an efficient synthesis of a novel isosteric selenium analog of the highly specific PPARbeta/delta ligand 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (GW501516; 1). The study examined the efficiency of the novel selenium analog 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-selenazol-5-yl)-methylsulfanyl)phenoxy-acetic acid (2) to activate PPARbeta/delta and the effect of ligand activation of PPARbeta/delta on cell proliferation and target gene expression in human HaCaT keratinocytes. The results showed that similar to GW501516, the Se-analog 2 increased expression of the known PPARbeta/delta target gene angiopoietin-like protein 4 (ANGPTL4); the compound 2 was comparable in efficacy as compared to GW501516. Consistent with a large body of evidence, the Se-analog inhibited cell proliferation in HaCaT keratinocytes similar to that observed with GW501516. In summary, the novel Se-analog 2 has been developed as a potent PPARbeta/delta ligand that may possess additional anti-cancer properties of selenium. 2010 Elsevier Ltd. All rights reserved.

Biofortification and phytoremediation of selenium in China

PubMed Central

Wu, Zhilin; Bañuelos, Gary S.; Lin, Zhi-Qing; Liu, Ying; Yuan, Linxi; Yin, Xuebin; Li, Miao

2015-01-01

Selenium (Se) is an essential trace element for humans and animals but at high concentrations, Se becomes toxic to organisms due to Se replacing sulfur in proteins. Selenium biofortification is an agricultural process that increases the accumulation of Se in crops, through plant breeding, genetic engineering, or use of Se fertilizers. Selenium phytoremediation is a green biotechnology to clean up Se-contaminated environments, primarily through phytoextraction and phytovolatilization. By integrating Se phytoremediation and biofortification technologies, Se-enriched plant materials harvested from Se phytoremediation can be used as Se-enriched green manures or other supplementary sources of Se for producing Se-biofortified agricultural products. Earlier studies primarily aimed at enhancing efficacy of phytoremediation and biofortification of Se based on natural variation in progenitor or identification of unique plant species. In this review, we discuss promising approaches to improve biofortification and phytoremediation of Se using knowledge acquired from model crops. We also explored the feasibility of applying biotechnologies such as inoculation of microbial strains for improving the efficiency of biofortification and phytoremediation of Se. The key research and practical challenges that remain in improving biofortification and phytoremediation of Se have been highlighted, and the future development and uses of Se-biofortified agricultural products in China has also been discussed. PMID:25852703

Organic Selenium Alleviated the Formation of Ethylene Glycol-Induced Calcium Oxalate Renal Calculi by Improving Osteopontin Expression and Antioxidant Capability in Dogs.

PubMed

Liu, Yongwang; Xu, Haibin; Zhong, Wenting; Shen, Qingpeng; Zhuang, Tenghan; Huang, Kehe

2015-12-01

Twenty one-year-old local male dogs were randomly assigned into four groups (five dogs per group). The control and the ethylene glycol (EG) groups were fed basal diets without and with EG, and the EG+sodium selenite (EG+SS) and EG+selenium yeast (EG+SY) groups were fed basal diets with EG containing SS and SY, respectively. Blood, urine, and renal samples were taken after 18 weeks of feeding. The results showed that compared with the control group, the serum calcium levels and antioxidase activities significantly decreased in the EG group. Serum creatinine, urea nitrogen, and malondialdehyde (MDA) levels and urine calcium and oxalate levels significantly increased. Calcium oxalate crystal deposition and osteopontin (OPN) messenger RNA and protein expression in the renal tissues significantly increased. These changes above in the EG group were reversed within limits by adding selenium in the diets (both EG+SS and EG+SY groups). Further, compared with the EG+SS group, the EG+SY group showed better effects in decreasing the formation of EG-induced calcium oxalate renal calculi and OPN expression and improving antioxidant capability in dogs. It indicates that organic selenium has the potential value to alleviate the formation of EG-induced calcium oxalate renal calculi.

[Spectrometric characteristics and underlying mechanisms of protective effects of selenium on Spirulina platensis against oxidative stress].

PubMed

Wu, Hua-lian; Chen, Tian-feng; Yin, Xi; Zheng, Wen-jie

2012-03-01

To investigate the possibility and the underlying mechanisms of sodium selenite as antagonist for oxidative stress, the authors examined the effects of pretreatment with selenium on the growth, morphology, spectrometric characteristics and content of reactive oxygen species (ROS) in Spirulina platensis (S. platensis) exposed to H2O2 stress for 24 h in the present study. The results showed that H2O2 induced obvious inhibition of growth and serious morphological damage. The intensity of absorbance peak at 440 nm increased, whereas the peaks at 620 and 680 nm decreased after exposed to H2O2. The emission and excitation spectrum of S. platensis decreased dramatically after H2O2 treatment, and the emission peak from phycocyanin exhibited blue-shift from 660 to 650 nm. The results of FTIR analysis showed that the positions of transmission peaks had no shift, but the relative intensity of characteristic bands from protein and polypeptides including amide I and amide II decreased. Furthermore, the intracellular ROS generation in S. platensis increased significantly in response to H2O2 treatment. In contrast, pretreatments of the cells with selenium for 24 h significantly prevented the H2O2-induced oxidative damages in a dose-dependent manner. Taken together, our results indicate that pretreatments with selenium could prevent ROS overproduction in S. platensis and improve its antioxidant ability. Moreover, selenium could also reduce the effects of free radicals on energy harvest and energy transfer in S. platensis that play vital roles in its photosynthesis.

Effect of supplementation with organic selenium on mercury status as measured by mercury in pubic hair.

PubMed

Seppänen, K; Kantola, M; Laatikainen, R; Nyyssönen, K; Valkonen, V P; Kaarlöpp, V; Salonen, J T

2000-06-01

The purpose of this study was to evaluate the effect of four months of yeast-based selenium supplementation on selenium and mercury status in subjects with low serum selenium. The study was carried out in Rakvere, Estonia. Pubic hair mercury, serum selenium and blood selenium concentrations in 23 subjects (serum selenium < 90 micrograms/l) were investigated before and after selenium supplementation. Thirteen subjects were randomized into the selenium supplementation group and ten into the placebo group. The selenium supplementation group received daily 100 micrograms of selenomethionine. Selenium supplementation reduced pubic hair mercury level by 34% (p = 0.005) and elevated serum selenium by 73% and blood selenium by 59% in the supplemented group (p < 0.001 for both). The study indicates that mercury accumulation in pubic hair can be reduced by dietary supplementation with small daily amounts of organic selenium in a short range of time.

Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation.

PubMed

Steen, Arvid; Strøm, Turid; Bernhoft, Aksel

2008-03-31

Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs. Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements. In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 microg/g) than ewe pens that received inorganic selenium (mean 0.24 microg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 microg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 microg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight). Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation.

Organic selenium supplementation increased selenium concentrations in ewe and newborn lamb blood and in slaughter lamb meat compared to inorganic selenium supplementation

PubMed Central

Steen, Arvid; Strøm, Turid; Bernhoft, Aksel

2008-01-01

Background Selenium is part of the antioxidant defence system in animals and humans. The available selenium concentration in soil is low in many regions of the world. The purpose of this study was to evaluate the effect of organic versus inorganic selenium supplementation on selenium status of ewes, their lambs, and slaughter lambs. Methods Ewes on four organic farms were allocated five or six to 18 pens. The ewes were given either 20 mg/kg inorganic selenium as sodium selenite or organic selenium as selenized nonviable yeast supplementation for the two last months of pregnancy. Stipulated selenium concentrations in the rations were below 0.40 mg/kg dry matter. In addition 20 male lambs were given supplements from November until they were slaughtered in March. Silage, hay, concentrates, and individual ewe blood samples were taken before and after the mineral supplementation period, and blood samples were taken from the newborn lambs. Blood samples from ewes and lambs in the same pens were pooled. Muscle samples were taken from slaughter lambs in March. Selenium concentrations were determined by atomic absorption spectrometry with a hydride generator system. In the ANOVA model, selenium concentration was the continuous response variable, and selenium source and farm were the nominal effect variables. Two-sample t-test was used to compare selenium concentrations in muscle samples from the slaughtered lambs that received either organic or inorganic selenium supplements. Results In all ewe pens the whole blood selenium concentrations increased during the experimental period. In addition, ewe pens that received organic selenium had significantly higher whole blood selenium concentrations (mean 0.28 μg/g) than ewe pens that received inorganic selenium (mean 0.24 μg/g). Most prominent, however, was the difference in their lambs; whole blood mean selenium concentration in lambs from mothers that received organic selenium (mean 0.27 μg/g) was 30% higher than in lambs from mothers that received inorganic selenium (mean 0.21 μg/g). Slaughter lambs that received organic selenium had 50% higher meat selenium concentrations (mean 0.12 mg/kg wet weight) than lambs that received inorganic selenium (mean 0.08 mg/kg wet weight). Conclusion Organic selenium supplementation gave higher selenium concentration in ewe and newborn lamb blood and slaughter lamb meat than inorganic selenium supplementation. PMID:18377659

Isolation, purification and characterisation of selenium-containing polysaccharides and proteins in selenium-enriched Radix puerariae.

PubMed

Zou, Ye; Zhao, Ting; Mao, Guanghua; Zhang, Min; Zheng, Daheng; Feng, Weiwei; Wang, Wei; Wu, Xiangyang; Yang, Liuqing

2014-01-30

Selenium (Se) is an essential dietary mineral and Radix puerariae (RP) (the dried root of Pueraria lobata Willd.) is a botanical supplement widely used as a nutraceutical. Food enriched with Se provides a feasible and economic approach for production of organic Se compounds. However, little is known about Se-enriched RP and the structure of Se-containing polysaccharides and proteins derived from Se-enriched RP. The organic form of Se accounted for 82.42% of total content. Purification by DEAE-52 and Sephadex G-100 column chromatography yielded three single fractions--RP-SeP-11, RP-SeP-22 and RP-SeP-33--with Se contents of 0.9562 × 10⁻³, 0.6113 × 10⁻³ and 0.3827 × 10⁻³ g kg⁻¹, respectively. RP-SeP-11 (3.5 kDa) was made of glucose, RP-SeP-22 (19.6 kDa) was composed of xylose and glucose, and RP-SeP-33 (97.9 kDa) was made up galactose, mannose and glucose. Two Se-containing proteins were obtained with Se content of 3.175 × 10⁻³ and 4.328 × 10⁻³ g kg⁻¹, respectively. One appeared as three subunits with molecular masses of 43.0, 29.0 and 17.8 kDa while the other appeared as two subunits with molecular masses of 43.0 and 26.3 kDa. The results provide a basis for promoting the utilisation of RP resources enriched with Se as a promising tool for the food industry and are significant for its contribution to Se biochemistry in plants. © 2013 Society of Chemical Industry.

Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

PubMed Central

Yim, Sun Hee; Gladyshev, Vadim N.; Lee, Seung-Rock

2014-01-01

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein. PMID:24751718

Characterization of mammalian selenoprotein o: a redox-active mitochondrial protein.

PubMed

Han, Seong-Jeong; Lee, Byung Cheon; Yim, Sun Hee; Gladyshev, Vadim N; Lee, Seung-Rock

2014-01-01

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein.

Acute toxicity of functionalized single wall carbon nanotubes: A biochemical, histopathologic and proteomics approach.

PubMed

Ahmadi, Homa; Ramezani, Mohammad; Yazdian-Robati, Rezvan; Behnam, Behzad; Razavi Azarkhiavi, Kamal; Hashem Nia, Azadeh; Mokhtarzadeh, Ahad; Matbou Riahi, Maryam; Razavi, Bibi Marjan; Abnous, Khalil

2017-09-25

Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice). One or 7 days after intravenous injection, the mice were killed and serum and livers were collected. The oxidative stress markers, biochemical and histopathological changes were studied. Subsequently, proteomics approach was used to investigate the alterations of protein expression profiles in the liver. Results showed that there were not any significant differences in malondealdehyde (MDA), glutathione (GSH) levels and biochemical enzymes (ALT and AST) between groups, while the histopathological observations of livers showed some injuries. The results of proteomics analysis revealed indolethylamine N-Methyltransferase (INMT), glycine N-Methyltransferase (GNMT), selenium binding protein (Selenbp), thioredoxin peroxidase (TPx), TNF receptor associated protein 1(Trap1), peroxiredoxin-6 (Prdx6), electron transport flavoprotein (Etf-α), regucalcin (Rgn) and ATP5b proteins were differentially expressed in functionalized SWCNTs groups. Western blot analyses confirmed that the changes in Prdx6 were consistent with 2-DE gel analysis. In summary, acute toxicological study on two functionalized SWCNTs did not show any significant toxicity at selected doses. Proteomics analysis also showed that following exposure to functionalized SWCNTs, the expression of some proteins with antioxidant activity and detoxifying properties were increased in liver tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Selenium Deficiency Influences the Expression of Selenoproteins and Inflammatory Cytokines in Chicken Aorta Vessels.

PubMed

Du, Qiang; Yao, Haidong; Yao, Linlin; Zhang, Ziwei; Lei, Xingen; Xu, Shiwen

2016-10-01

Selenium deficiency is known to cause cardiovascular diseases. However, the role of Se deficiency in causing oxidative damage and inflammation injury to the aorta vessels of chickens is not well known. In the present study, 180 1-day-old chickens were randomly divided into two groups, a low-Se group (L group) and a control-Se group (C group). The messenger RNA (mRNA) levels of 25 selenoproteins, the mRNA and protein expression levels of inflammatory cytokines (including NF-κB, TNF-α, COX-2, and PTGES), and the antioxidant levels in chicken aorta vessels were examined. The results showed that the mRNA levels of 25 selenoproteins and the activity of Gpx were decreased, while the mRNA and protein expression levels of inflammatory cytokines and the MDA content were increased by Se deficiency in chicken aorta vessels. The data from the present study indicated that Se deficiency decreases the expression of selenoproteins, reduces antioxidant function, and increases the expression of inflammatory factors in chicken aorta vessels.

[Effects of nano-selenium on the capability of learning memory and the activity of Se-protein of mice].

PubMed

Qin, Fenju; Ye, Yaxin; Yao, Xuemei

2008-07-01

To investigate the effects of Nano-Selenium on learning memory capability and activity of two kinds of Se-protein in brain and liver of mice, Na, SeO3 as the controls. The mice were administred two kinds of origin (doses of 1 microgSe/d, 2 microgSe/d, 4 microgSe/d) Se by intra-gastric injection respectively. The learning memory ability of the mice was measured by Y-type maze test. Activities of glutathione peroxidase (GSH-Px) and iodothyronine deiodinase (ID) in brain and liver were also measured. In comparison with the control groups of Na2 Se03, learning memory abilities were improved and activities of ID and GSH-Px (P < 0.01 or P < 0.05) of brain and liver were increased in Nano-Se treatment groups. Nano-Se could improve learning memory ability of mice, and enhance ID and GSH-Px activities of brain and liver in mice.

Distribution and mode of occurrence of selenium in US coals

USGS Publications Warehouse

Coleman, L.; Bragg, L.J.; Finkelman, R.B.

1993-01-01

Selenium excess and deficiency have been established as the cause of various health problems in man and animals. Combustion of fossil fuels, especially coal, may be a major source of the anthropogenic introduction of selenium in the environment. Coal is enriched in selenium relative to selenium's concentration in most other rocks and relative to selenium in the Earth's crust. Data from almost 9,000 coal samples have been used to determine the concentration and distribution of selenium in US coals. The geometric mean concentration of selenium in US coal is 1.7 ppm. The highest mean selenium value (geometric mean 4.7 ppm) is in the Texas Region. Atlantic Coast (Virginia and North Carolina) and Alaska coals have the lowest geometric means (0.2 and 0.42 ppm, respectively). All western coal regions have mean selenium concentrations of less than 2.0 ppm. In contrast, all coal basins east of the Rocky Mountains (except for several small basins in Rhode Island, Virginia, and North Carolina) have mean selenium values of 1.9 or greater. Generally, variations in selenium concentration do not correlate with variations in ash yield, pyritic sulphur, or organic sulphur concentrations. This may be the result of multiple sources of selenium; however, in some non-marine basins with restricted sources of selenium, selenium has positive correlations with other coal quality parameters. Selenium occurs in several forms in coal but appears to be chiefly associated with the organic fraction, probably substituting for organic sulphur. Other important forms of selenium in coal are selenium-bearing pyrite, selenium-bearing galena, and lead selenide (clausthalite). Water-soluble and ion-exchangeable selenium also have been reported. ?? 1993 Copyright Science and Technology Letters.

Maternal-fetal transfer of selenium in the mouse.

PubMed

Burk, Raymond F; Olson, Gary E; Hill, Kristina E; Winfrey, Virginia P; Motley, Amy K; Kurokawa, Suguru

2013-08-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.

Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

PubMed

Shafik, Noha M; El Batsh, Maha M

2016-01-01

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p < 0.05) which were confirmed by histopathological examination. Additionally, arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p < 0.05) and decreased activity of thioredoxin reductase, values of total anti-oxidant capacity, and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression. Significant improvement in all assessed parameters was observed in rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

Estimation of Mineral and Trace Element Profile in Bubaline Milk Affected with Subclinical Mastitis.

PubMed

Singh, Mahavir; Yadav, Poonam; Sharma, Anshu; Garg, V K; Mittal, Dinesh

2017-04-01

The milk samples from buffaloes of Murrah breed at mid lactation stage, reared at an organised dairy farm, were screened for subclinical mastitis based on bacteriological examination and somatic cell count following International Dairy Federation criteria. Milk samples from subclinical mastitis infected and healthy buffaloes were analysed to evaluate physicochemical alterations in terms of protein, fat, pH, electrical conductivity, chloride, minerals (sodium, potassium and calcium) and trace elements (iron, zinc, copper and selenium). In the present study, protein, fat, zinc, iron, calcium and selenium content was significantly lower (P < 0.001), while pH and electrical conductivity were significantly higher in mastitic milk as compared to normal milk. Concentration of electrolytes mainly sodium and chloride significantly increased with higher somatic cell count in mastitic milk and to maintain osmolality; potassium levels decreased proportionately. Correlation matrix revealed significantly positive interdependences of somatic cell count with pH, electrical conductivity, sodium and chloride. However, protein, fat, calcium and potassium were correlated negatively with elevated somatic cell count in mastitic milk. It is concluded that udder infections resulting in elevated somatic cells may alter the mineral and trace element profile of milk, and magnitude of changes may have diagnostic and prognostic value.

Monodispersed spherical shaped selenium nanoparticles (SeNPs) synthesized by Bacillus subtilis and its toxicity evaluation in zebrafish embryos

NASA Astrophysics Data System (ADS)

Chandramohan, Subburaman; Sundar, Krishnan; Muthukumaran, Azhaguchamy

2018-02-01

Selenium is one of the essential elements involved in antioxidative and antiinflammatory effects in human body. By naturally, selenium ions are metabolised and converted into nano selenium. Now a days there is an increasing attention on applications of nanoparticles in therapeutic field. In the present study Bacillus subtilis was used to convert sodium selenite to SeNPs. The synthesized SeNPs were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) coupled with Energy Dispersive X ray spectroscopy (EDX). The presence of SeNPs was confirmed by the formation of red colour. The bands were sharp with broad absorption peaks at 3562 cm-1 and 1678-1 cm in FTIR which showed that the bacterial proteins were responsible for the reduction of sodium selenite to SeNPs. The average size of the SeNPs was 334 nm and were spherical in shape with uniform distribution. The XRD data confirmed that SeNPs were of amorphous in nature. The zeta potential of SeNPs was negative in charge which indicated high stability. In the present study zebrafish embryos were used to study the toxicity of SeNPs and the results showed that the concentration beyond 10 μg ml-1 leads to toxic effects in embryos/hatchlings. The lesser concentration of SeNPs can be useful in various biomedical applications.

Relationships for mercury and selenium in muscle and ova of gravid freshwater fish.

PubMed

Donald, David B

2016-10-01

At high concentrations, mercury (Hg) is toxic to vertebrates, causing neurological, behavioral, and teratological dysfunction. Selenium (Se) not only is an essential element but also has a high affinity for Hg, binding to organic methyl mercury at a molar ratio of Se/Hg of 1:1. Ratios of <1 increase risk of Hg toxicity. For gravid fish, low concentrations of Se in ova could increase potential for Hg toxicity, compromising embryonic development and fitness of fry. Mercury and selenium concentrations and ratios were investigated in the muscle and ovaries of six species from five families of fish to assess potential for risk to ecological fitness. Molar ratios of Se/Hg in muscle were typically >18 for lower trophic level species but ≤2 for piscivores. For all species combined, the concentrations of Hg in ova were significantly related to concentrations of Hg in muscle. Concentrations of Se in ova versus muscle showed a similar significant relationship that was independent of muscle Hg concentration. Mean ova molar Se/Hg ratios were high, ranging from 69 to 955 for the 6 species. However, a declining relationship between the ova Se/Hg molar ratio and the muscle concentration of Hg for all species combined suggests that development of ova and fry might be compromised for those piscivores with the highest muscle Hg concentrations because of Hg-related Se deficiency.

Speciation of organic and inorganic selenium in selenium-enriched rice by graphite furnace atomic absorption spectrometry after cloud point extraction.

PubMed

Sun, Mei; Liu, Guijian; Wu, Qianghua

2013-11-01

A new method was developed for the determination of organic and inorganic selenium in selenium-enriched rice by graphite furnace atomic absorption spectrometry detection after cloud point extraction. Effective separation of organic and inorganic selenium in selenium-enriched rice was achieved by sequentially extracting with water and cyclohexane. Under the optimised conditions, the limit of detection (LOD) was 0.08 μg L(-1), the relative standard deviation (RSD) was 2.1% (c=10.0 μg L(-1), n=11), and the enrichment factor for selenium was 82. Recoveries of inorganic selenium in the selenium-enriched rice samples were between 90.3% and 106.0%. The proposed method was successfully applied for the determination of organic and inorganic selenium as well as total selenium in selenium-enriched rice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Maternal-fetal transfer of selenium in the mouse

PubMed Central

Burk, Raymond F.; Olson, Gary E.; Hill, Kristina E.; Winfrey, Virginia P.; Motley, Amy K.; Kurokawa, Suguru

2013-01-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.—Burk, R. F., Olson, G. E., Hill, K. E., Winfrey, V. P., Motley, A. K., and Kurokawa, S. Maternal-fetal transfer of selenium in the mouse. PMID:23651543

Selenium: environmental significance, pollution, and biological treatment technologies.

PubMed

Tan, Lea Chua; Nancharaiah, Yarlagadda V; van Hullebusch, Eric D; Lens, Piet N L

2016-01-01

Selenium is an essential trace element needed for all living organisms. Despite its essentiality, selenium is a potential toxic element to natural ecosystems due to its bioaccumulation potential. Though selenium is found naturally in the earth's crust, especially in carbonate rocks and volcanic and sedimentary soils, about 40% of the selenium emissions to atmospheric and aquatic environments are caused by various industrial activities such as mining-related operations. In recent years, advances in water quality and pollution monitoring have shown that selenium is a contaminant of potential environmental concern. This has practical implications on industry to achieve the stringent selenium regulatory discharge limit of 5μgSeL(-1) for selenium containing wastewaters set by the United States Environmental Protection Agency. Over the last few decades, various technologies have been developed for the treatment of selenium-containing wastewaters. Biological selenium reduction has emerged as the leading technology for removing selenium from wastewaters since it offers a cheaper alternative compared to physico-chemical treatments and is suitable for treating dilute and variable selenium-laden wastewaters. Moreover, biological treatment has the advantage of forming elemental selenium nanospheres which exhibit unique optical and spectral properties for various industrial applications, i.e. medical, electrical, and manufacturing processes. However, despite the advances in biotechnology employing selenium reduction, there are still several challenges, particularly in achieving stringent discharge limits, the long-term stability of biogenic selenium and predicting the fate of bioreduced selenium in the environment. This review highlights the significance of selenium in the environment, health, and industry and biotechnological advances made in the treatment of selenium contaminated wastewaters. The challenges and future perspectives are overviewed considering recent biotechnological advances in the management of these selenium-laden wastewaters. Copyright © 2016 Elsevier Inc. All rights reserved.

Bio-transformation of selenium in Se-enriched bacterial strains of Lactobacillus casei.

PubMed

Kurek, Eliza; Ruszczyńska, Anna; Wojciechowski, Marcin; Łuciuk, Anna; Michalska-Kacymirow, Magdalena; Motyl, Ilona; Bulska, Ewa

Selenium is an element of very great importance for the proper functioning of the human body, mainly due to its antioxidant properties. Selenium exhibits a preventive effect in the case of cardiovascular disease, the immune system, male infertility and inhibits the toxic action of other agents. Selenium is important for Hashimoto's disease. Intake of selenium in the diet slows the aging process. The biological and toxicological effects of selenium strongly depend on its chemical form. Some organisms for example: plant, yeast, are capable of metabolizing low bioavailable selenium compounds (inorganic selenium) into its high bioavailable forms (organic selenium). The aim of this study was to investigate the bio-transformation of selenium by Lactobacillus bacteria towards the characterisation of selenium metabolites. The speciation of selenium was evaluated by high performance liquid chromatography with inductively coupled plasma mass spectrometry detector. The extraction of selenium species from lyophilized bacteria was executed with water, the mixture of lipase and protease, as well as lisozyme and sodium dodecyl sulphate. All investigated bacteria strains cultivated in the presence of Na2SeO3 effectively uptake selenium. Surprisingly, none of the applied extraction media exhibited a strong power to release the majority of the uptaken selenium compounds. Thus a maximum of 10% of the selenium was extracted from bacteria exposed to the enzymes. However, it was found that Lactobacillus bacteria are able to metabolize inorganic ions of selenium (IV) into Se-methionine, Se-methyloselenocysteine and other unidentified forms. The study confirmed the ability of probiotic bacteria to biotransform inorganic selenium into its organic derivatives. Therefore, Se-enriched bacteria can be considered as an addition to the functional food. selenium speciation, extraction procedure, Lactobacillus casei bacteria, Lactic acid bacteria (LAB), HPLC ICP-MS, functional food.

Parenteral selenium and vitamin E supplementation to lambs: hematology, serum biochemistry, performance, and relationship with other trace elements.

PubMed

Mohri, Mehrdad; Ehsani, Abdollah; Norouzian, M A; Bami, Mohammad Heidarpour; Seifi, Hesam A

2011-03-01

Most regions in Iran are generally selenium (Se) deficient and all mineral premixes which used in farm animals contain Se in the form of sodium selenite. The objective of this study was to evaluate the effects of injected Se and vitamin E (vit E) on hematology, serum proteins, and performance of lambs during the period which the animals are at risk of Se and/or vit E deficiency. The study also aims to determine the relationship between selenium injection and the levels of other trace elements in blood serum of lambs. A total of 16 lambs of Baloochi breed (age, 70 ± 7 days and weight, 15.2 ± 1.4) were enrolled in the study. The animals were divided into two groups. In the test group, vit E and Se injected at a dose of 0.2 ml/kg BW (Vetoquinol, Selepherol®, Lure Cedex, France, α-tocopherol acetate 3.82 g/100 ml plus sodium selenite 0.023 g/100 ml) at the enrollment. Control lambs were received equal amounts of normal saline as placebo. Blood was sampled from the jugular vein at the beginning of the study (enrollment, before injection of vit E and selenium and saline) and at days 7, 14, 21, and 28 of experiment. The amounts of total serum protein, albumin, glucose, iron, copper, zinc, creatine kinase (CK), and aspartate aminotransferase (AST) and Se were measured. The concentration of globulin was calculated as the difference between total serum protein and albumin. For evaluation of growth and health, body weight of all the lambs was measured at day 0 of the experiment and the sampling times and days of treatment for each lamb were recorded. Treatment with Se and vit E decreased the activities of CK and AST compared to the controls (p < 0.05). Age (sampling time) had significant effects on the values of Se, iron, zinc, AST, hemoglobin, total protein, glucose, weight, height, and length (p < 0.05). Significant interactions between sampling time and group were seen for CK, AST, iron, glucose, weight, and length. No significant differences were seen for total weight gain (control, 3.48 ± 0.75 kg; test, 3.85 ± 0.9 kg), and average daily gain (control, 0.12 ± 0.03 kg; test, 0.14 ± 0.03 kg) between trial groups.

Chemical Kinetic and Molecular Genetic Study of Selenium Oxyanion Reduction by Enterobactor cloacae SLD1a-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma,J.; Kobayashi, D.; Yee, N.

2007-01-01

Microbial processes play an important role in the redox transformations of toxic selenium oxyanions. In this study, we employed chemical kinetic and molecular genetic techniques to investigate the mechanisms of Se(IV) and Se(VI) reduction by the facultative anaerobe Enterobacter cloacae SLD1a-1. The rates of microbial selenium oxyanion reduction were measured as a function of initial selenium oxyanion concentration (0-1.0 mM) and temperature (10-40 C), and mutagenesis studies were performed to identify the genes involved in the selenium oxyanion reduction pathway. The results indicate that Se(IV) reduction is significantly more rapid than the reduction of Se(VI). The kinetics of the reductionmore » reactions were successfully quantified using the Michaelis-Menten kinetic equation. Both the rates of Se(VI) and Se(IV) reduction displayed strong temperature-dependence with Ea values of 121 and 71.2 kJ/mol, respectively. X-ray absorption near-edge spectra collected for the precipitates formed by Se(VI) and Se(IV) reduction confirmed the formation of Se(0). A miniTn5 transposon mutant of E. cloacae SLD1a-1 was isolated that had lost the ability to reduce Se(VI) but was not affected in Se(IV) reduction activity. Nucleotide sequence analysis revealed the transposon was inserted within a tatC gene, which encodes for a central protein in the twin arginine translocation system. Complementation by the wild-type tatC sequence restored the ability of mutant strains to reduce Se(VI). The results suggest that Se(VI) reduction activity is dependent on enzyme export across the cytoplasmic membrane and that reduction of Se(VI) and Se(IV) are catalyzed by different enzymatic systems.« less

Selenoproteins-What unique properties can arise with selenocysteine in place of cysteine?

PubMed

Arnér, Elias S J

2010-05-01

The defining entity of a selenoprotein is the inclusion of at least one selenocysteine (Sec) residue in its sequence. Sec, the 21st naturally occurring genetically encoded amino acid, differs from its significantly more common structural analog cysteine (Cys) by the identity of a single atom: Sec contains selenium instead of the sulfur found in Cys. Selenium clearly has unique chemical properties that differ from sulfur, but more striking are perhaps the similarities between the two elements. Selenium was discovered by Jöns Jacob Berzelius, a renowned Swedish scientist instrumental in establishing the institution that would become Karolinska Institutet. Written at the occasion of the bicentennial anniversary of Karolinska Institutet, this mini review focuses on the unique selenium-derived properties that may potentially arise in a protein upon the inclusion of Sec in place of Cys. With 25 human genes encoding selenoproteins and in total several thousand selenoproteins yet described in nature, it seems likely that the presence of that single selenium atom of Sec should convey some specific feature, thereby explaining the existence of selenoproteins in spite of demanding and energetically costly Sec-specific synthesis machineries. Nonetheless, most, if not all, of the currently known selenoproteins are also found as Cys-containing non-selenoprotein orthologues in other organisms, wherefore any potentially unique properties of selenoproteins are yet a matter of debate. The pK(a) of free Sec (approximately 5.2) being significantly lower than that of free Cys (approximately 8.5) has often been proposed as one of the unique features of Sec. However, as discussed herein, this pK(a) difference between Sec and Cys can hardly provide an evolutionary pressure for maintenance of selenoproteins. Moreover, the typically 10- to 100-fold lower enzymatic efficiencies of Sec-to-Cys mutants of selenoprotein oxidoreductases, are also weak arguments for the overall existence of selenoproteins. Here, it is however emphasized that the inherent high nucleophilicity of Sec and thereby its higher chemical reaction rate with electrophiles, as compared to Cys, seems to be a truly unique property of Sec that cannot easily be mimicked by the basicity of Cys, even within the microenvironment of a protein. The chemical rate enhancement obtained with Sec can have other consequences than those arising from a low redox potential of some Cys-dependent proteins, typically aiming at maintaining redox equilibria. Another unique aspect of Sec compared to Cys seems to be its efficient potency to support one-electron transfer reactions, which, however, has not yet been unequivocally shown as a Sec-dependent step during the natural catalysis of any known selenoprotein enzyme. Copyright 2010 Elsevier Inc. All rights reserved.

Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis.

PubMed

Ingold, Irina; Berndt, Carsten; Schmitt, Sabine; Doll, Sebastian; Poschmann, Gereon; Buday, Katalin; Roveri, Antonella; Peng, Xiaoxiao; Porto Freitas, Florencio; Seibt, Tobias; Mehr, Lisa; Aichler, Michaela; Walch, Axel; Lamp, Daniel; Jastroch, Martin; Miyamoto, Sayuri; Wurst, Wolfgang; Ursini, Fulvio; Arnér, Elias S J; Fradejas-Villar, Noelia; Schweizer, Ulrich; Zischka, Hans; Friedmann Angeli, José Pedro; Conrad, Marcus

2018-01-25

Selenoproteins are rare proteins among all kingdoms of life containing the 21 st amino acid, selenocysteine. Selenocysteine resembles cysteine, differing only by the substitution of selenium for sulfur. Yet the actual advantage of selenolate- versus thiolate-based catalysis has remained enigmatic, as most of the known selenoproteins also exist as cysteine-containing homologs. Here, we demonstrate that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis. Yet the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX4, thereby preventing fatal epileptic seizures. Mechanistically, selenocysteine utilization by GPX4 confers exquisite resistance to irreversible overoxidation as cells expressing a cysteine variant are highly sensitive toward peroxide-induced ferroptosis. Remarkably, concomitant deletion of all selenoproteins in Gpx4 cys/cys cells revealed that selenoproteins are dispensable for cell viability provided partial GPX4 activity is retained. Conclusively, 200 years after its discovery, a specific and indispensable role for selenium is provided. Copyright © 2017 Elsevier Inc. All rights reserved.

Mercury and selenium binding biomolecules in terrestrial mammals (Cervus elaphus and Sus scrofa) from a mercury exposed area.

PubMed

Ropero, M J Patiño; Fariñas, N Rodríguez; Krupp, E; Mateo, R; Nevado, J J Berzas; Martín-Doimeadios, R C Rodríguez

2016-06-01

Mercury (Hg) is likely bound to large biomolecules (e.g. proteins) in living organisms, and in order to assess Hg metabolic pathways and possible toxicological effects, it is essential to study these Hg containing biomolecules. However, the exact nature of most metal binding biomolecules is unknown. Such studies are still in their infancy and information on this topic is scarce because the analysis is challenging, mainly due to their lability upon digestion or extraction from the tissue. New analytical methods that allow complex Hg-biomolecules to be analysed intact are needed and only few very recent studies deal with this approach. Therefore, as an initial step towards the characterization of Hg containing biomolecules, an analytical procedure has been optimised using size-exclusion chromatography (SEC) with inductively coupled plasma mass spectrometry (ICP-MS) detection. We applied this technique to elucidate the distribution and elution profile of Hg and Se, and some physiological important elements such as Fe, Ni, Zn and Cu, to assess metal binding profiles in liver and kidney samples of red deer (Cervus elaphus) and wild boar (Sus scrofa) who roam freely within the largest Hg mining district on Earth, Almadén in Spain. Elemental fractionation profiles of the extracts from different tissues were obtained using two different SEC columns (BioSep-SEC-S2000 GL 300-1kDa and Superdex 75 10/300 GL 70-3kDa). Similar profiles of Hg were observed in red deer and wild boar; however, significant differences were evident for liver and kidney. Moreover, the profiles of Se showed a single peak at high-medium molecular weight in all investigated tissues, while co-elution of Hg with Fe, Ni, Zn and Cu was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

An X-ray structural study of pyruvate dehydrogenase kinase: A eukaryotic serine kinase with a prokaryotic histidine-kinase fold

NASA Astrophysics Data System (ADS)

Steussy, Calvin Nicklaus, Jr.

2001-07-01

Pyruvate Dehydrogenase Kinase is an enzyme that controls the flow of glucose through the eukaryotic cell and contributes to the pathology of diabetes mellitus. Early work on this kinase demonstrated that it has an amino acid sequence much like bacterial histidine kinases, but an activity similar to that of modern serine/threonine kinases. This project utilized the techniques of X-ray crystallography to determine molecular structure of pyruvate dehydrogenase kinase, isozyme 2. The structure was phased using selenium substituted for sulfur in methionine residues, and data at multiple wavelengths was collected at the National Synchrotron Light Source, Brookhaven National Laboratories. PDK 2 was found to fold into a two-domain monomer that forms a dimer through two beta sheets in the C-terminal domain. The N-terminal domain is an alpha-helical bundle while the C-terminal domain is an alpha/beta sandwich. The fold of the C-terminal domain is very similar to that of the prokaryotic histidine kinases, indicating that they share a common ancestor. The catalytic mechanism, however, has evolved to use general base catalysis to activate the serine substrate, rather than the direct nucleophilic attack by the imidazole sidechain used in the prokaryotic kinases. Thus, the structure of the protein echoes its prokaryotic ancestor, while the chemical mechanism has adapted to a serine substrate. The electrostatic surface of PDK2 leads to the suggestion that the lipoyl domain of the pyruvate dehydrogenase kinase, an important associated structure, may bind in the cleft formed between the N- and C-terminal domains. In addition, a network of hydrogen bonds directly connects the nucleotide binding pocket to the dimer interface, suggesting that there may be some interaction between dimer formation and ATP binding or ADP release.

Percutaneous absorption of selenium sulfide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farley, J.; Skelly, E.M.; Weber, C.B.

1986-01-01

The purpose of this study was to determine selenium levels in the urine of Tinea patients before and after overnight application of a 2.5% selenium sulfide lotion. Selenium was measured by atomic absorption spectroscopy (AAS). Hydride generation and carbon rod atomization were studied. It was concluded from this study that selenium is absorbed through intact skin. Selenium is then excreted, at least partially, in urine, for at least a week following treatment. The data show that absorption and excretion of selenium vary on an individual basis. Selenium levels in urine following a single application of selenium sulfide lotion do notmore » indicate that toxic amounts of selenium are being absorbed. Repeated treatments with SeS/sub 2/ result in selenium concentrations in urine which are significantly higher than normal. Significant matrix effects are observed in the carbon rod atomization of urine samples for selenium determinations, even in the presence of a matrix modifier such as nickel. The method of standard additions is required to obtain accurate results in the direct determination of selenium in urine by carbon rod AAS.« less

Selenium.

PubMed

Barceloux, D G

1999-01-01

The 4 natural oxidation states of selenium are elemental selenium (0), selenide (-2), selenite (+4), and selenate (+6). Inorganic selenate and selenite predominate in water whereas organic selenium compounds (selenomethionine, selenocysteine) are the major selenium species in cereal and in vegetables. The principal applications of selenium include the manufacture of ceramics, glass, photoelectric cells, pigments, rectifiers, semiconductors, and steel as well as use in photography, pharmaceutical production, and rubber vulcanizing. High concentrations of selenium in surface and in ground water usually occur in farm areas where irrigation water drains from soils with high selenium content (Kesterson Reservoir, California) or in lakes receiving condenser cooling water from coal-fired electric power plants (Belews Lake, North Carolina). For the general population, the primary pathway of exposure to selenium is food, followed by water and air. Both selenite and selenate possess substantial bioavailability. However, plants preferentially absorb selenates and convert them to organic compounds. Aquatic organisms (e.g., bivalves) can accumulate and magnify selenium in the food chain. Selenium is an essential component of glutathione peroxidase, which is an important enzyme for processes that protect lipids in polyunsaturated membranes from oxidative degradation. Inadequate concentrations of selenium in the Chinese diet account, at least in part, for the illness called Keshan disease. Selenium deficiency occurs in the geographic areas where Balkan nephropathy appears, but there is no direct evidence that selenium deficiency contributes to the development of this chronic, progressive kidney disease. Several lines of scientific inquiry suggest that an increased risk of cancer occurs as a result of low concentrations of selenium in the diet; however, insufficient evidence exists at the present time to recommend the use of selenium supplements for the prevention of cancer. The toxicity of most forms of selenium is low and the toxicity depends on the chemical form of selenium. The acute ingestion of selenious acid is almost invariably fatal, preceded by stupor, hypotension, and respiratory depression. Chronic selenium poisoning has been reported in China where changes in the hair and nails resulted from excessive environmental exposures to selenium. Garlic odor on the breath is an indication of excessive selenium exposure as a result of the expiration of dimethyl selenide. The US National Toxicology Program lists selenium sulfide as an animal carcinogen, but there is no evidence that other selenium compounds are carcinogens.

Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium

PubMed Central

Wang, Hang; Li, Tsung-Lin; Hsia, Simon; Su, I-Li; Chan, Yi-Lin; Wu, Chang-Jer

2015-01-01

Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy. PMID:25797259

Dietary selenium affects host selenoproteome expression by influencing the gut microbiota

PubMed Central

Kasaikina, Marina V.; Kravtsova, Marina A.; Lee, Byung Cheon; Seravalli, Javier; Peterson, Daniel A.; Walter, Jens; Legge, Ryan; Benson, Andrew K.; Hatfield, Dolph L.; Gladyshev, Vadim N.

2011-01-01

Colonization of the gastrointestinal tract and composition of the microbiota may be influenced by components of the diet, including trace elements. To understand how selenium regulates the intestinal microflora, we used high-throughput sequencing to examine the composition of gut microbiota of mice maintained on selenium-deficient, selenium-sufficient, and selenium-enriched diets. The microbiota diversity increased as a result of selenium in the diet. Specific phylotypes showed differential effects of selenium, even within a genus, implying that selenium had unique effects across microbial taxa. Conventionalized germ-free mice subjected to selenium diets gave similar results and showed an increased diversity of the bacterial population in animals fed with higher levels of selenium. Germ-free mice fed selenium diets modified their selenoproteome expression similar to control mice but showed higher levels and activity of glutathione peroxidase 1 and methionine-R-sulfoxide reductase 1 in the liver, suggesting partial sequestration of selenium by the gut microorganisms, limiting its availability for the host. These changes in the selenium status were independent of the levels of other trace elements. The data show that dietary selenium affects both composition of the intestinal microflora and colonization of the gastrointestinal tract, which, in turn, influence the host selenium status and selenoproteome expression.—Kasaikina, M. V., Kravtsova, M. A., Lee, B. C., Seravalli, J., Peterson, D. A., Walter, J., Legge, R., Benson, A. K., Hatfield, D. L., Gladyshev, V. N. Dietary selenium affects host selenoproteome expression by influencing the gut microbiota. PMID:21493887

Evaluation of selenium in dietary supplements using elemental speciation.

PubMed

Kubachka, Kevin M; Hanley, Traci; Mantha, Madhavi; Wilson, Robert A; Falconer, Travis M; Kassa, Zena; Oliveira, Aline; Landero, Julio; Caruso, Joseph

2017-03-01

Selenium-enriched dietary supplements containing various selenium compounds are readily available to consumers. To ensure proper selenium intake and consumer confidence, these dietary supplements must be safe and have accurate label claims. Varying properties among selenium species requires information beyond total selenium concentration to fully evaluate health risk/benefits A LC-ICP-MS method was developed and multiple extraction methods were implemented for targeted analysis of common "seleno-amino acids" and related oxidation products, selenate, selenite, and other species relatable to the quality and/or accuracy of the labeled selenium ingredients. Ultimately, a heated water extraction was applied to recover selenium species from non-selenized yeast supplements in capsule, tablet, and liquid forms. For selenized yeast supplements, inorganic selenium was monitored as a means of assessing selenium yeast quality. A variety of commercially available selenium supplements were evaluated and discrepancies between labeled ingredients and detected species were noted. Published by Elsevier Ltd.

Evaluation of selenium in dietary supplements using elemental speciation

PubMed Central

Kubachka, Kevin M.; Hanley, Traci; Mantha, Madhavi; Wilson, Robert A.; Falconer, Travis M.; Kassa, Zena; Oliveira, Aline; Landero, Julio; Caruso, Joseph

2016-01-01

Selenium-enriched dietary supplements containing various selenium compounds are readily available to consumers. To ensure proper selenium intake and consumer confidence, these dietary supplements must be safe and have accurate label claims. Varying properties among selenium species requires information beyond total selenium concentration to fully evaluate health risk/benefits A LC-ICP-MS method was developed and multiple extraction methods were implemented for targeted analysis of common “seleno-amino acids” and related oxidation products, selenate, selenite, and other species relatable to the quality and/or accuracy of the labeled selenium ingredients. Ultimately, a heated water extraction was applied to recover selenium species from non-selenized yeast supplements in capsule, tablet, and liquid forms. For selenized yeast supplements, inorganic selenium was monitored as a means of assessing selenium yeast quality. A variety of commercially available selenium supplements were evaluated and discrepancies between labeled ingredients and detected species were noted. PMID:27719915

Selenium metabolite levels in human urine after dosing selenium in different chemical forms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasunuma, Ryoichi; Tsuda, Morizo; Ogawa, Tadao

1993-11-01

It has been well known that selenium in marine fish such as tuna and swordfish protects the toxicity of methylmercury in vivo. The protective potency might depend on the chemical forms of selenium in the meat of marine fish sebastes and sperm whale. Little has been revealed, however, on the chemical forms of selenium in the meat of these animals or the selenium metabolites in urine, because the amount of the element is very scarce. Urine is the major excretory route for selenium. The chemical forms of urinary selenium may reflect the metabolism of the element. We have developed methodologymore » for analysis of selenium-containing components in human urine. Using this method, we have observed the time courses of excretory levels of urinary selenium components after a single dose of selenium as selenious acid, selenomethionine, trimethylselenonium ion or tuna meat. 14 refs., 6 figs., 1 tab.« less

Selenium uptake by edible oyster mushrooms (Pleurotus sp.) from selenium-hyperaccumulated wheat straw.

PubMed

Bhatia, Poonam; Prakash, Ranjana; Prakash, N Tejo

2013-01-01

In an effort to produce selenium (Se)-fortifying edible mushrooms, five species of oyster mushroom (Pleurotus sp.), were cultivated on Se-rich wheat straw collected from a seleniferous belt of Punjab, India. Total selenium was analyzed in the selenium hyperaccumulated wheat straw and the fruiting bodies. Significantly high levels (p<0.0001) of Se uptake were observed in fruiting bodies of all mushrooms grown on Se-rich wheat straw. To the best of our knowledge, accumulation and quantification of selenium in mushrooms has hitherto not been reported with substrates naturally enriched with selenium. The results demonstrate the potential of selenium-rich agricultural residues as substrates for production of Se-enriched mushrooms and the ability of different species of oyster mushrooms to absorb and fortify selenium. The study envisages potential use of selenium-rich agricultural residues towards cultivation of Se-enriched mushrooms for application in selenium supplementation or neutraceutical preparations.

Extracellular micronutrient levels and pro-/antioxidant status in trauma patients with wound healing disorders: results of a cross-sectional study.

PubMed

Blass, Sandra C; Goost, Hans; Burger, Christof; Tolba, René H; Stoffel-Wagner, Birgit; Stehle, Peter; Ellinger, Sabine

2013-12-05

Disorders in wound healing (DWH) are common in trauma patients, the reasons being not completely understood. Inadequate nutritional status may favor DWH, partly by means of oxidative stress. Reliable data, however, are lacking. This study should investigate the status of extracellular micronutrients in patients with DWH within routine setting. Within a cross-sectional study, the plasma/serum status of several micronutrients (retinol, ascorbic acid, 25-hydroxycholecalciferol, α-tocopherol, β-carotene, selenium, and zinc) were determined in 44 trauma patients with DWH in addition to selected proteins (albumin, prealbumin, and C-reactive protein; CRP) and markers of pro-/antioxidant balance (antioxidant capacity, peroxides, and malondialdehyde). Values were compared to reference values to calculate the prevalence for biochemical deficiency. Correlations between CRP, albumin and prealbumin, and selected micronutrients were analyzed by Pearson's test. Statistical significance was set at P < 0.05. Mean concentrations of ascorbic acid (23.1 ± 15.9 μmol/L), 25-hydroxycholecalciferol (46.2±30.6 nmol/L), β-carotene (0.6 ± 0.4 μmol/L), selenium (0.79±0.19 μmol/L), and prealbumin (24.8 ± 8.2 mg/dL) were relatively low. Most patients showed levels of ascorbic acid (<28 μmol/L; 64%), 25-hydroxycholecalciferol (<50 μmol/L; 59%), selenium (≤ 94 μmol/L; 71%) and β-carotene (<0.9 μmol/L; 86%) below the reference range. Albumin and prealbumin were in the lower normal range and CRP was mostly above the reference range. Plasma antioxidant capacity was decreased, whereas peroxides and malondialdehyde were increased compared to normal values. Inverse correlations were found between CRP and albumin (P < 0.05) and between CRP and prealbumin (P < 0.01). Retinol (P < 0.001), ascorbic acid (P < 0.01), zinc (P < 0.001), and selenium (P < 0.001) were negatively correlated with CRP. Trauma patients with DWH frequently suffer from protein malnutrition and reduced plasma concentrations of several micronutrients probably due to inflammation, increased requirement, and oxidative burden. Thus, adequate nutritional measures are strongly recommended to trauma patients.

Methylmercury chloride and selenomethionine interactions on health and reproduction in mallards

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.

1998-01-01

Adult mallards (Anas platyrhynchos) were fed a control diet or diets containing 10 ppm mercury as methylmercury chloride, 10 ppm selenium as seleno-DL-methionine, or 10 ppm mercury plus 10 ppm selenium. One of 12 adult males fed 10 ppm mercury died and 8 others suffered from paralysis of their legs by the time the study was terminated. However, when the diet contained 10 ppm selenium in addition to the 10 ppm mercury, none of 12 males became sick. In contrast to the protective effect of selenium against mercury poisoning in males, selenium plus mercury was worse than selenium or mercury alone for some measurements of reproductive success. Both selenium and mercury lowered duckling production through reductions in hatching success and survival of ducklings, but the combination of mercury plus selenium was worse than either mercury or selenium alone. Controls produced an average of 7.6 young per female, females fed 10 ppm selenium produced an average of 2.8 young, females fed 10 ppm mercury produced 1.1 young, and females fed both mercury and selenium produced 0.2 young. Teratogenic effects also were worse for the combined mercury plus selenium treatment; deformities were recorded in 6.1% of the embryos of controls, 16.4% for methylmercury chloride, 36.2% for selenomethionine, and 73.4% for the combination of methylmercury chloride and selenomethionine. The presence of methylmercury in the diet greatly enhanced the storage of selenium in tissues. The livers of males fed 10 ppm selenium contained a mean of 9.6 ppm selenium, whereas the livers of males fed 10 ppm selenium plus 10 ppm mercury contained a mean of 114 ppm selenium. However, selenium did not enhance the storage of mercury. The results show that mercury and selenium may be antagonistic to each other for adults and synergistic to young, even within the same experiment.

Selenium content of foods purchased or produced in Ohio.

PubMed

Snook, J T; Kinsey, D; Palmquist, D L; DeLany, J P; Vivian, V M; Moxon, A L

1987-06-01

Approximately 450 samples of about 100 types of foods consumed by rural and urban Ohioans were analyzed for selenium. Meat, dairy products, eggs, and grain products produced in Ohio have considerably lower selenium content than corresponding products produced in high selenium areas, such as South Dakota. Retail Ohio foods with interregional distribution tended to be higher in selenium content than corresponding foods produced in Ohio. Best sources of selenium in Ohio foods commonly consumed were meat and pasta products. Poor sources of selenium were fruits, most vegetables, candies, sweeteners, and alcoholic and nonalcoholic beverages. Establishment of an accurate data base for selenium depends on knowledge of the interregional distribution of foods, the selenium content of foods at their production site, and the selenium content of foods with wide local distribution.

Association of selenium status and blood glutathione concentrations in blacks and whites

PubMed Central

Richie, John P.; Muscat, Joshua E.; Ellison, Irina; Calcagnotto, Ana; Kleinman, Wayne; El-Bayoumy, Karam

2011-01-01

Selenium deficiency has been linked with increased cancer risk and, in some studies, selenium supplementation was protective against certain cancers. Previous studies suggest that selenium chemoprevention may involve reduced oxidative stress through enhanced glutathione (GSH). Our objectives were to examine the relationships between selenium and GSH in blood and modifying effects of race and sex in free living adults and individuals supplemented with selenium. Plasma selenium concentrations and free and bound GSH concentrations and γ-glutamyl cysteine ligase (GCL) activity in blood were measured in 336 healthy adults, (161 blacks, 175 whites). Plasma selenium and blood GSH were also measured in 36 healthy men from our previously conducted placebo-controlled trial of selenium-enriched yeast (247 μg/day for 9 months). In free-living adults, selenium concentrations were associated with increased blood GSH concentration and GCL activity (P<0.05). Further, selenium was significantly higher in whites than in blacks (P<0.01). After 9 months of supplementation, plasma selenium was increased 114% in whites and 50% in blacks (P<0.05) and blood GSH was increased 35% in whites (P<0.05) but was unchanged in blacks. These results indicate a direct association between selenium and GSH in blood of both free-living and selenium-supplemented individuals, with race being an important modifying factor. PMID:21462082

Updates on clinical studies of selenium supplementation in radiotherapy

PubMed Central

2014-01-01

To establish guidelines for the selenium supplementation in radiotherapy we assessed the benefits and risks of selenium supplementation in radiotherapy. Clinical studies on the use of selenium in radiotherapy were searched in the PubMed electronic database in January 2013. Sixteen clinical studies were identified among the 167 articles selected in the initial search. Ten articles were observational studies, and the other 6 articles reported studies on the effects of selenium supplementation in patients with cancer who underwent radiotherapy. The studies were conducted worldwide including European, American and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium levels were common parameters used to assess the effects of radiotherapy and the selenium supplementation status. Selenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200–500 μg/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of selenium supplementation. PMID:24885670

Selenium Homeostasis and Clustering of Cardiovascular Risk Factors: A Systematic Review.

PubMed

Gharipour, Mojgan; Sadeghi, Masoumeh; Behmanesh, Mehrdad; Salehi, Mansour; Nezafati, Pouya; Gharpour, Amin

2017-10-23

  Selenium is a trace element required for a range of cellular functions. It is widely used for the biosynthesis of the unique amino acid selenocysteine [Sec], which is a structural element of selenoproteins. This systematic review focused on the possible relation between selenium and metabolic risk factors. The literature was searched via PubMed, Scopus, ISI Web of Science, and Google Scholar. Searches were not restricted by time or language. Relevant studies were selected in three phases. After an initial quality assessment, two reviewers extracted all the relevant data, whereas the third reviewer checked their extracted data. All evidence came from experimental and laboratory studies. Selenoprotein P is the best indicator for selenium nutritional levels. In addition, high levels of selenium may increase the risk of metabolic syndrome while the lack of sufficient selenium may also promote metabolic syndrome. selenium supplementation in subjects with sufficient serum selenium levels has a contrary effect on blood pressure, LDL, and total cholesterol. According to the bioavailability of different types of selenium supplementation such as selenomethionine, selenite and selenium-yeast, it seems that the best nutritional type of selenium is selenium-yeast. Regarding obtained results of longitudinal studies and randomized controlled trials, selenium supplementation should not be recommended for primary or secondary cardio-metabolic risk prevention in populations with adequate selenium status.

BindML/BindML+: Detecting Protein-Protein Interaction Interface Propensity from Amino Acid Substitution Patterns.

PubMed

Wei, Qing; La, David; Kihara, Daisuke

2017-01-01

Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .

Imparting albumin-binding affinity to a human protein by mimicking the contact surface of a bacterial binding protein.

PubMed

Oshiro, Satoshi; Honda, Shinya

2014-04-18

Attachment of a bacterial albumin-binding protein module is an attractive strategy for extending the plasma residence time of protein therapeutics. However, a protein fused with such a bacterial module could induce unfavorable immune reactions. To address this, we designed an alternative binding protein by imparting albumin-binding affinity to a human protein using molecular surface grafting. The result was a series of human-derived 6 helix-bundle proteins, one of which specifically binds to human serum albumin (HSA) with adequate affinity (KD = 100 nM). The proteins were designed by transferring key binding residues of a bacterial albumin-binding module, Finegoldia magna protein G-related albumin-binding domain (GA) module, onto the human protein scaffold. Despite 13-15 mutations, the designed proteins maintain the original secondary structure by virtue of careful grafting based on structural informatics. Competitive binding assays and thermodynamic analyses of the best binders show that the binding mode resembles that of the GA module, suggesting that the contacting surface of the GA module is mimicked well on the designed protein. These results indicate that the designed protein may act as an alternative low-risk binding module to HSA. Furthermore, molecular surface grafting in combination with structural informatics is an effective approach for avoiding deleterious mutations on a target protein and for imparting the binding function of one protein onto another.

Mobilization of selenium from the Mancos Shale and associated soils in the lower Uncompahgre River Basin, Colorado

USGS Publications Warehouse

Mast, M. Alisa; Mills, Taylor J.; Paschke, Suzanne S.; Keith, Gabrielle; Linard, Joshua I.

2014-01-01

This study investigates processes controlling mobilization of selenium in the lower part of the Uncompahgre River Basin in western Colorado. Selenium occurs naturally in the underlying Mancos Shale and is leached to groundwater and surface water by limited natural runoff, agricultural and domestic irrigation, and leakage from irrigation canals. Soil and sediment samples from the study area were tested using sequential extractions to identify the forms of selenium present in solid phases. Selenium speciation was characterized for nonirrigated and irrigated soils from an agricultural site and sediments from a wetland formed by a leaking canal. In nonirrigated areas, selenium was present in highly soluble sodium salts and gypsum. In irrigated soils, soluble forms of selenium were depleted and most selenium was associated with organic matter that was stable under near-surface weathering conditions. Laboratory leaching experiments and geochemical modeling confirm that selenium primarily is released to groundwater and surface water by dissolution of highly soluble selenium-bearing salts and gypsum present in soils and bedrock. Rates of selenium dissolution determined from column leachate experiments indicate that selenium is released most rapidly when water is applied to previously nonirrigated soils and sediment. High concentrations of extractable nitrate also were found in nonirrigated soils and bedrock that appear to be partially derived from weathered organic matter from the shale rather than from agricultural sources. Once selenium is mobilized, dissolved nitrate derived from natural sources appears to inhibit the reduction of dissolved selenium leading to elevated concentrations of selenium in groundwater. A conceptual model of selenium weathering is presented and used to explain seasonal variations in the surface-water chemistry of Loutzenhizer Arroyo, a major tributary contributor of selenium to the lower Uncompahgre River.

Selenium Supplementation Affects Insulin Resistance and Serum hs-CRP in Patients with Type 2 Diabetes and Coronary Heart Disease.

PubMed

Farrokhian, A; Bahmani, F; Taghizadeh, M; Mirhashemi, S M; Aarabi, M H; Raygan, F; Aghadavod, E; Asemi, Z

2016-04-01

To our knowledge, this study is the first indicating the effects of selenium supplementation on metabolic status of patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This study was conducted to evaluate the effects of selenium supplementation on metabolic profiles, biomarkers of inflammation, and oxidative stress of patients with T2DM and CHD. This randomized, double-blind, placebo-controlled trial was performed among 60 patients with T2DM and CHD aged 40-85 years. Participants were randomly divided into 2 groups. Group A received 200 μg selenium supplements (n=30) and group B received placebo per day (n=30) for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify metabolic profiles. After 8 weeks, compared with the placebo, selenium supplementation resulted in a significant decrease in serum insulin levels (- 2.2±4.6 vs. + 3.6±8.4 μIU/ml, p=0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (- 0.7±1.3 vs. + 0.9±2.4, p=0.004), homeostatic model assessment-beta cell function (HOMA-B) (- 7.5±17.2 vs. + 15.1±34.5, p=0.002) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (+0.01±0.03 vs. - 0.01±0.03, p=0.02). In addition, patients who received selenium supplements had a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (- 1 372.3±2 318.8 vs. - 99.8±1 453.6 ng/ml, p=0.01) and a significant rise in plasma total antioxidant capacity (TAC) concentrations (+ 301.3±400.6 vs. - 127.2±428.0 mmol/l, p<0.001) compared with the placebo. A 200 μg/day selenium supplementation among patients with T2DM and CHD resulted in a significant decrease in insulin, HOMA-IR, HOMA-B, serum hs-CRP, and a significant increase in QUICKI score and TAC concentrations. © Georg Thieme Verlag KG Stuttgart · New York.

Metabolic and immune response of young turkeys originating from parent flocks fed diets with inorganic or organic selenium.

PubMed

Jankowski, J; Zduńczyk, Z; Sartowska, K; Tykałowski, B; Stenzel, T; Wróblewska, M; Koncicki, A

2011-01-01

The aim of this study was to verify the hypothesis that the health and growth of turkey poults may be improved by supplementing diets fed to parent flocks with available selenium. Experimental poults originated from parent flocks fed with diets containing 0.3 mg/kg inorganic selenium (control group Se(M)) and organic selenium (experimental group Se(O)). Egg yolk selenium content was comparable in both flocks (0.72 and 0.70 mg/kg d.m., respectively). Eggs from the Se(O) flock had a significantly lower content of thiobarbituric acid reactive substances - TBARS (31.13 vs. 53.10 nmol/g, p > 0.001). Se(O) group poults were characterized by higher activity of glutathione peroxidase (7.54 vs. 5.92 U/mL, P = 0.001) and superoxide dismutase (89.30 vs. 79.23 U/mL, P = 0.026). The thigh muscles of Se(O) group birds had significantly higher selenium concentrations (0.74 vs. 0.57, p = 0.045) and a significantly lower TBARS content (38.42 vs. 65.01, p = 0.001). No differences were found between the groups with respect to the content of total protein, albumins and uric acid, and the activites of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (DLH) in day-old poults. On day 28, groups Se(O) and Se(M) differed in the activity of ALT (20.50 vs. 26.33, p = 0.05) and SOD (87.29 vs. 100.02 U/mL, p = 0.035). There were no differences between the groups regarding the percentages of T lymphocyte subpopulations CD4+, CD8+, CD4+CD8+ and B lymphocyte subpopulations (IgM+) at 1 and 28 days of age. Over the experimental period, mortality rates were similar in both groups (7.32 and 8.87%), and so were the final body weights of birds (1108 vs. 1135 g). The results of the study show that the dietary supplementation of organic selenium in turkey parent flocks reduces the rate of oxidation processes in the egg and in the tissues of newly-hatched poults, yet it has no effect on the analyzed parameters of cell-mediated immunity and the growth performance of birds during the first five weeks of their life.

Selenium deficiency and the effects of supplementation on preterm infants

PubMed Central

Freitas, Renata Germano B. O. N.; Nogueira, Roberto José N.; Antonio, Maria Ângela R. G. M.; Barros-Filho, Antonio de Azevedo; Hessel, Gabriel

2014-01-01

Objective: This study aimed to review the literature about blood concentrations of selenium associated with gestational age, feeding, supplementation and related clinical features in preterm infants. Data sources: Systematic review in the following databases: MEDLINE, PubMed, Google academics, SciELO. org, ScienceDirect (Elsevier) and CINAHL-Plus with Full Text (EBSCO). Articles published up to January 2013 with the keywords "selenium deficiency", "selenium supplementation", "neonates", "infants", "newborn" and "preterm infants" were selected. Data synthesis: The studies reported that low blood selenium levels are associated with increased risk of respiratory diseases. Preterm infants, especially with low birth weight, presented lower selenium levels. Selenium deficiency has also been associated with the use of oral infant formula, enteral and parenteral nutrition (with or without selenium addition). The optimal dose and length of selenium supplementation is not well-established, since they are based only on age group and selenium ingestion by breastfed children. Furthermore, the clinical status of the infant affected by conditions that may increase oxidative stress, and consequently, selenium requirements is not taken into account. Conclusions: Prematurity and low birth weight can contribute to low blood selenium in premature infants. Selenium supplementation seems to minimize or prevent clinical complications caused by prematurity. PMID:24676200

Binding of a cyclic organoselenium compound with gold nanoparticles (GNP) and its effect on electron transfer properties.

PubMed

Kumar, Pavitra V; Singh, Beena G; Maiti, Nandita; Iwaoka, Michio; Priyadarsini, K Indira

2014-12-15

Binding of a cyclic organoselenium compound, DL-trans-3,4-dihydroxy-1-selenolane (DHSred) with gold nanoparticles (GNP) of different sizes was studied by absorption spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), surface enhanced Raman spectroscopy (SERS) and zeta-potential (ζ) measurements. GNP of different size were synthesized by varying the reaction conditions and their size was determined by DLS and TEM techniques. The absorption spectral data showed red shift in the surface plasmon resonance (SPR) band indicating increase in the size of GNP on binding to DHSred. SERS studies confirmed that the binding of DHSred with GNP is through selenium center with planar orientation of DHSred on the GNP surface. The product of the number of binding sites (n) in GNP and the binding constant (K) was estimated for GNP of different particle size. The zeta potential (ζ) value of GNP decreased marginally in the presence of DHSred. Further, the binding of DHSred with GNP was found to enhance its reactivity with 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS(·-)) and the reactivity increased with decrease in the GNP size. Such enhancement in the reducing ability may have a greater impact on the antioxidant activity of DHSred. Copyright © 2014 Elsevier Inc. All rights reserved.

Retinal Mueller glial cells trigger the hallmark inflammatory process in autoimmune uveitis.

PubMed

Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Gerhards, Hartmut; Ueffing, Marius; Deeg, Cornelia A

2007-06-01

Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.

Functional assignment to JEV proteins using SVM.

PubMed

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP).

Functional assignment to JEV proteins using SVM

PubMed Central

Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep

2008-01-01

Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP). PMID:19052658

Apo And Calcium-Bound Crystal Structures of Alpha-11 Giardin, An Unusual Annexin From 'Giardia Lamblia'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pathuri, P.; Nguyen, E.T.; Svard, S.G.

2007-07-12

Alpha-11 giardin is a member of the multi-gene alpha-giardin family in the intestinal protozoan, Giardia lamblia. This gene family shares an ancestry with the annexin super family, whose common characteristic is calcium-dependent binding to membranes that contain acidic phospholipids. Several alpha giardins are highly expressed during parasite-induced diarrhea in humans. Despite being a member of a large family of proteins, little is known about the function and cellular localization of alpha-11 giardin, although giardins are often associated with the cytoskeleton. It has been shown that Giardia exhibits high levels of alpha-11 giardin mRNA transcript throughout its life cycle; however, constitutivemore » over-expression of this protein is lethal to the parasite. Determining the three-dimensional structure of an alpha-giardin is essential to identifying functional domains shared in the alpha-giardin family. Here we report the crystal structures of the apo and Ca{sup 2+}-bound forms of alpha-11 giardin, the first alpha giardin to be characterized structurally. Crystals of apo and Ca{sup 2+}-bound alpha-11 giardin diffracted to 1.1 angstroms and 2.93 angstroms, respectively. The crystal structure of selenium-substituted apo alpha-11 giardin reveals a planar array of four tandem repeats of predominantly {alpha}-helical domains, reminiscent of previously determined annexin structures, making this the highest-resolution structure of an annexin to date. The apo alpha-11 giardin structure also reveals a hydrophobic core formed between repeats I/IV and II/III, a region typically hydrophilic in other annexins. Surprisingly, the Ca{sup 2+}-bound structure contains only a single calcium ion, located in the DE loop of repeat I and coordinated differently from the two types of calcium sites observed in previous annexin structures. The apo and Ca{sup 2+}-bound alpha-11 giardin structures assume overall similar conformations; however, Ca2+-bound alpha-11 giardin crystallized in a lower-symmetry space group with four molecules in the asymmetric unit. Vesicle-binding studies suggest that alpha-11 giardin, unlike most other annexins, does not bind to vesicles composed of acidic phospholipids in a calcium-dependent manner.« less

The Association between Selenium and Lipid Levels: a Longitudinal Study in Rural Elderly Chinese

PubMed Central

Chen, Chen; Jin, Yinlong; Unverzagt, Frederick W.; Cheng, Yibin; Hake, Ann M.; Liang, Chaoke; Ma, Feng; Su, Liqin; Liu, Jingyi; Bian, Jianchao; Li, Ping; Gao, Sujuan

2014-01-01

A protective effect of selenium on lipid levels has been reported in populations with relatively low selenium status. However, recent studies found that high selenium exposure may lead to adverse cardiometabolic effects, particularly in selenium-replete populations. We examined the associations of selenium status with changes in lipid levels in a 7-year follow up of an elderly Chinese cohort including participants from selenium-deplete areas. Study population consisted of 140 elderly Chinese aged 65 or older with nail selenium levels measured at baseline (2003-2005). Lipid concentrations were measured in fasting blood samples collected at baseline and the 7-year follow-up (2010-2012). Analysis of covariance (ANCOVA) models was used to determine the association between baseline selenium status and changes in lipid levels from baseline to follow-up adjusting for other covariates. Mean (±standard deviation) baseline selenium concentration was 0.41±0.2mg/kg. In prospective analysis, we found that individuals in the highest selenium quartile group showed 1.11 SD decrease on total-cholesterol (p<0.001), 0.41 SD increase on HDL-cholesterol (p<0.001) and 0.52 SD decrease on triglyceride after 7 years than those in the lowest selenium quartile group. The similar trends were seen with significant lipids changes in the 2th and 3th quartile groups. Selenium has modestly beneficial effects on blood lipid levels in a population with relatively low selenium status. Our result suggests adequate dietary selenium intake as a potential prevention strategy for lowering lipid levels in selenium deplete populations. PMID:25263027

Selenium in blood, semen, seminal plasma and spermatozoa of stallions and its relationship to sperm quality.

PubMed

Bertelsmann, H; Keppler, S; Höltershinken, M; Bollwein, H; Behne, D; Alber, D; Bukalis, G; Kyriakopoulos, A; Sieme, H

2010-01-01

The essential trace element selenium is indispensable for male fertility in mammals. Until now, little data existed regarding the relationship between selenium and sperm quality in the stallion. Selenium, or selenium-dependent glutathione peroxidase activity, was determined in red blood cells, semen, seminal plasma and spermatozoa, and the percentages of spermatozoa with progressive motility (PMS), intact membranes (PMI), altered (positive) acrosomal status (PAS) and detectable DNA damage, determined by the sperm chromatin structure assay, were evaluated in 41 healthy stallions (three samples each). The pregnancy rate per oestrus cycle (PRC) served as an estimation of fertility. An adverse effect on stallion fertility caused by low dietary selenium intake was excluded, as all stallions had sufficient selenium levels in their blood. Interestingly, no significant correlations (P > 0.05) between the selenium level in blood and the selenium level in seminal plasma or spermatozoa were found, suggesting that the selenium level in blood is no indicator of an adequate selenium supply for spermatogenesis. The selenium level in spermatozoa (nmol billion(-1)) was correlated with PMI, PMS and PAS (r = 0.40, r = 0.31 and r = -0.42, respectively; P

Impact of heat treatment on size, structure, and bioactivity of elemental selenium nanoparticles

PubMed Central

Zhang, Jinsong; Taylor, Ethan W; Wan, Xiaochun; Peng, Dungeng

2012-01-01

Background Elemental selenium nanoparticles have emerged as a novel selenium source with the advantage of reduced risk of selenium toxicity. The present work investigated whether heat treatment affects the size, structure, and bioactivity of selenium nanoparticles. Methods and results After a one-hour incubation of solution containing 80 nm selenium particles in a 90°C water bath, the nanoparticles aggregated into larger 110 nm particles and nanorods (290 nm × 70 nm), leading to significantly reduced bioavailability and phase II enzyme induction in selenium-deficient mice. When a solution containing 40 nm selenium nanoparticles was treated under the same conditions, the nanoparticles aggregated into larger 72 nm particles but did not transform into nanorods, demonstrating that the thermostability of selenium nanoparticles is size-dependent, smaller selenium nanoparticles being more resistant than larger selenium nanoparticles to transformation into nanorods during heat treatment. Conclusion The present results suggest that temperature and duration of the heat process, as well as the original nanoparticle size, should be carefully selected when a solution containing selenium nanoparticles is added to functional foods. PMID:22359458

Selenium: a brief review and a case report of selenium responsive cardiomyopathy

PubMed Central

2013-01-01

Background The authors review the role of selenium and highlight possible low selenium levels in soil that may result in deficient states in Saudi Arabia. Case presentation The authors report a case of selenium-responsive cardiomyopathy in a 15-month old Saudi Arabian boy. This case of selenium deficiency causing dilated cardiomyopathy is presented with failure to thrive, prolonged fever and respiratory distress. The investigations revealed selenium deficiency. Selenium supplementation along with anti-failure therapy [Furosimide, Captopril] was administered for 6 months. Following therapy the cardiac function, hair, skin and the general health of the patient improved significantly. Conclusion The patient with dilated cardiomyopathy of unknown etiology, not responding to usual medication may be deficient in selenium. Serum selenium measurements should be included in the diagnostic work-up to ensure early detection and treatment of the disease. The selenium level in the Saudi population needs be determined. Vulnerable populations have to undergo regular selenium measurements and supplementation if indicated. Dependence on processed foods suggests that the Saudi population fortify themselves with nutrient and micronutrient supplements in accordance to the RDA. PMID:23530936

Mechanism of Selenium Loss in Copper Slag

NASA Astrophysics Data System (ADS)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-03-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

Mechanism of Selenium Loss in Copper Slag

NASA Astrophysics Data System (ADS)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-06-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

A Better Understanding of Protein Structure and Function by the Synthesis and Incorporation of Selenium- and Tellurium Containing Tryptophan Analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmey, Sherif Samir; Rice, Ambrose Eugene; Hatch, Duane Michael

Unnatural heavy metal-containing amino acid analogs have shown to be very important in the analysis of protein structure, using methods such as X-ray crystallography, mass spectroscopy, and NMR spectroscopy. Synthesis and incorporation of selenium-containing methionine analogs has already been shown in the literature however with some drawbacks due to toxicity to host organisms. Thus synthesis of heavy metal tryptophan analogs should prove to be more effective since the amino acid tryptophan is naturally less abundant in many proteins. For example, bioincorporation of β-seleno[3,2-b]pyrrolyl-L-alanine ([4,5]SeTrp) and β-selenolo[2,3-b]pyrrolyl-L-alanine ([6,7]SeTrp) has been shown in the following proteins without structural or catalytic perturbations: humanmore » annexin V, barstar, and dihydrofolate reductase. The reported synthesis of these Se-containing analogs is currently not efficient for commercial purposes. Thus a more efficient, concise, high-yield synthesis of selenotryptophan, as well as the corresponding, tellurotryptophan, will be necessary for wide spread use of these unnatural amino acid analogs. This research will highlight our progress towards a synthetic route of both [6,7]SeTrp and [6,7]TeTrp, which ultimately will be used to study the effect on the catalytic activity of Lignin Peroxidase (LiP).« less

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

Reproduction in mallards fed selenium

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.; Krynitsky, A.J.; Weller, D.M.G.

1987-01-01

Mallards (Anas platyrhynchos) were fed diets containing 1, 5, 10, 25 or 100 ppm selenium as sodium selenite, a diet containing 10 ppm selenium as seleno-DL-methionine or a control diet. There were no effects of 1, 5 or 10 ppm selenium as sodium selenite on either weight or survival of adults or on reproductive success, and there did not appear to be a dose-response relationship at these lower levels. The 100 ppm selenium diet killed 11 of 12 adults; one adult male fed 25 ppm selenium died. Selenium at 25 and 100 ppm caused weight loss in adults. Females fed 25 ppm selenium took longer to begin laying eggs and intervals between eggs were longer than in females in other treatment groups. Hatching success appeared to be reduced in birds fed 10 ppm selenium at selenomethionine, but the reduction was not statistically significant. The survival of ducklings and the mean number of 21-d-old ducklings produced per female were reduced in the 25 ppm selenium as sodium selenite group and the 10 ppm selenium as selenomethionine group. Egg weights were not affected by any selenium treatment, but 25 ppm selenium lowered the Ratcliffe Index. Duckling weights at hatching and at 21 d of age were reduced 28 and 36%, respectively, in birds fed 25 ppm selenium, as compared with controls. Body weights measured on day 21 were lower for ducklings fed 10 ppm selenium as selenomethionine than in some other groups. Selenium in concentrations of 10 and 25 ppm as sodium selenite caused mainly embryotoxic effects, whereas 10 ppm as selenomethionine was more teratogenic, causing hydrocephaly, bill defects, eye defects (microphthalmia and anophthalmia) and foot and toe defects, including ectrodactyly. Selenomethionine was much more readily taken up by mallards and passed into their eggs than was sodium selenite, and a greater proportion of the selenium in the eggs ended up in the white when selenomethionine was fed. Adult males accumulated more selenium than did females, probably because of the females' ability to eliminate selenium in their eggs.

Toxicity of organic and inorganic selenium to mallard ducklings

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.; Gold, L.G.

1988-01-01

The toxicity of selenomethionine and sodium selenite to mallard ducklings (Anas platyrhynchos) was measured by feeding each form from hatching to six weeks of age at dietary concentrations of 0, 10, 20, 40, and 80 ppm selenium. At 80 ppm selenium, sodium selenite caused 97.5% mortality by six weeks and selenomethionine caused 100% mortality. At 40 ppm, these two forms of selenium caused 25 and 12.5% mortality. No mortality occurred at 10 or 20 ppm. Diets containing 20, 40, or 80 ppm selenium in both forms caused decreases in food consumption and growth. The only statistically significant effect of 10 ppm selenium was with sodium selenite, which resulted in larger livers than controls. Selenomethionine was more readily stored in the liver than sodium selenite at levels above 10 ppm selenium in the diet. Based on comparisons of residues of selenium in livers of surviving and dead ducklings, concentrations in the liver were not diagnostic of death due to selenium poisoning. Because both forms of selenium resulted in severe reductions in food consumption, selenium-induced starvation may have been related to duckling mortality. It was not clear whether either form of selenium at 10 ppm in the diet resulted in a leveling off of selenium concentrations in the liver within six weeks.

Antioxidant Intake and Pancreatic Cancer Risk: the VITamins And Lifestyle (VITAL) Study

PubMed Central

Han, Xuesong; Li, Jingjing; Brasky, Theodore M.; Xun, Pengcheng; Stevens, June; White, Emily; Gammon, Marilie D.; He, Ka

2012-01-01

Background Oxidative stress causes damage to many components of human cells (i.e., proteins, lipids, and DNA) and is involved in carcinogenesis. Nutrients with antioxidant properties may protect against oxidative stress. We examined intake of antioxidants from diet and supplements in relation to pancreatic cancer risk among participants of the VITamins And Lifestyle (VITAL) Study. Methods Participants were 77,446 men and women, ages 50–76 years, who were residents of western Washington State and completed a baseline questionnaire between 2000 and 2002. Participants reported usual diet over the past year and use of supplements over the past 10 years, in addition to demographic and lifestyle factors. During a median follow-up of 7.1 years, 184 participants developed pancreatic adenocarcinoma. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for seven antioxidants: β-carotene, lutein and zeaxanthin, lycopene, vitamin C, vitamin E, selenium and zinc. Results We observed an inverse association between dietary selenium and pancreatic cancer risk (medium vs. low intake: HR 0.58, 95% CI 0.35–0.94; high vs. low intake: HR 0.44, 95% CI 0.23–0.85; p-trend = 0.01); however, when supplemental and dietary exposures were combined, the association was no longer statistically significant. Conclusions Dietary selenium intake is inversely associated with risk of pancreatic cancer and the observed association is attenuated by selenium supplementation. PMID:23280534

Treatment strategies in Alzheimer's disease: a review with focus on selenium supplementation.

PubMed

Aaseth, Jan; Alexander, Jan; Bjørklund, Geir; Hestad, Knut; Dusek, Petr; Roos, Per M; Alehagen, Urban

2016-10-01

Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

Thioredoxin binding protein (TBP)-2/Txnip and α-arrestin proteins in cancer and diabetes mellitus.

PubMed

Masutani, Hiroshi; Yoshihara, Eiji; Masaki, So; Chen, Zhe; Yodoi, Junji

2012-01-01

Thioredoxin binding protein -2/ thioredoxin interacting protein is an α-arrestin protein that has attracted much attention as a multifunctional regulator. Thioredoxin binding protein -2 expression is downregulated in tumor cells and the level of thioredoxin binding protein is correlated with clinical stage of cancer. Mice with mutations or knockout of the thioredoxin binding protein -2 gene are much more susceptible to carcinogenesis than wild-type mice, indicating a role for thioredoxin binding protein -2 in cancer suppression. Studies have also revealed roles for thioredoxin binding protein -2 in metabolic control. Enhancement of thioredoxin binding protein -2 expression causes impairment of insulin sensitivity and glucose-induced insulin secretion, and β-cell apoptosis. These changes are important characteristics of type 2 diabetes mellitus. Thioredoxin binding protein -2 regulates transcription of metabolic regulating genes. Thioredoxin binding protein -2-like inducible membrane protein/ arrestin domain containing 3 regulates endocytosis of receptors such as the β(2)-adrenergic receptor. The α-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Elucidation of the molecular mechanisms of α-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus.

A Single Rainbow Trout Cobalamin-binding Protein Stands in for Three Human Binders

PubMed Central

Greibe, Eva; Fedosov, Sergey; Sorensen, Boe S.; Højrup, Peter; Poulsen, Steen S.; Nexo, Ebba

2012-01-01

Cobalamin uptake and transport in mammals are mediated by three cobalamin-binding proteins: haptocorrin, intrinsic factor, and transcobalamin. The nature of cobalamin-binding proteins in lower vertebrates remains to be elucidated. The aim of this study was to characterize the cobalamin-binding proteins of the rainbow trout (Oncorhynchus mykiss) and to compare their properties with those of the three human cobalamin-binding proteins. High cobalamin-binding capacity was found in trout stomach (210 pmol/g), roe (400 pmol/g), roe fluid (390 nmol/liter), and plasma (2500 nmol/liter). In all cases, it appeared to be the same protein based on analysis of partial sequences and immunological responses. The trout cobalamin-binding protein was purified from roe fluid, sequenced, and further characterized. Like haptocorrin, the trout cobalamin-binding protein was stable at low pH and had a high binding affinity for the cobalamin analog cobinamide. Like haptocorrin and transcobalamin, the trout cobalamin-binding protein was present in plasma and recognized ligands with altered nucleotide moiety. Like intrinsic factors, the trout cobalamin-binding protein was present in the stomach and resisted degradation by trypsin and chymotrypsin. It also resembled intrinsic factor in the composition of conserved residues in the primary cobalamin-binding site in the C terminus. The trout cobalamin-binding protein was glycosylated and displayed spectral properties comparable with those of haptocorrin and intrinsic factor. In conclusion, only one soluble cobalamin-binding protein was identified in the rainbow trout, a protein that structurally behaves like an intermediate between the three human cobalamin-binding proteins. PMID:22872637

Selenium

USGS Publications Warehouse

Stillings, Lisa L.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

2017-12-19

Selenium (Se) was discovered in 1817 in pyrite from copper mines in Sweden. It is a trace element in Earth’s crust, with an abundance of three to seven orders of magnitude less than the major rock-forming elements. Commercial use of selenium began in the United States in 1910, when it was used as a pigment for paints, ceramic glazes, and red glass. Since that time, it has had many other economic uses—notably, in the 1930s and 1940s, when it was used in rectifiers (which change alternating current to direct current), and in the 1960s, when it began to be used in the liner of photocopier drums. In the 21st century, other compounds have replaced selenium in these older products; modern uses for selenium include energy-efficient windows that limit heat transfer and thin-film photovoltaic cells that convert solar energy into electricity.In Earth’s crust, selenium is found as selenide minerals, selenate and selenite salts, and as substitution for sulfur in sulfide minerals. It is the sulfide minerals, most commonly those in porphyry copper deposits, that provide the bulk of the selenium produced for the international commodity market. Selenium is obtained as a byproduct of copper refining and recovered from the anode slimes generated in electrolytic production of copper. Because of this, the countries that have the largest resources and (or) reserves of copper also have the largest resources and (or) reserves of selenium.Because selenium occurs naturally in Earth’s crust, its presence in air, water, and soil results from both geologic reactions and human activity. Selenium is found concentrated naturally in soils that overlie bedrock with high selenium concentrations. Selenium mining, processing, use in industrial and agricultural applications, and disposal may all contribute selenium to the environment. A well-known case of selenium contamination from agricultural practices was discovered in 1983 in the Kesterson National Wildlife Refuge in California. There, waters draining from agricultural fields created wetlands with high concentrations of dissolved selenium in the water. The selenium was taken up by aquatic wildlife and caused massive numbers of embryonic deformities and deaths.Regulatory agencies have since worked to safeguard ecological and human health by creating environmental exposure guidelines based upon selenium concentrations in water and in fish tissue. Any attempt to regulate selenium concentrations requires a delicate balance because selenium occurs naturally and is also a vital nutrient for the health of wildlife, domestic stock, and humans. Selenium is commonly added as a vitamin to animal feed, and in some regions of the United States and the world, it is added as an amendment to soils for uptake by agricultural crops.The important role of selenium in economic products, energy supply, agriculture, and health will continue for well into the future. The challenge to society is to balance the benefits of selenium use with the environmental consequences of its extraction. Increased understanding of the elemental cycle of selenium in the earth may lead to new (or unconventional) sources of selenium, the discovery of new methods of extraction, and new technologies for minimizing the transfer of selenium from rock to biota, so to protect environmental and human health.

Selenium concentration and speciation in biofortified flour and bread: Retention of selenium during grain biofortification, processing and production of Se-enriched food.

PubMed

Hart, D J; Fairweather-Tait, S J; Broadley, M R; Dickinson, S J; Foot, I; Knott, P; McGrath, S P; Mowat, H; Norman, K; Scott, P R; Stroud, J L; Tucker, M; White, P J; Zhao, F J; Hurst, R

2011-06-15

The retention and speciation of selenium in flour and bread was determined following experimental applications of selenium fertilisers to a high-yielding UK wheat crop. Flour and bread were produced using standard commercial practices. Total selenium was measured using inductively coupled plasma-mass spectrometry (ICP-MS) and the profile of selenium species in the flour and bread were determined using high performance liquid chromatography (HPLC) ICP-MS. The selenium concentration of flour ranged from 30ng/g in white flour and 35ng/g in wholemeal flour from untreated plots up to >1800ng/g in white and >2200ng/g in wholemeal flour processed from grain treated with selenium (as selenate) at the highest application rate of 100g/ha. The relationship between the amount of selenium applied to the crop and the amount of selenium in flour and bread was approximately linear, indicating minimal loss of Se during grain processing and bread production. On average, application of selenium at 10g/ha increased total selenium in white and wholemeal bread by 155 and 185ng/g, respectively, equivalent to 6.4 and 7.1μg selenium per average slice of white and wholemeal bread, respectively. Selenomethionine accounted for 65-87% of total extractable selenium species in Se-enriched flour and bread; selenocysteine, Se-methylselenocysteine selenite and selenate were also detected. Controlled agronomic biofortification of wheat crops for flour and bread production could provide an appropriate strategy to increase the intake of bioavailable selenium. Copyright © 2010 Elsevier Ltd. All rights reserved.

PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, So-Hee; Moon, Jeonghee; Lee, Myungkyu

2013-09-13

Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified asmore » a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1.« less

Volatilization of selenium from astragalus plants irrigated with selenium-laden water. Open file report

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacDonald, D.J.; Lujan, M.J.; Ary, T.S.

1989-01-01

Living plants of Astragalus bisulcatus and Atriplex canescens were irrigated with solutions containing selenium to investigate the plants' ability to selectively remove selenium from selenium-contaminated water. The plants were grown from seed in an indoor environment and harvested for analysis at the end of a typical 7-month growing season. Of the total selenium applied to soil in which the plants were grown, only about 1% was incorporated in plant tissues of Astragalus, but approximately 18% of applied selenium was dissipated into the air from the living plants. Atriplex plants did not absorb or dissipate detectable amounts of selenium.

Selenium and its supplementation in cardiovascular disease--what do we know?

PubMed

Benstoem, Carina; Goetzenich, Andreas; Kraemer, Sandra; Borosch, Sebastian; Manzanares, William; Hardy, Gil; Stoppe, Christian

2015-04-27

The trace element selenium is of high importance for many of the body's regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.

Selenium and Its Supplementation in Cardiovascular Disease—What do We Know?

PubMed Central

Benstoem, Carina; Goetzenich, Andreas; Kraemer, Sandra; Borosch, Sebastian; Manzanares, William; Hardy, Gil; Stoppe, Christian

2015-01-01

The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery. PMID:25923656

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

PubMed Central

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2015-01-01

A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

Producing selenium-enriched eggs and meat to improve the selenium status of the general population.

PubMed

Fisinin, Vladimir I; Papazyan, Tigran T; Surai, Peter F

2009-01-01

The role of selenium (Se) in human health and diseases has been discussed in detail in several recent reviews, with the main conclusion being that selenium deficiency is recognised as a global problem which urgently needs resolution. Since selenium content in plant-based food depends on its availability from soil, the level of this element in food and feeds varies among regions. In general, eggs and meat are considered to be good sources of selenium in human diet. When considering ways to improve human selenium intake, there are several potential options. These include direct supplementation, soil fertilisation and supplementation of food staples such as flour, and production of functional foods. Analysing recent publications related to functional food production, it is evident that selenium-enriched eggs can be used as an important delivery system of this trace mineral for humans. In particular, developments and commercialisation of organic forms of selenium have initiated a new era in the availability of selenium-enriched products. It has been shown that egg selenium content can easily be manipulated to give increased levels, especially when organic selenium is included in hens' diet at levels that provide 0.3-0.5 mg/kg selenium in the feed. As a result, technology for the production of eggs delivering approximately 50% (30-35 microg) of the human selenium RDA have been developed and successfully tested. Currently companies all over the world market selenium-enriched eggs including the UK, Ireland, Mexico, Columbia, Malaysia, Thailand, Australia, Turkey, Russia and the Ukraine. Prices for enriched eggs vary from country to country, typically being similar to free-range eggs. Selenium-enriched chicken, pork and beef can also be produced when using organic selenium in the diet of poultry and farm animals. The scientific, technological and other advantages and limitations of producing designer/modified eggs as functional foods are discussed in this review.

How to use the world's scarce selenium resources efficiently to increase the selenium concentration in food

PubMed Central

Haug, Anna; Graham, Robin D.; Christophersen, Olav A.; Lyons, Graham H.

2007-01-01

The world's rare selenium resources need to be managed carefully. Selenium is extracted as a by-product of copper mining and there are no deposits that can be mined for selenium alone. Selenium has unique properties as a semi-conductor, making it of special value to industry, but it is also an essential nutrient for humans and animals and may promote plant growth and quality. Selenium deficiency is regarded as a major health problem for 0.5 to 1 billion people worldwide, while an even larger number may consume less selenium than required for optimal protection against cancer, cardiovascular diseases and severe infectious diseases including HIV disease. Efficient recycling of selenium is difficult. Selenium is added in some commercial fertilizers, but only a small proportion is taken up by plants and much of the remainder is lost for future utilization. Large biofortification programmes with selenium added to commercial fertilizers may therefore be a fortification method that is too wasteful to be applied to large areas of our planet. Direct addition of selenium compounds to food (process fortification) can be undertaken by the food industry. If selenomethionine is added directly to food, however, oxidation due to heat processing needs to be avoided. New ways to biofortify food products are needed, and it is generally observed that there is less wastage if selenium is added late in the production chain rather than early. On these bases we have proposed adding selenium-enriched, sprouted cereal grain during food processing as an efficient way to introduce this nutrient into deficient diets. Selenium is a non-renewable resource. There is now an enormous wastage of selenium associated with large-scale mining and industrial processing. We recommend that this must be changed and that much of the selenium that is extracted should be stockpiled for use as a nutrient by future generations. PMID:18833333

Monoclonal antibodies to human vitamin D-binding protein.

PubMed Central

Pierce, E A; Dame, M C; Bouillon, R; Van Baelen, H; DeLuca, H F

1985-01-01

Monoclonal antibodies to vitamin D-binding protein isolated from human serum have been produced. The antibodies obtained have been shown to be specific for human vitamin D-binding protein by three independent assays. The antibodies recognize human vitamin D-binding protein specifically in an enzyme-linked immunosorbent assay. Human vitamin D-binding protein is detected specifically in both pure and crude samples by a radiometric immunosorbent assay (RISA) and by an immunoprecipitation assay. The anti-human vitamin D-binding protein antibodies cross-react with monkey and pig vitamin D-binding protein, but not with vitamin D-binding protein from rat, mouse, or chicken, as determined by the RISA and immunoprecipitation assays. Images PMID:3936035

Rhizobium selenitireducens proteins involved in the reduction of selenite to elemental selenium

USDA-ARS?s Scientific Manuscript database

Microbial based bioremediation barriers can remove the metalloid selenite (SeO3–2) from flowing groundwater. The organisms associated with the process include microorganisms from within the bacterial and archaeal domains that can reduce soluble SeO3–2 to the insoluble and reddish-colored elemental ...

S-Adenosylmethionine-dependent protein methylation Is required for expression of selenoprotein P and gluconeogenic enzymes in HepG2 human hepatocytes

USDA-ARS?s Scientific Manuscript database

Cellular methylation processes enable expression of gluconeogenic enzymes and metabolism of the nutrient selenium (Se). Se status may relate to type-II diabetes and plasma levels of selenoprotein P (SEPP1) are positively correlated with insulin resistance. Increased expression of gluconeogenic enzym...

Relationship of dietary intake of fish and non-fish selenium to serum lipids in Japanese rural coastal community.

PubMed

Miyazaki, Yukiko; Koyama, Hiroshi; Nojiri, Masami; Suzuki, Shosuke

2002-01-01

Several studies have suggested that dietary selenium deficiency may be associated with an increased risk of coronary heart disease (CHD). In the present study, 55 men and 71 women were selected from participants in a health examination in a rural coastal community in Japan. The mean dietary selenium intake calculated from the simple food frequency questionnaire (SFFQ) was 127.5 micrograms/day. Fish was the major source of dietary selenium and it contributed to 68.7% of the daily total. HDL cholesterol was higher in the middle selenium intake group and in the high selenium intake group than in the low selenium intake group in all subjects and for males, and a significant difference was found between the middle selenium intake group and the low selenium intake group. The atherogenic index was significantly higher in the low selenium intake group than in the middle selenium intake group and in the high selenium intake group in males. GPx activity, total cholesterol and triacylglycerols did not show any significant differences among the three different selenium intake groups. Dietary intake of non-fish Se had a positive correlation with HDL cholesterol, and an inverse correlation with the atherogenic index in all subjects and for females. On the other hand, dietary intake of fish-Se had no relationship with any serum lipids. Non-fish Se is an important factor in selenium status for the prevention of CHD.

Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach.

PubMed

Ghorbel, Imen; Elwej, Awatef; Chaabane, Mariem; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Zeghal, Najiba

2017-03-01

Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl 3 ) (400 ppm) via drinking water, AlCl 3 associated with Na 2 SeO 3 (0.5 mg/kg of diet), or only Na 2 SeO 3 . Exposure of rats to AlCl 3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non-enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin-laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 2. Tissue biochemistry evaluation.

PubMed

Lohner, T W; Reash, R J; Williams, M

2001-11-01

Sunfish were collected from a fly ash pond-receiving stream and an Ohio River reference site to assess biochemical responses to coal ash effluent exposure. Selenium levels in sunfish from the receiving stream were higher than toxic thresholds associated with adverse population effects and reproductive impairment. Tissue biochemistry was found to be indicative of metal exposure and effect, but varied widely. Liver glycogen was positively correlated with increased liver metal levels, indicating no adverse effect upon stored carbohydrate levels. Lipid levels decreased with increasing metals, indicating possible nutritional stress. Protein levels increased with increasing metal levels, possibly due to the synthesis of proteins to sequester the metals. ATPase, dUTPase, and alkaline phosphatase activity generally decreased with exposure to ash pond metals, but remained within normal physiological ranges. Fish condition factors and liver somatic indices were correlated with liver lipid levels, dUTPase activity, and gill ATPase and alkaline phosphatase activity. Exposure to coal ash effluents produced biochemical markers of exposure that were associated with fish condition indicators; however, the indices themselves were not significantly affected by effluent exposure.

Effect of dietary organic selenium on muscle proteolytic activity and water-holding capacity in pork.

PubMed

Calvo, L; Toldrá, F; Aristoy, M C; López-Bote, C J; Rey, A I

2016-11-01

This study evaluates the effect of dietary selenium (Se) supplementation source (organic, Se-enriched yeast; SY vs. inorganic, sodium selenite; SS), dose (0.2: L vs. 0.4: H mg/kg) and the combination of Se and vitamin E (VITE+SS) for 26days on drip loss, TBARS, colour changes, myofibrillar protein pattern and proteolysis in pork. The lowest water losses were observed in the SY-H group when compared to the others. SY-H and VITE+SS groups presented lower myofibrillar protein hydrolysis/oxidation. VITE+SS supplementation also resulted in higher PRO, TRP and PHE content at days 2 and 7, whereas the SY group showed increased GLY and CAR and tended to have higher TAU and ANS at day 2. The myofibrillar fragmentation index was not modified by the dietary treatment; however, at day 8, it tended to be higher in groups supplemented with SeY and VITE+SS. The results of the present study might indicate a possible relation between muscle proteolysis and water loss. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ebselen ameliorates β-amyloid pathology, tau pathology, and cognitive impairment in triple-transgenic Alzheimer's disease mice.

PubMed

Xie, Yongli; Tan, Yibin; Zheng, Youbiao; Du, Xiubo; Liu, Qiong

2017-08-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is clinically characterized by memory loss and cognitive decline caused by protein misfolding and aggregation. Imbalance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of AD. Selenium (Se), a vital trace element with excellent antioxidant potential, is preferentially retained in the brain in Se-limited conditions and has been reported to provide neuroprotection through resisting oxidative damage. In this paper, we studied for the first time the potential of Ebselen, a lipid-soluble selenium compound with GPx-like activity, in the treatment of cognitive dysfunction and neuropathology of triple-transgenic AD (3 × Tg-AD) mice, AD model cell, and primary culture. We demonstrated that Ebselen inhibited oxidative stress in both AD model cells and mouse brains with increasing GPx and SOD activities and meanwhile reduced p38 mitogen-activated protein kinases activities. By decreasing the expression of amyloid precursor protein and β-secretase, Ebselen reduced the levels of Aβ in AD neurons and mouse brains, especially the most toxic oligomeric form. Besides, mislocation of phosphorylated tau in neurons and phosphorylation levels of tau protein at Thr231, Ser396, and Ser404 residues were also inhibited by Ebselen, probably by its regulatory roles in glycogen synthase kinase 3β and protein phosphatase 2A activity. In addition, Ebselen mitigated the decrease of synaptic proteins including synaptophysin and postsynaptic density protein 95 in AD model cells and neurons. Consequently, the spatial learning and memory of 3 × Tg-AD mice were significantly improved upon Ebselen treatment. This study provides a potential novel therapeutic approach for the prevention of AD.

Phosphatidic acid binding proteins display differential binding as a function of membrane curvature stress and chemical properties.

PubMed

Putta, Priya; Rankenberg, Johanna; Korver, Ruud A; van Wijk, Ringo; Munnik, Teun; Testerink, Christa; Kooijman, Edgar E

2016-11-01

Phosphatidic acid (PA) is a crucial membrane phospholipid involved in de novo lipid synthesis and numerous intracellular signaling cascades. The signaling function of PA is mediated by peripheral membrane proteins that specifically recognize PA. While numerous PA-binding proteins are known, much less is known about what drives specificity of PA-protein binding. Previously, we have described the ionization properties of PA, summarized in the electrostatic-hydrogen bond switch, as one aspect that drives the specific binding of PA by PA-binding proteins. Here we focus on membrane curvature stress induced by phosphatidylethanolamine and show that many PA-binding proteins display enhanced binding as a function of negative curvature stress. This result is corroborated by the observation that positive curvature stress, induced by lyso phosphatidylcholine, abolishes PA binding of target proteins. We show, for the first time, that a novel plant PA-binding protein, Arabidopsis Epsin-like Clathrin Adaptor 1 (ECA1) displays curvature-dependence in its binding to PA. Other established PA targets examined in this study include, the plant proteins TGD2, and PDK1, the yeast proteins Opi1 and Spo20, and, the mammalian protein Raf-1 kinase and the C2 domain of the mammalian phosphatidylserine binding protein Lact as control. Based on our observations, we propose that liposome binding assays are the preferred method to investigate lipid binding compared to the popular lipid overlay assays where membrane environment is lost. The use of complex lipid mixtures is important to elucidate further aspects of PA binding proteins. Copyright © 2016. Published by Elsevier B.V.

Tracking metal ions through a Cu/Ag efflux pump assigns the functional roles of the periplasmic proteins

DOE PAGES

Chacon, Kelly N.; Mealman, Tiffany D.; McEvoy, Megan M.; ...

2014-10-13

Copper is an essential nutrient for all aerobic organisms but is toxic in excess. At the host–pathogen interface, macrophages respond to bacterial infection by copper-dependent killing mechanisms, whereas the invading bacteria are thought to counter with an up-regulation of copper transporters and efflux pumps. The tripartite efflux pump CusCBA and its metallochaperone CusF are vital to the detoxification of copper and silver ions in the periplasm of Escherichia coli. However, the mechanism of efflux by this complex, which requires the activation of the inner membrane pump CusA, is poorly understood. In this paper, we use selenomethionine (SeM) active site labelsmore » in a series of biological X-ray absorption studies at the selenium, copper, and silver edges to establish a “switch” role for the membrane fusion protein CusB. We determine that metal-bound CusB is required for activation of cuprous ion transfer from CusF directly to a site in the CusA antiporter, showing for the first time (to our knowledge) the in vitro activation of the Cus efflux pump. This metal-binding site of CusA is unlike that observed in the crystal structures of the CusA protein and is composed of one oxygen and two sulfur ligands. Finally, our results suggest that metal transfer occurs between CusF and apo-CusB, and that, when metal-loaded, CusB plays a role in the regulation of metal ion transfer from CusF to CusA in the periplasm.« less

Tracking metal ions through a Cu/Ag efflux pump assigns the functional roles of the periplasmic proteins.

PubMed

Chacón, Kelly N; Mealman, Tiffany D; McEvoy, Megan M; Blackburn, Ninian J

2014-10-28

Copper is an essential nutrient for all aerobic organisms but is toxic in excess. At the host-pathogen interface, macrophages respond to bacterial infection by copper-dependent killing mechanisms, whereas the invading bacteria are thought to counter with an up-regulation of copper transporters and efflux pumps. The tripartite efflux pump CusCBA and its metallochaperone CusF are vital to the detoxification of copper and silver ions in the periplasm of Escherichia coli. However, the mechanism of efflux by this complex, which requires the activation of the inner membrane pump CusA, is poorly understood. Here, we use selenomethionine (SeM) active site labels in a series of biological X-ray absorption studies at the selenium, copper, and silver edges to establish a "switch" role for the membrane fusion protein CusB. We determine that metal-bound CusB is required for activation of cuprous ion transfer from CusF directly to a site in the CusA antiporter, showing for the first time (to our knowledge) the in vitro activation of the Cus efflux pump. This metal-binding site of CusA is unlike that observed in the crystal structures of the CusA protein and is composed of one oxygen and two sulfur ligands. Our results suggest that metal transfer occurs between CusF and apo-CusB, and that, when metal-loaded, CusB plays a role in the regulation of metal ion transfer from CusF to CusA in the periplasm.

Selenoprotein W expression and regulation in mouse brain and neurons

PubMed Central

Raman, Arjun V; Pitts, Matthew W; Seyedali, Ali; Hashimoto, Ann C; Bellinger, Frederick P; Berry, Marla J

2013-01-01

Background Selenoprotein W (Sepw1) is a selenium-containing protein that is abundant in brain and muscle of vertebrate animals. Muscular expression of Sepw1 is reduced by dietary selenium (Se) deficiency in mammals, whereas brain expression is maintained. However, expression of Sepw1 depends on the Se transporter selenoprotein P (Sepp1). Methods We assessed the regional and cellular expression of Sepw1 in the mouse brain and neuronal cultures. Results We found that Sepw1 is widespread in neurons and neuropil of mouse brain and appears in both the soma and processes of neurons in culture. Pyramidal neurons of cortex and hippocampus express high levels of Sepw1. It is also abundant in Purkinje neurons and their dendritic arbors in the cerebellum. Analysis of synaptosome fractions prepared from mice brains indicated that Sepw1 is present at synapses, as were several proteins involved in selenoprotein synthesis. Synaptic expression of Sepw1 expression is reduced in mice lacking Sepp1 compared with control mice, although selenoprotein synthesis factors were similarly expressed in both genotypes. Lastly, Sepw1 mRNA coimmunoprecipitates with Staufen 2 protein in a human neuronal cell line. Conclusions Our results suggest that Sepw1 may be locally synthesized in distal compartments of neurons including synapses. PMID:24392277

Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

PubMed Central

Joseph, Jacob; Loscalzo, Joseph

2013-01-01

Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease. PMID:23434902

Selenium exposure in subjects living in areas with high selenium concentrated drinking water: results of a French integrated exposure assessment survey.

PubMed

Emmanuelle, Barron; Virginie, Migeot; Fabienne, Séby; Isabelle, Ingrand; Martine, Potin-Gautier; Bernard, Legube; Sylvie, Rabouan

2012-04-01

Selenium is an essential element which can be toxic if ingested in excessive quantities. The main human exposure is food. In addition, intake may be boosted by consumption drinking water containing unusual high selenium concentration. We measured the individual selenium level of people exposed to selenium concentration in drinking water greater than the maximum recommended limit which is 10 μg/L. We carried out a prospective cohort study on 80 adults (40 exposed subjects i.e. living in the involved area and 40 non-exposed ones i.e. living elsewhere) in western France. We used three different approaches: (1) direct measurement of ingested selenium by the duplicate portion method, (2) dietary reconstitution with a food frequency questionnaire (FFQ) and (3) evaluation of the individual selenium status by measuring the selenium content in toenail clippings. Analyses were performed by inductively coupled plasma-mass spectrometry. The association between toenail selenium concentration and area of residence was analyzed using linear regression with repeated measurements. We estimated selenium intake from FFQ at 64±14 μg/day for exposed subjects as opposed to 52±14 μg/day for the non-exposed ones. On the basis of 305 duplicate diet samples, average intake was estimated at 64±26 μg/day for exposed subjects. Area of residence (p=0.0030) and smoking (p=0.0054) were independently associated with toenail selenium concentration. Whatever method used for estimating selenium intake, the selenium level in this studied area with high selenium concentrated drinking water is much lower than in seleniferous areas. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recycling of high purity selenium from CIGS solar cell waste materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gustafsson, Anna M.K., E-mail: anna.gustafsson@chalmers.se; Foreman, Mark R.StJ.; Ekberg, Christian

Highlights: • A new method for recycling of selenium from CIGS solar cell materials is presented. • Separation of selenium as selenium dioxide after heating in oxygen atmosphere. • Complete selenium separation after oxidation of <63 μm particles at 800 °C for 1 h. • After reduction of selenium dioxide the selenium purity was higher than 99.999 wt%. - Abstract: Copper indium gallium diselenide (CIGS) is a promising material in thin film solar cell production. To make CIGS solar cells more competitive, both economically and environmentally, in comparison to other energy sources, methods for recycling are needed. In addition tomore » the generally high price of the material, significant amounts of the metals are lost in the manufacturing process. The feasibility of recycling selenium from CIGS through oxidation at elevated temperatures was therefore examined. During oxidation gaseous selenium dioxide was formed and could be separated from the other elements, which remained in solid state. Upon cooling, the selenium dioxide sublimes and can be collected as crystals. After oxidation for 1 h at 800 °C all of the selenium was separated from the CIGS material. Two different reduction methods for reduction of the selenium dioxide to selenium were tested. In the first reduction method an organic molecule was used as the reducing agent in a Riley reaction. In the second reduction method sulphur dioxide gas was used. Both methods resulted in high purity selenium. This proves that the studied selenium separation method could be the first step in a recycling process aimed at the complete separation and recovery of high purity elements from CIGS.« less

Selenium requirement of shrimp Penaeus chinensis

NASA Astrophysics Data System (ADS)

Tian, Yuchuan; Liu, Fayi

1993-09-01

Penaeus chinensis were reared in fibreglass tanks for the study of their selenium requirements. The shrimp were fed semipurified diets containing graded levels of selenium, and weight gains, activities of glutatione peroxidase (GSH-Px) and selenium contents in muscle and hepatopancreas were determined. Weight gain and GSH-Px activity were the highest when the shrimp were fed diet containing 20 mg/kg selenium. Good linear correlation was found between GSH-Px activities and selenium contents in the diets, and the number of healthy shrimp. The experiment showed that 20 mg/kg selenium in the diet is optimal for the shrimp and that GSH-Px activity can be an important biochemical index of the selenium nutrition status of the animal.

Geologic sources and concentrations of selenium in the West-Central Denver Basin, including the Toll Gate Creek watershed, Aurora, Colorado, 2003-2007

USGS Publications Warehouse

Paschke, Suzanne S.; Walton-Day, Katherine; Beck, Jennifer A.; Webbers, Ank; Dupree, Jean A.

2014-01-01

Toll Gate Creek, in the west-central part of the Denver Basin, is a perennial stream in which concentrations of dissolved selenium have consistently exceeded the Colorado aquatic-life standard of 4.6 micrograms per liter. Recent studies of selenium in Toll Gate Creek identified the Denver lignite zone of the non-marine Cretaceous to Tertiary-aged (Paleocene) Denver Formation underlying the watershed as the geologic source of dissolved selenium to shallow ground-water and surface water. Previous work led to this study by the U.S. Geological Survey, in cooperation with the City of Aurora Utilities Department, which investigated geologic sources of selenium and selenium concentrations in the watershed. This report documents the occurrence of selenium-bearing rocks and groundwater within the Cretaceous- to Tertiary-aged Denver Formation in the west-central part of the Denver Basin, including the Toll Gate Creek watershed. The report presents background information on geochemical processes controlling selenium concentrations in the aquatic environment and possible geologic sources of selenium; the hydrogeologic setting of the watershed; selenium results from groundwater-sampling programs; and chemical analyses of solids samples as evidence that weathering of the Denver Formation is a geologic source of selenium to groundwater and surface water in the west-central part of the Denver Basin, including Toll Gate Creek. Analyses of water samples collected from 61 water-table wells in 2003 and from 19 water-table wells in 2007 indicate dissolved selenium concentrations in groundwater in the west-central Denver Basin frequently exceeded the Colorado aquatic-life standard and in some locations exceeded the primary drinking-water standard of 50 micrograms per liter. The greatest selenium concentrations were associated with oxidized groundwater samples from wells completed in bedrock materials. Selenium analysis of geologic core samples indicates that total selenium concentrations were greatest in samples containing indications of reducing conditions and organic matter (dark gray to black claystones and lignite horizons). The Toll Gate Creek watershed is situated in a unique hydrogeologic setting in the west-central part of the Denver Basin such that weathering of Cretaceous- to Tertiary-aged, non-marine, selenium-bearing rocks releases selenium to groundwater and surface water under present-day semi-arid environmental conditions. The Denver Formation contains several known and suspected geologic sources of selenium including: (1) lignite deposits; (2) tonstein partings; (3) organic-rich bentonite claystones; (4) salts formed as secondary weathering products; and possibly (5) the Cretaceous-Tertiary boundary. Organically complexed selenium and/or selenium-bearing pyrite in the enclosing claystones are likely the primary mineral sources of selenium in the Denver Formation, and correlations between concentration of dissolved selenium and dissolved organic carbon in groundwater indicate weathering and dissolution of organically complexed selenium from organic-rich claystone is a primary process mobilizing selenium. Secondary salts accumulated along fractures and bedding planes in the weathered zone are another potential geologic source of selenium, although their composition was not specifically addressed by the solids analyses. Results from this and previous work indicate that shallow groundwater and streams similarly positioned over Denver Formation claystone units at other locations in the Denver Basin also may contain concentrations of dissolved selenium greater than the Colorado aquatic-life standard or the drinking- water standard.

Thioredoxin binding protein (TBP)-2/Txnip and α-arrestin proteins in cancer and diabetes mellitus

PubMed Central

Masutani, Hiroshi; Yoshihara, Eiji; Masaki, So; Chen, Zhe; Yodoi, Junji

2012-01-01

Thioredoxin binding protein −2/ thioredoxin interacting protein is an α-arrestin protein that has attracted much attention as a multifunctional regulator. Thioredoxin binding protein −2 expression is downregulated in tumor cells and the level of thioredoxin binding protein is correlated with clinical stage of cancer. Mice with mutations or knockout of the thioredoxin binding protein −2 gene are much more susceptible to carcinogenesis than wild-type mice, indicating a role for thioredoxin binding protein −2 in cancer suppression. Studies have also revealed roles for thioredoxin binding protein −2 in metabolic control. Enhancement of thioredoxin binding protein −2 expression causes impairment of insulin sensitivity and glucose-induced insulin secretion, and β-cell apoptosis. These changes are important characteristics of type 2 diabetes mellitus. Thioredoxin binding protein −2 regulates transcription of metabolic regulating genes. Thioredoxin binding protein −2-like inducible membrane protein/ arrestin domain containing 3 regulates endocytosis of receptors such as the β2-adrenergic receptor. The α-arrestin family possesses PPXY motifs and may function as an adaptor/scaffold for NEDD family ubiquitin ligases. Elucidation of the molecular mechanisms of α-arrestin proteins would provide a new pharmacological basis for developing approaches against cancer and type 2 diabetes mellitus. PMID:22247597

Insights for Setting of Nutrient Requirements, Gleaned by Comparison of Selenium Status Biomarkers in Turkeys and Chickens versus Rats, Mice, and Lambs12

PubMed Central

Sunde, Roger A; Li, Jin-Long; Taylor, Rachel M

2016-01-01

To gain insights into nutrient biomarkers and setting of dietary nutrient requirements, selenium biomarker levels and requirements in response to multiple graded levels of dietary selenium were compared between day-old turkeys and chickens versus weanling rats and mice and 2-d-old lambs supplemented with sodium selenite. In rodents, there was no significant effect of dietary selenium on growth, indicating that the minimum selenium requirement was <0.007 μg Se/g diet. In contrast, there was a significant effect in turkeys, chicks, and lambs, which showed selenium requirements for growth of 0.05, 0.025, and 0.05 μg Se/g diet, respectively. Liver glutathione peroxidase (GPX) 1 activity fell in all species to <4% of selenium-adequate levels, plasma GPX3 activity fell to <3% in all species except for mice, and liver GPX4 activity fell to <10% in avians but only to ∼50% of selenium-adequate levels in rodents. Selenium-response curves for these biomarkers reached well-defined plateaus with increasing selenium supplementation in all species, collectively indicating minimum selenium requirements of 0.06–0.10 μg Se/g for rats, mice, and lambs but 0.10–0.13 μg Se/g for chicks and 0.23–0.33 μg Se/g for turkeys. In contrast, increasing dietary selenium did not result in well-defined plateaus for erythrocyte GPX1 activity and liver selenium in most species. Selenium-response curves for GPX1 mRNA for rodents and avians had well-defined plateaus and similar breakpoints. GPX4 mRNA was not significantly regulated by dietary selenium in rodents, but GPX4 mRNA in avians decreased in selenium deficiency to ∼35% of selenium-adequate plateau levels. Notably, no selenoprotein activities or mRNA were effective biomarkers for supernutritional selenium status. Robust biomarkers, such as liver GPX1 and plasma GPX3 activity for selenium, should be specific for the nutrient, fall dramatically in deficiency, and reach well-defined plateaus. Differences in biomarker-response curves may help researchers better understand nutrient metabolism and targeting of tissues in deficiency, thus to better characterize requirements. PMID:28140330

Insights for Setting of Nutrient Requirements, Gleaned by Comparison of Selenium Status Biomarkers in Turkeys and Chickens versus Rats, Mice, and Lambs.

PubMed

Sunde, Roger A; Li, Jin-Long; Taylor, Rachel M

2016-11-01

To gain insights into nutrient biomarkers and setting of dietary nutrient requirements, selenium biomarker levels and requirements in response to multiple graded levels of dietary selenium were compared between day-old turkeys and chickens versus weanling rats and mice and 2-d-old lambs supplemented with sodium selenite. In rodents, there was no significant effect of dietary selenium on growth, indicating that the minimum selenium requirement was <0.007 μg Se/g diet. In contrast, there was a significant effect in turkeys, chicks, and lambs, which showed selenium requirements for growth of 0.05, 0.025, and 0.05 μg Se/g diet, respectively. Liver glutathione peroxidase (GPX) 1 activity fell in all species to <4% of selenium-adequate levels, plasma GPX3 activity fell to <3% in all species except for mice, and liver GPX4 activity fell to <10% in avians but only to ∼50% of selenium-adequate levels in rodents. Selenium-response curves for these biomarkers reached well-defined plateaus with increasing selenium supplementation in all species, collectively indicating minimum selenium requirements of 0.06-0.10 μg Se/g for rats, mice, and lambs but 0.10-0.13 μg Se/g for chicks and 0.23-0.33 μg Se/g for turkeys. In contrast, increasing dietary selenium did not result in well-defined plateaus for erythrocyte GPX1 activity and liver selenium in most species. Selenium-response curves for GPX1 mRNA for rodents and avians had well-defined plateaus and similar breakpoints. GPX4 mRNA was not significantly regulated by dietary selenium in rodents, but GPX4 mRNA in avians decreased in selenium deficiency to ∼35% of selenium-adequate plateau levels. Notably, no selenoprotein activities or mRNA were effective biomarkers for supernutritional selenium status. Robust biomarkers, such as liver GPX1 and plasma GPX3 activity for selenium, should be specific for the nutrient, fall dramatically in deficiency, and reach well-defined plateaus. Differences in biomarker-response curves may help researchers better understand nutrient metabolism and targeting of tissues in deficiency, thus to better characterize requirements. © 2016 American Society for Nutrition.

Discovery of binding proteins for a protein target using protein-protein docking-based virtual screening.

PubMed

Zhang, Changsheng; Tang, Bo; Wang, Qian; Lai, Luhua

2014-10-01

Target structure-based virtual screening, which employs protein-small molecule docking to identify potential ligands, has been widely used in small-molecule drug discovery. In the present study, we used a protein-protein docking program to identify proteins that bind to a specific target protein. In the testing phase, an all-to-all protein-protein docking run on a large dataset was performed. The three-dimensional rigid docking program SDOCK was used to examine protein-protein docking on all protein pairs in the dataset. Both the binding affinity and features of the binding energy landscape were considered in the scoring function in order to distinguish positive binding pairs from negative binding pairs. Thus, the lowest docking score, the average Z-score, and convergency of the low-score solutions were incorporated in the analysis. The hybrid scoring function was optimized in the all-to-all docking test. The docking method and the hybrid scoring function were then used to screen for proteins that bind to tumor necrosis factor-α (TNFα), which is a well-known therapeutic target for rheumatoid arthritis and other autoimmune diseases. A protein library containing 677 proteins was used for the screen. Proteins with scores among the top 20% were further examined. Sixteen proteins from the top-ranking 67 proteins were selected for experimental study. Two of these proteins showed significant binding to TNFα in an in vitro binding study. The results of the present study demonstrate the power and potential application of protein-protein docking for the discovery of novel binding proteins for specific protein targets. © 2014 Wiley Periodicals, Inc.

Chemical Form of Selenium in Naturally Selenium-Rich Lentils (Lens Culinaris L.) From Saskatchewan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thavarajah, D.; Vandenberg, A.; George, G.N.

2009-06-04

Lentils (Lens culinaris L.) are a source of many essential dietary components and trace elements for human health. In this study we show that lentils grown in the Canadian prairies are additionally enriched in selenium, an essential micronutrient needed for general well-being, including a healthy immune system and protection against cancer. Selenium K near-edge X-ray absorption spectroscopy (XAS) has been used to examine the selenium biochemistry of two lentil cultivars grown in various locations in Saskatchewan, Canada. We observe significant variations in total selenium concentration with geographic location and cultivar; however, almost all the selenium (86--95%) in these field-grown lentilsmore » is present as organic selenium modeled as selenomethionine with a small component (5--14%) as selenate. As the toxicities of certain forms of arsenic and selenium are antagonistic, selenium-rich lentils may have a pivotal role to play in alleviating the chronic arsenic poisoning in Bangladesh.« less

The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease.

PubMed

R Cardoso, Bárbara; Hare, Dominic J; Lind, Monica; McLean, Catriona A; Volitakis, Irene; Laws, Simon M; Masters, Colin L; Bush, Ashley I; Roberts, Blaine R

2017-07-19

The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer's disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer's disease and control brain tissue. We found that Alzheimer's disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.

Both Selenium Deficiency and Modest Selenium Supplementation Lead to Myocardial Fibrosis in Mice via Effects on Redox-Methylation Balance

PubMed Central

Metes-Kosik, Nicole; Luptak, Ivan; DiBello, Patricia M.; Handy, Diane E.; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W.; Loscalzo, Joseph; Joseph, Jacob

2013-01-01

Scope Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. Methods and Results We examined the effects of selenium deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Conclusions Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. PMID:23097236

Toxicity of seleno-l-methionine, seleno-dl-methionine, high selenium wheat, and selenized yeast to mallard ducklings

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.; LeCaptain, L.J.

1996-01-01

The toxicity of four chemical forms of selenium (seleno-L-methionine, seleno-DL-methionine, selenized yeast, and high selenium wheat) was compared in day-old mallard ducklings (Anas platyrhynchos). In the first experiment, in which the basal diet was 75% wheat, survival after 2 weeks was lower for ducklings fed 30 ?g/g selenium as seleno-L-methionine (36%) than for ducklings fed 30 ?g/g selenium as seleno-DL-methionine (100%) or 30 ?g/g selenium from high selenium yeast (88%). In a second experiment, in which the basal diet was a commercial duck feed, survival after 2 weeks was 100% in ducklings fed 30 ?g/g selenium as seleno-DL-methionine, seleno-L-methionine, or selenized yeast. The greater toxicity of the L form of selenomethionine was probably related to the palatability or nutritional nature of the wheat-based diet used in experiment 1, but the exact reason for the difference between the DL and L forms is unknown. Biologically incorporated selenium, derived from high selenium wheat was no more toxic than selenium derived from the two purified forms of selenomethionine, and the selenium in selenized yeast was not as toxic as that in the two forms of selenomethionine.

Health risk assessment of environmental selenium: Emerging evidence and challenges

PubMed Central

Vinceti, Marco; Filippini, Tommaso; Cilloni, Silvia; Bargellini, Annalisa; Vergoni, Anna Valeria; Tsatsakis, Aristides; Ferrante, Margherita

2017-01-01

New data have been accumulated in the scientific literature in recent years which allow a more adequate risk assessment of selenium with reference to human health. This new evidence comes from environmental studies, carried out in populations characterized by abnormally high or low selenium intakes, and from high-quality and large randomized controlled trials with selenium recently carried out in the US and in other countries. These trials have consistently shown no beneficial effect on cancer and cardiovascular risk, and have yielded indications of unexpected toxic effects of selenium exposure. Overall, these studies indicate that the minimal amount of environmental selenium which is source of risk to human health is much lower than anticipated on the basis of older studies, since toxic effects were shown at levels of intake as low as around 260 µg/day for organic selenium and around 16 µg/day for inorganic selenium. Conversely, populations with average selenium intake of less than 13–19 µg/day appear to be at risk of a severe cardiomyopathy, Keshan disease. Overall, there is the need to reconsider the selenium standards for dietary intake, drinking water, outdoor and indoor air levels, taking into account the recently discovered adverse health effects of low-dose selenium overexposure, and carefully assessing the significance of selenium-induced proteomic changes. PMID:28339083

Production and Release of Selenomethionine and Related Organic Selenium Species by Microorganisms in Natural and Industrial Waters.

PubMed

LeBlanc, Kelly L; Wallschläger, Dirk

2016-06-21

Laboratory algal cultures exposed to selenate were shown to produce and release selenomethionine, selenomethionine oxide, and several other organic selenium metabolites. Released discrete organic selenium species accounted for 1.6-13.1% of the selenium remaining in the media after culture death, with 1.3-6.1% of the added selenate recovered as organic metabolites. Analysis of water from an industrially impacted river collected immediately after the death of massive annual algal blooms showed that no selenomethionine or selenomethionine oxide was present. However, other discrete organic selenium species, including a cyclic oxidation product of selenomethionine, were observed, indicating the previous presence of selenomethionine. Industrial biological treatment systems designed for remediation of selenium-contaminated waters were shown to increase both the concentration of organic selenium species in the effluent, relative to influent water, and the fraction of organic selenium to up to 8.7% of the total selenium in the effluent, from less than 1.1% in the influent. Production and emission of selenomethionine, selenomethionine oxide, and other discrete organic selenium species were observed. These findings are discussed in the context of potentially increased selenium bioavailability caused by microbial activity in aquatic environments and biological treatment systems, despite overall reductions in total selenium concentration.

Health risk assessment of environmental selenium: Emerging evidence and challenges (Review).

PubMed

Vinceti, Marco; Filippini, Tommaso; Cilloni, Silvia; Bargellini, Annalisa; Vergoni, Anna Valeria; Tsatsakis, Aristides; Ferrante, Margherita

2017-05-01

New data have been accumulated in the scientific literature in recent years which allow a more adequate risk assessment of selenium with reference to human health. This new evidence comes from environmental studies, carried out in populations characterized by abnormally high or low selenium intakes, and from high-quality and large randomized controlled trials with selenium recently carried out in the US and in other countries. These trials have consistently shown no beneficial effect on cancer and cardiovascular risk, and have yielded indications of unexpected toxic effects of selenium exposure. Overall, these studies indicate that the minimal amount of environmental selenium which is source of risk to human health is much lower than anticipated on the basis of older studies, since toxic effects were shown at levels of intake as low as around 260 µg/day for organic selenium and around 16 µg/day for inorganic selenium. Conversely, populations with average selenium intake of less than 13-19 µg/day appear to be at risk of a severe cardiomyopathy, Keshan disease. Overall, there is the need to reconsider the selenium standards for dietary intake, drinking water, outdoor and indoor air levels, taking into account the recently discovered adverse health effects of low-dose selenium overexposure, and carefully assessing the significance of selenium-induced proteomic changes.

Features of selenium metabolism in humans living under the conditions of North European Russia.

PubMed

Parshukova, Olga; Potolitsyna, Natalya; Shadrina, Vera; Chernykh, Aleksei; Bojko, Evgeny

2014-08-01

Selenium supplementation and its effects on Northerners have been little studied. The aim of our study was to assess the selenium levels of the inhabitants of North European Russia, the seasonal aspects of selenium supplementation, and the interrelationships between selenium levels and the levels of thyroid gland hormones. To study the particular features of selenium metabolism in Northerners over the course of 1 year, 19 healthy male Caucasian volunteers (18-21 years old) were recruited for the present study. The subjects were military guards in a Northern European region of Russia (Syktyvkar, Russia, 62°N latitude) who spent 6-10-h outdoors daily. The study was conducted over a 12-month period. Selenium levels, glutathione peroxidase (GP) activity, as well as total triiodothyronine (T3), total thyroxin (T4), free thyroxin, free triiodothyronine, and thyrotropin (TSH) levels, were determined in the blood serum. The study subjects showed low levels of plasma selenium throughout the year. We observed a noticeable decrease in plasma selenium levels during the period from May to August, with the lowest levels in July. Selenium levels in the military guards correlated with the levels of selenium-dependent GP enzyme activity throughout the year. Additionally, we demonstrated a significant correlation between selenium and pituitary-thyroid axis hormones (total T3, free T4, and TSH) in periods in which plasma selenium levels were lower than the established normal ranges. Over the course of 1 year, low levels of plasma selenium affect GP activity and thyroid hormone levels in humans living in North European Russia.

Functional assignment of solute-binding proteins of ABC transporters using a fluorescence-based thermal shift assay.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giulliani, S. E.; Frank, A. E.; Collart, F. R.

2008-12-08

We have used a fluorescence-based thermal shift (FTS) assay to identify amino acids that bind to solute-binding proteins in the bacterial ABC transporter family. The assay was validated with a set of six proteins with known binding specificity and was consistently able to map proteins with their known binding ligands. The assay also identified additional candidate binding ligands for several of the amino acid-binding proteins in the validation set. We extended this approach to additional targets and demonstrated the ability of the FTS assay to unambiguously identify preferential binding for several homologues of amino acid-binding proteins with known specificity andmore » to functionally annotate proteins of unknown binding specificity. The assay is implemented in a microwell plate format and provides a rapid approach to validate an anticipated function or to screen proteins of unknown function. The ABC-type transporter family is ubiquitous and transports a variety of biological compounds, but the current annotation of the ligand-binding proteins is limited to mostly generic descriptions of function. The results illustrate the feasibility of the FTS assay to improve the functional annotation of binding proteins associated with ABC-type transporters and suggest this approach that can also be extended to other protein families.« less

[Effect of fluorine, selenium and cadmium on anti-oxidase and microelements in rat's body].

PubMed

Mou, Suhua; Qin, Si; Hu, Qituo; Duan, Xianyu

2004-03-01

To study the effect of fluorine, selenium and cadmium on lipid peroxide(LPO), the activity of glutathione peroxidase (GSH-Px) and microelements such as cadmium, selenium and zinc in rats. Measurement of the contents of LPO, GSH-Px and microelements such as cadmium, selenium and zinc in SD rats after killing that have drunk water containing fluorine, selenium and cadmium eight-week ago. The contents of GSH-Px in the serum, liver and kidney of rats that were contaminated with fluorine, selenium and cadmium respectively remarkably reduced and the content of LPO noticeably increased in comparison with those of rats without being contaminated. The contents of GSH-Px noticeably increased and LPO remarkably reduced in those contaminated with the combination of any two of the three elements when compared with those in the rats contaminated with any one element of them, while the contents of GSH-Px in those contaminated with the combination of the three elements increased even more. Excessive selenium or cadmium led to the increase of selenium content in kidney and cadmium content in liver by several times. Excessive fluorine or cadmium gave rise to the lack of selenium and zinc. Selenium brought out universal increase of zinc in liver and kidney. The combination of fluorine and selenium or the combination of cadmium and selenium or that of fluorine, selenium and cadmium produced remarkable decrease of the accumulation of selenium in kidney and cadmium in liver. They also lowed the loss of zinc caused by fluorine or cadmium. Excessive fluorine, selenium or cadmium could inhabit the activity of GSH-Px in rats, which could diminish the antioxidation ability of the body. But when two or three of the chemical elements coexisted, they reduced the inhabitation of each of them on the activity of GSH-Px and in the meantime decreased the accumulation of cadmium and selenium and diminished the loss of zinc caused by fluorine and cadmium.

An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Republican River Basin: 1997-1999.

PubMed

May, T W; Walther, M J; Petty, J D; Fairchild, J F; Lucero, J; Delvaux, M; Manring, J; Armbruster, M; Hartman, D

2001-11-01

The Republican River Basin of Colorado, Nebraska, and Kansas lies in a valley which contains Pierre Shale as part of its geological substrata. Selenium is an indigenous constituent in the shale and is readily leached into surrounding groundwater. The Basin is heavily irrigated through the pumping of groundwater, some of which is selenium-contaminated, onto fields in agricultural production. Water, sediment, benthic invertebrates, and/or fish were collected from 46 sites in the Basin and were analyzed for selenium to determine the potential for food-chain bioaccumulation, dietary toxicity, and reproductive effects of selenium in biota. Resulting selenium concentrations were compared to published guidelines or biological effects thresholds. Water from 38% of the sites (n = 18) contained selenium concentrations exceeding 5 microg L(-1), which is reported to be a high hazard for selenium accumulation into the planktonic food chain. An additional 12 sites (26% of the sites) contained selenium in water between 3-5 microg L(-1), constituting a moderate hazard. Selenium concentrations in sediment indicated little to no hazard for selenium accumulation from sediments into the benthic food chain. Ninety-five percent of benthic invertebrates collected exhibited selenium concentrations exceeding 3 microg g(-1), a level reported as potentially lethal to fish and birds that consume them. Seventy-five percent of fish collected in 1997, 90% in 1998, and 64% in 1999 exceeded 4 microg g(-1) selenium, indicating a high potential for toxicity and reproductive effects. However, examination of weight profiles of various species of collected individual fish suggested successful recruitment in spite of selenium concentrations that exceeded published biological effects thresholds for health and reproductive success. This finding suggested that universal application of published guidelines for selenium may be inappropriate or at least may need refinement for systems similar to the Republican River Basin. Additional research is needed to determine the true impact of selenium on fish and wildlife resources in the Basin.

Biological changes of green pea (Pisum sativum L.) by selenium enrichment.

PubMed

Garousi, Farzaneh; Kovács, Béla; Domokos-Szabolcsy, Éva; Veres, Szilvia

2017-03-01

Supplement of common fertilizers with selenium (Se) for crop production will be an effective way to produce selenium-rich food and feed. The value of green pea seeds and forages as alternative protein source can be improved by using agronomic biofortification. Therefore, biological changes of green pea (Pisum sativum L.) and influences of inorganic forms of Se (sodium selenite and sodium selenate) at different concentrations on the accumulation of magnesium (Mg) and phosphorus (P) were investigated in greenhouse experiment. 3 mg kg -1 of selenite had positive effects to enhance photosynthetic attributes and decrease lipid peroxidation significantly. At the same time, Se accumulation increased in all parts of plant by increasing Se supply. Moreover, Mg and P accumulations were significantly increased at 3 mg kg -1 selenite and 1 mg kg -1 selenate treatments, respectively. By contrast higher selenite concentrations (≥30 mg kg -1 ) exerted toxic effects on plants. Relative chlorophyll content, actual photochemical efficiency of PSII (Ф PSII ) and Mg accumulation showed significant decrease while membrane lipid peroxidation increased. Thus, the present findings prove Se biofortification has positive effects on biological traits of green pea to provide it as a proper functional product.

Food proteins and maturation of small intestinal microvillus membranes (MVM). I. Binding characteristics of cow's milk proteins and concanavalin A to MVM from newborn and adult rats.

PubMed

Stern, M; Gellermann, B

1988-01-01

To study maturational changes of food protein and lectin binding to rat small intestinal microvillus membranes (MVM), MVM were prepared from newborn and adult animals by a modified CaCl2 precipitation technique. Radiolabeled cow's milk proteins [alpha-lactalbumin, alpha-casein, beta-lactoglobulin, bovine serum albumin (BSA)] and the lectin concanavalin A (Con A) were used for incubations. Binding assays were done using miniature ultracentrifugation for separation of unbound material. Binding of Con A to MVM from newborn and adult rats was strong, specific, and saturable. Binding of Con A was inhibited by cold Con A and by the sugar ligand polymer mannan. Adult MVM bound more Con A than newborn preparations. Unlike Con A, binding of cow's milk proteins by MVM was weak, nonspecific, and noninhibitable. Newborn MVM bound more cow's milk proteins than adult controls. This was true for all the proteins tested (p less than 0.001). Binding rose with decreased molecular weight of cow's milk proteins, but molecular weight was not the only determining factor for binding. Trypsin treatment of MVM caused a marked increase of BSA binding in adult but not in newborn preparations. This finding indicated the importance of protein components of MVM for cow's milk protein binding. Maturational changes in protein-lipid interactions and membrane fluidity possibly influence nonspecific cow's milk protein binding to MVM. Differences in binding between newborns and adults were not directly related to maturational shifts in membrane glycosylation that are indicated by differential Con A binding. Increased cow's milk protein binding in newborn individuals might increase the potential risk to develop an adverse reaction to food proteins.

Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor.

PubMed

Miao, Yinglong; McCammon, J Andrew

2018-03-20

Protein-protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein-protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. Here, we report a successful simulation of the binding of a G-protein mimetic nanobody to the M 2 muscarinic GPCR using the robust Gaussian accelerated MD (GaMD) method. Through long-timescale GaMD simulations over 4,500 ns, the nanobody was observed to bind the receptor intracellular G-protein-coupling site, with a minimum rmsd of 2.48 Å in the nanobody core domain compared with the X-ray structure. Binding of the nanobody allosterically closed the orthosteric ligand-binding pocket, being consistent with the recent experimental finding. In the absence of nanobody binding, the receptor orthosteric pocket sampled open and fully open conformations. The GaMD simulations revealed two low-energy intermediate states during nanobody binding to the M 2 receptor. The flexible receptor intracellular loops contribute remarkable electrostatic, polar, and hydrophobic residue interactions in recognition and binding of the nanobody. These simulations provided important insights into the mechanism of GPCR-nanobody binding and demonstrated the applicability of GaMD in modeling dynamic protein-protein interactions.

Selenium nanoparticles: potential in cancer gene and drug delivery.

PubMed

Maiyo, Fiona; Singh, Moganavelli

2017-05-01

In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

Variations in the accumulation, localization and rate of metabolization of selenium in mature Zea mays plants supplied with selenite or selenate.

PubMed

Longchamp, Mélanie; Castrec-Rouelle, Maryse; Biron, Philippe; Bariac, Thierry

2015-09-01

Quantification of selenium bioavailability from foods is a key challenge following the discovery of the antioxidant role of this micronutrient in human health. This study presents the uptake, accumulation and rate of metabolization in mature Zea mays plants grown in hydroponic solution supplemented with selenate or selenite. Selenium content was lower in plants supplemented with selenate and accumulated mainly in the leaves compared with selenite-treated plants where the selenium was retained in the roots. Selenite-treated grains accumulated more selenium. Selenate was metabolized less than selenite in whole plants, but in grains selenium was present exclusively as organic selenium compounds. For humans, the bioavailability of organic selenium was evaluated at 90% compared with only 50% for inorganic forms. Our results show that the potential for selenium bioavailability is increased with selenite treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

The facts and controversies about selenium.

PubMed

Dodig, Slavica; Cepelak, Ivana

2004-12-01

Selenium is a trace element, essential in small amounts, but it can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal functioning of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. Selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation plays a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.

High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malinouski, M.; Kehr, S.; Finney, L.

2012-04-17

Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts ofmore » the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.« less

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA.

PubMed

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2013-01-15

A number of contaminants affect fish health, including mercury and selenium, and the selenium:mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) (n=40) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium:mercury molar ratios by tissues. Total mercury averaged 0.32±0.02 ppm wet weight in edible muscle and 0.09±0.01 ppm in brain. Selenium concentration averaged 0.37±0.03 in muscle and 0.36±0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium:mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium:mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. Copyright © 2012 Elsevier B.V. All rights reserved.

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study.

PubMed

Flax, Valerie L; Bentley, Margaret E; Combs, Gerald F; Chasela, Charles S; Kayira, Dumbani; Tegha, Gerald; Kamwendo, Debbie; Daza, Eric J; Fokar, Ali; Kourtis, Athena P; Jamieson, Denise J; van der Horst, Charles M; Adair, Linda S

2014-04-01

Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.

Deficient selenium status of a healthy adult Spanish population.

PubMed

Millán Adame, E; Florea, D; Sáez Pérez, L; Molina López, J; López-González, B; Pérez de la Cruz, A; Planells del Pozo, E

2012-01-01

Selenium is an essential micronutrient for human health, being a cofactor for enzymes with antioxidant activity that protect the organism from oxidative damage. An inadequate intake of this mineral has been associated with the onset and progression of chronic diseases such as hypertension, diabetes, coronary diseases, asthma, and cancer. For this reason, knowledge of the plasma and erythrocyte selenium levels of a population makes a relevant contribution to assessment of its nutritional status. The objective of the present study was to determine the nutritional status of selenium and risk of selenium deficiency in a healthy adult population in Spain by examining food and nutrient intake and analyzing biochemical parameters related to selenium metabolism, including plasma and erythrocyte levels and selenium-dependent glutathione peroxidase (GPx) enzymatic activity. We studied 84 healthy adults (31 males and 53 females) from the province of Granada, determining their plasma and erythrocyte selenium concentrations and the association of these levels with the enzymatic activity of glutathione peroxidase (GPx) and with life style factors. We also gathered data on their food and nutrient intake and the results of biochemical analyses. Correlations were studied among all of these variables. The mean plasma selenium concentration was 76.6 ± 17.3 μg/L (87.3 ± 17.4 μg/L in males, 67.3 ± 10.7 μg/L in females), whereas the mean erythrocyte selenium concentration was 104.6 μg/L (107.9 ± 26.1 μg/L in males and 101.7 ± 21.7 μg/L in females). The nutritional status of selenium was defined by the plasma concentration required to reach maximum GPx activity, establishing 90 μg/L as reference value. According to this criterion, 50% of the men and 53% of the women were selenium deficient. Selenium is subjected to multiple regulation mechanisms. Erythrocyte selenium is a good marker of longer term selenium status, while plasma selenium appears to be a marker of short-term nutritional status. The present findings indicate a positive correlation between plasma selenium concentration and the practice of physical activity. Bioavailability studies are required to establish appropriate reference levels of this mineral for the Spanish population.

Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia.

PubMed

Mohammadi, Alireza; Rashidi, Ehsan; Amooeian, Vahid Ghasem

2018-04-13

Over the last decade, finding a reliable biomarker for the early detection of schizophrenia (Scz) has been a topic of interest. The main goal of the current review is to provide a comprehensive view of the brain, blood, cerebrospinal fluid (CSF), and serum biomarkers of Scz disease. Imaging studies have demonstrated that the volumes of the corpus callosum, thalamus, hippocampal formation, subiculum, parahippocampal gyrus, superior temporal gyrus, prefrontal and orbitofrontal cortices, and amygdala-hippocampal complex were reduced in patients diagnosed with Scz. It has been revealed that the levels of interleukin 1β (IL-1β), IL-6, IL-8, and TNF-α were increased in patients with Scz. Decreased mRNA levels of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), neurotrophin-3 (NT-3), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) genes have also been reported in Scz patients. Genes with known strong relationships with this disease include BDNF, catechol-O-methyltransferase (COMT), regulator of G-protein signaling 4 (RGS4), dystrobrevin-binding protein 1 (DTNBP1), neuregulin 1 (NRG1), Reelin (RELN), Selenium-binding protein 1 (SELENBP1), glutamic acid decarboxylase 67 (GAD 67), and disrupted in schizophrenia 1 (DISC1). The levels of dopamine, tyrosine hydroxylase (TH), serotonin or 5-hydroxytryptamine (5-HT) receptor 1A and B (5-HTR1A and 5-HTR1B), and 5-HT1B were significantly increased in Scz patients, while the levels of gamma-aminobutyric acid (GABA), 5-HT transporter (5-HTT), and 5-HT receptor 2A (5-HTR2A) were decreased. The increased levels of SELENBP1 and Glycogen synthase kinase 3 subunit α (GSK3α) genes in contrast with reduced levels of B-cell translocation gene 1 (BTG1), human leukocyte antigen DRB1 (HLA-DRB1), heterogeneous nuclear ribonucleoprotein A3 (HNRPA3), and serine/arginine-rich splicing factor 1 (SFRS1) genes have also been reported. This review covers various dysregulation of neurotransmitters and also highlights the strengths and weaknesses of studies attempting to identify candidate biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

A tool for calculating binding-site residues on proteins from PDB structures.

PubMed

Hu, Jing; Yan, Changhui

2009-08-03

In the research on protein functional sites, researchers often need to identify binding-site residues on a protein. A commonly used strategy is to find a complex structure from the Protein Data Bank (PDB) that consists of the protein of interest and its interacting partner(s) and calculate binding-site residues based on the complex structure. However, since a protein may participate in multiple interactions, the binding-site residues calculated based on one complex structure usually do not reveal all binding sites on a protein. Thus, this requires researchers to find all PDB complexes that contain the protein of interest and combine the binding-site information gleaned from them. This process is very time-consuming. Especially, combing binding-site information obtained from different PDB structures requires tedious work to align protein sequences. The process becomes overwhelmingly difficult when researchers have a large set of proteins to analyze, which is usually the case in practice. In this study, we have developed a tool for calculating binding-site residues on proteins, TCBRP http://yanbioinformatics.cs.usu.edu:8080/ppbindingsubmit. For an input protein, TCBRP can quickly find all binding-site residues on the protein by automatically combining the information obtained from all PDB structures that consist of the protein of interest. Additionally, TCBRP presents the binding-site residues in different categories according to the interaction type. TCBRP also allows researchers to set the definition of binding-site residues. The developed tool is very useful for the research on protein binding site analysis and prediction.

Interaction entropy for protein-protein binding

NASA Astrophysics Data System (ADS)

Sun, Zhaoxi; Yan, Yu N.; Yang, Maoyou; Zhang, John Z. H.

2017-03-01

Protein-protein interactions are at the heart of signal transduction and are central to the function of protein machine in biology. The highly specific protein-protein binding is quantitatively characterized by the binding free energy whose accurate calculation from the first principle is a grand challenge in computational biology. In this paper, we show how the interaction entropy approach, which was recently proposed for protein-ligand binding free energy calculation, can be applied to computing the entropic contribution to the protein-protein binding free energy. Explicit theoretical derivation of the interaction entropy approach for protein-protein interaction system is given in detail from the basic definition. Extensive computational studies for a dozen realistic protein-protein interaction systems are carried out using the present approach and comparisons of the results for these protein-protein systems with those from the standard normal mode method are presented. Analysis of the present method for application in protein-protein binding as well as the limitation of the method in numerical computation is discussed. Our study and analysis of the results provided useful information for extracting correct entropic contribution in protein-protein binding from molecular dynamics simulations.

Interaction entropy for protein-protein binding.

PubMed

Sun, Zhaoxi; Yan, Yu N; Yang, Maoyou; Zhang, John Z H

2017-03-28

Protein-protein interactions are at the heart of signal transduction and are central to the function of protein machine in biology. The highly specific protein-protein binding is quantitatively characterized by the binding free energy whose accurate calculation from the first principle is a grand challenge in computational biology. In this paper, we show how the interactionentropy approach, which was recently proposed for protein-ligand binding free energy calculation, can be applied to computing the entropic contribution to the protein-protein binding free energy. Explicit theoretical derivation of the interactionentropy approach for protein-protein interaction system is given in detail from the basic definition. Extensive computational studies for a dozen realistic protein-protein interaction systems are carried out using the present approach and comparisons of the results for these protein-protein systems with those from the standard normal mode method are presented. Analysis of the present method for application in protein-protein binding as well as the limitation of the method in numerical computation is discussed. Our study and analysis of the results provided useful information for extracting correct entropic contribution in protein-protein binding from molecular dynamics simulations.

Electrode materials for rechargeable batteries

DOEpatents

Abouimrane, Ali; Amine, Khalil

2015-04-14

Selenium or selenium-containing compounds may be used as electroactive materials in electrodes or electrochemical devices. The selenium or selenium-containing compound is mixed with a carbon material.

Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells.

PubMed

Woods, Alison J; Roberts, Marnie S; Choudhary, Jyoti; Barry, Simon T; Mazaki, Yuichi; Sabe, Hisataka; Morley, Simon J; Critchley, David R; Norman, Jim C

2002-02-22

Using mass spectrometry we have identified proteins which co-immunoprecipitate with paxillin, an adaptor protein implicated in the integrin-mediated signaling pathways of cell motility. A major component of paxillin immunoprecipitates was poly(A)-binding protein 1, a 70-kDa mRNA-binding protein. Poly(A)-binding protein 1 associated with both the alpha and beta isoforms of paxillin, and this was unaffected by RNase treatment consistent with a protein-protein interaction. The NH(2)-terminal region of paxillin (residues 54-313) associated directly with poly(A)-binding protein 1 in cell lysates, and with His-poly(A)-binding protein 1 immobilized in microtiter wells. Binding was specific, saturable and of high affinity (K(d) of approximately 10 nm). Cell fractionation studies showed that at steady state, the bulk of paxillin and poly(A)-binding protein 1 was present in the "dense" polyribosome-associated endoplasmic reticulum. However, inhibition of nuclear export with leptomycin B caused paxillin and poly(A)-binding protein 1 to accumulate in the nucleus, indicating that they shuttle between the nuclear and cytoplasmic compartments. When cells migrate, poly(A)-binding protein 1 colocalized with paxillin-beta at the tips of lamellipodia. Our results suggest a new mechanism whereby a paxillin x poly(A)-binding protein 1 complex facilitates transport of mRNA from the nucleus to sites of protein synthesis at the endoplasmic reticulum and the leading lamella during cell migration.

Comparison of the Folding Mechanism of Highly Homologous Proteins in the Lipid-binding Protein Family

EPA Science Inventory

The folding mechanism of two closely related proteins in the intracellular lipid binding protein family, human bile acid binding protein (hBABP) and rat bile acid binding protein (rBABP) were examined. These proteins are 77% identical (93% similar) in sequence Both of these singl...

Effects of salts on protein-surface interactions: applications for column chromatography.

PubMed

Tsumoto, Kouhei; Ejima, Daisuke; Senczuk, Anna M; Kita, Yoshiko; Arakawa, Tsutomu

2007-07-01

Development of protein pharmaceuticals depends on the availability of high quality proteins. Various column chromatographies are used to purify proteins and characterize the purity and properties of the proteins. Most column chromatographies require salts, whether inorganic or organic, for binding, elution or simply better recovery and resolution. The salts modulate affinity of the proteins for particular columns and nonspecific protein-protein or protein-surface interactions, depending on the type and concentration of the salts, in both specific and nonspecific manners. Salts also affect the binding capacity of the column, which determines the size of the column to be used. Binding capacity, whether equilibrium or dynamic (under an approximation of a slow flow rate), depends on the binding constant, protein concentration and the number of the binding site on the column as well as nonspecific binding. This review attempts to summarize the mechanism of the salt effects on binding affinity and capacity for various column chromatographies and on nonspecific protein-protein or protein-surface interactions. Understanding such salt effects should also be useful in preventing nonspecific protein binding to various containers. Copyright 2007 Wiley-Liss, Inc.

Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study.

PubMed

Galan-Chilet, Inmaculada; Tellez-Plaza, Maria; Guallar, Eliseo; De Marco, Griselda; Lopez-Izquierdo, Raul; Gonzalez-Manzano, Isabel; Carmen Tormos, M; Martin-Nuñez, Gracia M; Rojo-Martinez, Gemma; Saez, Guillermo T; Martín-Escudero, Juan C; Redon, Josep; Javier Chaves, F

2014-09-01

The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Selenium and Selenoprotein Deficiencies Induce Widespread Pyogranuloma Formation in Mice, while High Levels of Dietary Selenium Decrease Liver Tumor Size Driven by TGFα

PubMed Central

Zhong, Nianxin; Ward, Jerrold M.; Perella, Christine M.; Hoffmann, Victoria J.; Rogers, Keith; Combs, Gerald F.; Schweizer, Ulrich; Merlino, Glenn; Gladyshev, Vadim N.; Hatfield, Dolph L.

2013-01-01

Changes in dietary selenium and selenoprotein status may influence both anti- and pro-cancer pathways, making the outcome of interventions different from one study to another. To characterize such outcomes in a defined setting, we undertook a controlled hepatocarcinogenesis study involving varying levels of dietary selenium and altered selenoprotein status using mice carrying a mutant (A37G) selenocysteine tRNA transgene (TrsptG37) and/or a cancer driver TGFα transgene. The use of TrsptG37 altered selenoprotein expression in a selenoprotein and tissue specific manner and, at sufficient dietary selenium levels, separate the effect of diet and selenoprotein status. Mice were maintained on diets deficient in selenium (0.02 ppm selenium) or supplemented with 0.1, 0.4 or 2.25 ppm selenium or 30 ppm triphenylselenonium chloride (TPSC), a non-metabolized selenium compound. TrsptG37 transgenic and TGFα/TrsptG37 bi-transgenic mice subjected to selenium-deficient or TPSC diets developed a neurological phenotype associated with early morbidity and mortality prior to hepatocarcinoma development. Pathology analyses revealed widespread disseminated pyogranulomatous inflammation. Pyogranulomas occurred in liver, lungs, heart, spleen, small and large intestine, and mesenteric lymph nodes in these transgenic and bi-transgenic mice. The incidence of liver tumors was significantly increased in mice carrying the TGFα transgene, while dietary selenium and selenoprotein status did not affect tumor number and multiplicity. However, adenoma and carcinoma size and area were smaller in TGFα transgenic mice that were fed 0.4 and 2.25 versus 0.1 ppm of selenium. Thus, selenium and selenoprotein deficiencies led to widespread pyogranuloma formation, while high selenium levels inhibited the size of TGFα–induced liver tumors. PMID:23460847

Impaired reproduction of mallards fed an organic form of selenium

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.; Gold, L.G.

1989-01-01

We fed mallards (Anas platyrhynchos) diets supplemented with 0-, 1-, 2-, 4-, 8-, or 16-ppm selenium in the form of selenomethionine. We fed another group of mallards a diet containing 16-ppm selenium as selenocystine. Females fed the control diet produced a mean of 8.1 ducklings that survived to 6 days of age, which was significantly greater than the 4.6 young produced by females fed 8-ppm selenium as selenomethionine and the zero surviving young of females fed 16-ppm selenium as selenomethionine. Selenocystine did not impair reproduction. Diets containing 8- and 16-ppm selenium as selenomethionine caused malformations in 6.8 and 67.9%, respectively, of unhatched eggs compared with 0.6% for controls. The most common malformations were of eyes, bill, legs, and feet. Selenium did not affect the onset or frequency of egg laying, egg size, shell thickness, fertility of eggs, or sex ratio of ducklings. Reduced survival and growth occurred in ducklings hatched from groups whose parents had received 8- or 16-ppm selenium as selenomethionine, even though all ducklings were fed a control diet. Concentrations of selenium in eggs and liver of adults could be predicted from dietary concentrations. We conclude that the dietary threshold of selenium as selenomethionine necessary to impair reproduction is between 4 and 8 ppm. It is difficult to identify 1 level of selenium in eggs that will be diagnostic of reproductive impairment in the field because different chemical forms of selenium appear to have different toxicities in eggs. However, when eggs from a wild population contain .gtoreq. 1-ppm selenium on a wet-weight basis, reproductive impairment may be possible and should be evaluated in that population. At 5-ppm selenium in eggs, reproductive impairment is much more likely to occur.

Impact of the Nationwide Intravenous Selenium Product Shortage on the Development of Selenium Deficiency in Infants Dependent on Long-Term Parenteral Nutrition.

PubMed

Chen, Connie H; Harris, Mary Beth; Partipilo, M Luisa; Welch, Kathleen B; Teitelbaum, Daniel H; Blackmer, Allison B

2016-08-01

For patients dependent on parenteral nutrition (PN), selenium must be supplemented intravenously. A nationwide intravenous selenium shortage began in April 2011. The impact of this shortage on PN-dependent infants was evaluated by examining the provision of selenium, development of biochemical deficiency, and costs associated with the shortage. This single-center, retrospective study included PN-dependent infants aged ≤1 year who weighed ≤30 kg, received PN for ≥1 month, and had ≥1 serum selenium measurement. The primary outcome was the incidence of biochemical selenium deficiency. Secondary outcomes included severity of biochemical deficiency, clinical manifestations, costs, and relationship between serum selenium levels and selenium dose. The average selenium dose decreased 2-fold during the shortage (2.1 ± 1.2 µg/kg/d; range, 0.2-4.6 µg/kg/d) versus the nonshortage period (3.8 ± 1 µg/kg/d; range, 2.4-6 µg/kg/d; P < .001). A linear relationship between serum selenium concentration and selenium dose was observed (r(2) = 0.42), with a dose of 6 µg/kg/d expected to result in normal serum levels in most cases. Similar proportions of patients developed biochemical deficiency in both groups: shortage period, 59.1%; nonshortage, 66.7%; P = .13. The severity of biochemical deficiency was similar between groups. A significant increase in incremental cost during the shortage was observed. This is the first study examining the impact of the intravenous selenium shortage on PN-dependent infants. Both groups exhibited similarly high incidences of biochemical selenium deficiency, suggesting higher empiric doses may benefit this population. However, ongoing shortages limit the ability to provide supplementation. © 2015 American Society for Parenteral and Enteral Nutrition.

Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.

PubMed

Metes-Kosik, Nicole; Luptak, Ivan; Dibello, Patricia M; Handy, Diane E; Tang, Shiow-Shih; Zhi, Hui; Qin, Fuzhong; Jacobsen, Donald W; Loscalzo, Joseph; Joseph, Jacob

2012-12-01

Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. We examined the effects of selenium-deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium-supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Speciation of selenium in stream insects using X-ray absorption spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruwandi Andrahennadi; Mark Wayland; Ingrid J. Pickering

2007-11-15

Selenium contamination in the environment is a widespread problem affecting insects and other wildlife. Insects occupy a critical middle link and aid in trophic transfer of selenium in many terrestrial and freshwater food chains, but the mechanisms of selenium uptake through the food chain are poorly understood. In particular, biotransformation of selenium by insects into different chemical forms will greatly influence how toxic or benign the selenium is to that organism or to its predators. We have used X-ray absorption spectroscopy (XAS) to identify the chemical form of selenium in insects inhabiting selenium contaminated streams near Hinton, Alberta (Canada). Seleniummore » K near-edge spectra indicate a variability of selenium speciation among the insects that included mayflies (Ephemeroptera), stoneflies (Plecoptera), caddisflies (Trichoptera), and craneflies (Diptera). Higher percentages of inorganic selenium were observed in primary consumers, detritivores, and filter feeders than in predatory insects. Among the organic forms of selenium, organic selenides constituted a major fraction in most organisms. A species modeled as trimethylselenonium was observed during the pupal stage of caddisflies. These results provide insights into how the insects cope with their toxic cargo, including how the selenium is biotransformed into less toxic forms and how it can be eliminated from the insects. More broadly, this study demonstrates the strengths of XAS to probe the effects of heavy elements at trace levels in insects from the field.« less

Speciation of Selenium in Stream Insects Using X-Ray Absorption Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrahennadi, R.; Wayland, M.; Pickering, I.J.

2009-05-28

Selenium contamination in the environment is a widespread problem affecting insects and other wildlife. Insects occupy a critical middle link and aid in trophic transfer of selenium in many terrestrial and freshwater food chains, but the mechanisms of selenium uptake through the food chain are poorly understood. In particular, biotransformation of selenium by insects into different chemical forms will greatly influence how toxic or benign the selenium is to that organism or to its predators. We have used X-ray absorption spectroscopy (XAS) to identify the chemical form of selenium in insects inhabiting selenium contaminated streams near Hinton, Alberta (Canada). Seleniummore » K near-edge spectra indicate a variability of selenium speciation among the insects that included mayflies (Ephemeroptera), stoneflies (Plecoptera), caddisflies (Trichoptera), and craneflies (Diptera). Higher percentages of inorganic selenium were observed in primary consumers, detritivores, and filter feeders than in predatory insects. Among the organic forms of selenium, organic selenides constituted a major fraction in most organisms. A species modeled as trimethylselenonium was observed during the pupal stage of caddisflies. These results provide insights into how the insects cope with their toxic cargo, including how the selenium is biotransformed into less toxic forms and how it can be eliminated from the insects. More broadly, this study demonstrates the strengths of XAS to probe the effects of heavy elements at trace levels in insects from the field.« less

Distribution of selenium in zebrafish larvae after exposure to organic and inorganic selenium forms.

PubMed

Dolgova, N V; Hackett, M J; MacDonald, T C; Nehzati, S; James, A K; Krone, P H; George, G N; Pickering, I J

2016-03-01

Selenium is an essential micronutrient for many organisms, and in vertebrates has a variety of roles associated with protection from reactive oxygen species. Over the past two decades there have been conflicting reports upon human health benefits and detriments arising from consumption of selenium dietary supplements. Thus, early studies report a decrease in the incidence of certain types of cancer, whereas subsequent studies did not observe any anti-cancer effect, and adverse effects such as increased risks for type 2 diabetes have been reported. A possible contributing factor may be that different chemical forms of selenium were used in different studies. Using larval stage zebrafish (Danio rerio) as a model organism, we report a comparison of the toxicities and tissue selenium distributions of four different chemical forms of selenium. We find that the organic forms of selenium tested (Se-methyl-l-selenocysteine and l-selenomethionine) show considerably more toxicity than inorganic forms (selenite and selenate), and that this appears to be correlated with the level of bioaccumulation. Despite differences in concentrations, the tissue specific pattern of selenium accumulation was similar for the chemical forms tested; selenium was found to be highly concentrated in pigment (melanin) containing tissues especially for the organic selenium treatments, with lower concentrations in eye lens, yolk sac and heart. These results suggest that pigmented tissues might serve as a storage reservoir for selenium.

Selenium in diet

MedlinePlus

... Meats produced from animals that ate grains or plants found in selenium-rich soil have higher levels of selenium. Brewer's yeast, wheat germ, and enriched breads are also good sources of selenium.

Lignosulfonate-stabilized selenium nanoparticles and their deposition on spherical silica.

PubMed

Modrzejewska-Sikorska, Anna; Konował, Emilia; Klapiszewski, Łukasz; Nowaczyk, Grzegorz; Jurga, Stefan; Jesionowski, Teofil; Milczarek, Grzegorz

2017-10-01

We report a novel room-temperature synthesis of selenium nanoparticles, which for the first time uses lignosulfonate as a stabilizer. Various lignosulfonates obtained both from hardwood and softwood were tested. Selenium oxide was used as the precursor of zero-valent selenium. Three different reducers were tested - sodium borohydride, hydrazine and ascorbic acid - and the latter proved most effective in terms of the particle size and stability of the final colloid. The lignosulfonate-stabilized selenium nanoparticles had a negative zeta potential, dependent on pH, which for some lignosulfonates reached -50mV, indicating the excellent stability of the colloid. When spherical silica particles were introduced to the synthesis mixture, selenium nanoparticles were deposited on their surface. Additionally, star-like structures consisting of sharp selenium needles with silica cores were observed. After drying, the selenium-functionalized silica had a grey metallic hue. The method reported here is simple and cost-effective, and can be used for the preparation of large quantities of selenium colloids or the surface modification of other materials with selenium. Copyright © 2017 Elsevier B.V. All rights reserved.

Re-exposure of mallards to selenium after chronic exposure

USGS Publications Warehouse

Heinz, G.H.

1993-01-01

Adult male mallards (Anas platyrhynchos) were fed a control diet or a diet containing 15 ppm selenium as seleno-D,L-methionine for 21 weeks. After this initial exposure, the mallards were fed untreated food for 12 weeks, then were re-exposed to selenium at 100 ppm for five weeks. During re-exposure to 100 ppm selenium, the birds that had previously been exposed to 15 ppm selenium and those that had not previously been exposed did not differ in percentage of mortality (14.7 and 14.3%), weight loss in survivors (39.3 and 41.20%), selenium concentrations in the livers of survivors (35 and 53 ppm, wet weight), or selenium concentrations in the livers of birds that died (35 and 40 ppm, respectively). When the data from the birds that had previously been exposed to 15 ppm selenium were combined with the data from the birds that had not previously been exposed, selenium concentrations in the livers of birds that had died on the 100-ppm selenium treatment (38 ppm) did not differ from the concentrations in the livers of birds that had survived (43 ppm).

Reproduction of mallards following overwinter exposure to selenium

USGS Publications Warehouse

Heinz, G.H.; Fitzgerald, M.A.

1993-01-01

Forty pairs of mallards (Anas platyrhynchos) were fed 15 ppm selenium as selenomethionine for about 21 weeks during winter. Twenty pairs served as controls. At the end of 21 weeks, which coincided with the onset of the reproductive season, selenium treatment was ended. Four birds died while on selenium treatment. Treated females lost weight, and their egg-laying was delayed. Hatching success of some of the first eggs laid by selenium-treated females was lower than that of controls, and a few of these early eggs contained deformed embryos, but, after a period of about two weeks off the selenium-treated diet, reproductive success returned to a level comparable with that of controls. The return to normal reproductive success was the result of a corresponding decrease in selenium concentrations in eggs once selenium treatment ended.

[Assessment of efficiency of use of the developed supplement containing selenium on laboratory animals].

PubMed

Bazhenova, B A; Aslaliev, A D; Danilov, M B; Badmaeva, T M; Vtorushina, I A

2015-01-01

The article presents the results of a study of the effectiveness of wheat flour containing selenium in organic form. The organic form of trace element was achieved by transformation of selenium in selenium-methionine (Se-Met) at germination of wheat grains, moistened with a solution of sodium selenite. To determine the effectiveness of selenium- containing supplements experimental investigations were carried out on Long white rats with initial body weight 50 ± 2 g. The duration of the experiment was 30 days. The research model included four groups of animals: control group--animals were fed a complete vivarium diet; group 1--a model of selenium deficiency, which was achieved by feeding selenium-deficient food (grain growh in the Chita region of the Trans-Baikal Territory Zabaikalsky Krai); group 2--animals were administered selenium supplement in the form of enriched flour (0.025 µg Se per 50 g body weight of the animal) on the background of selenium-deficient diet; group 3--animals were treated with a high dose of selenium in the form of a solution of sodium selenite intragastrically through a tube (0.15 µg Se per 50 g body weight). Selenium-containing additive on the background of selenium-deficient diet had a positive impact on the appearance and behavior of animals, the body weight gain per head after 10 days in group 2 amounted to 47.9 g that was 4 fold larger than in rats of group 1. The study of selenium content showed that in the blood, liver, lungs and heart of rats treated with the additive on the background of selenium-deficient diet (group 2), selenium level did not differ from those in the control group and was within physiological norms. The experiment showed that selenium deficiency and rich in selenium rich diet has a significantly different effect on the studied parameters of oxidative-antioxidative status. The activity of blood glutathione peroxidase in animals of group 2 (did not differ from that in group 3) was almost 2 fold higher than in blood of control animals and was seven fold higher than that in blood of animals kept on selenium deficient diet (35.57 ± 3.36 µmol/g per 1 min) A similar dependence was established when studying the activity of glutathione reductase. It has been revealed thatthe oxidative-antioxidative status of animals from experimental groups 1 and 3 was lower than from control group and group 2. Thus, blood antioxidant activity in animals receiving diet with selenium deficiency and high dose of this trace element, was less than in the control group by 43.1 and 25.4%, respectively. Liver MDA level in animals kept on a diet with selenium deficiency exceeded the value of this indicator in the group 2 more than 1.5 fold (110.5 ± 10.70 vs. 72.5 ± 4.30 nmol/mg). When using selenium-containing supplement, this parameter decreased to the control level. In blood plasma of the animals of group 2 total antioxidant activity increased by about five times as compared with the indicators of animals kept on selenium-deficient diet, and was 25% higher than in control. Thus, the introduction of a selenium supplements in the deficient diet contributes to the development of endogenous antioxidants that suppress lipid oxidation. High biological effectiveness of supplements containing organic form of selenium has been proved.

Selective enrichment of metal-binding proteins based on magnetic core/shell microspheres functionalized with metal cations.

PubMed

Fang, Caiyun; Zhang, Lei; Zhang, Xiaoqin; Lu, Haojie

2015-06-21

Metal binding proteins play many important roles in a broad range of biological processes. Characterization of metal binding proteins is important for understanding their structure and biological functions, thus leading to a clear understanding of metal associated diseases. The present study is the first to investigate the effectiveness of magnetic microspheres functionalized with metal cations (Ca(2+), Cu(2+), Zn(2+) and Fe(3+)) as the absorbent matrix in IMAC technology to enrich metal containing/binding proteins. The putative metal binding proteins in rat liver were then globally characterized by using this strategy which is very easy to handle and can capture a number of metal binding proteins effectively. In total, 185 putative metal binding proteins were identified from rat liver including some known less abundant and membrane-bound metal binding proteins such as Plcg1, Acsl5, etc. The identified proteins are involved in many important processes including binding, catalytic activity, translation elongation factor activity, electron carrier activity, and so on.

Drumstick tree (Moringa oleifera) leaves as a source of dietary selenium, sulphur, and pro-vitamin A

USDA-ARS?s Scientific Manuscript database

The “drumstick tree” or “miracle tree” (Moringa oleifera) is well known for its high nutritional value. It grows well in tropical and sub-tropical regions, even on poor soils, is drought tolerant and produces abundant leaves high in protein (with a favorable amino acid balance), vitamins, minerals, ...

An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Republican River Basin: 1997-1999

USGS Publications Warehouse

May, T.W.; Walther, M.J.; Petty, J.D.; Fairchild, J.F.; Lucero, J.; Delvaux, M.; Manring, J.; Armbruster, M.; Hartman, D.

2001-01-01

The Republican River Basin of Colorado,Nebraska, and Kansas lies in a valley which contains PierreShale as part of its geological substrata. Selenium is anindigenous constituent in the shale and is readily leached intosurrounding groundwater. The Basin is heavily irrigated throughthe pumping of groundwater, some of which is selenium-contaminated, onto fields in agricultural production. Water,sediment, benthic invertebrates, and/or fish were collected from46 sites in the Basin and were analyzed for selenium to determinethe potential for food-chain bioaccumulation, dietary toxicity,and reproductive effects of selenium in biota. Resultingselenium concentrations were compared to published guidelines orbiological effects thresholds. Water from 38% of the sites (n = 18) contained selenium concentrations exceeding 5 μg L-1, which is reported to be a high hazard for selenium accumulation into the planktonic food chain. An additional 12 sites (26% of the sites) contained selenium in water between 3–5 μg L-1, constituting a moderate hazard. Selenium concentrations in sedimentindicated little to no hazard for selenium accumulation fromsediments into the benthic food chain. Ninety-five percent ofbenthic invertebrates collected exhibited selenium concentrationsexceeding 3 μg g-1, a level reported as potentially lethal to fish and birds that consume them. Seventy-five percent of fish collected in 1997, 90% in 1998, and 64% in 1999 exceeded 4 μg g-1selenium, indicating a high potential for toxicity andreproductive effects. However, examination of weight profilesof various species of collected individual fish suggestedsuccessful recruitment in spite of selenium concentrations thatexceeded published biological effects thresholds for health andreproductive success. This finding suggested that universalapplication of published guidelines for selenium may beinappropriate or at least may need refinement for systems similarto the Republican River Basin. Additional research is needed todetermine the true impact of selenium on fish and wildliferesources in the Basin.

Tighter Ligand Binding Can Compensate for Impaired Stability of an RNA-Binding Protein.

PubMed

Wallis, Christopher P; Richman, Tara R; Filipovska, Aleksandra; Rackham, Oliver

2018-06-15

It has been widely shown that ligand-binding residues, by virtue of their orientation, charge, and solvent exposure, often have a net destabilizing effect on proteins that is offset by stability conferring residues elsewhere in the protein. This structure-function trade-off can constrain possible adaptive evolutionary changes of function and may hamper protein engineering efforts to design proteins with new functions. Here, we present evidence from a large randomized mutant library screen that, in the case of PUF RNA-binding proteins, this structural relationship may be inverted and that active-site mutations that increase protein activity are also able to compensate for impaired stability. We show that certain mutations in RNA-protein binding residues are not necessarily destabilizing and that increased ligand-binding can rescue an insoluble, unstable PUF protein. We hypothesize that these mutations restabilize the protein via thermodynamic coupling of protein folding and RNA binding.

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

PubMed Central

Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.

2012-01-01

Abstract Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA[Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185–192. PMID:21854231

The von Hippel-Lindau (VHL) tumor-suppressor gene is down-regulated by selenium deficiency in Caco-2 cells and rat colon mucosa.

PubMed

Uthus, Eric; Begaye, Adrienne; Ross, Sharon; Zeng, Huawei

2011-08-01

To test the hypothesis that selenium affects DNA methylation and hence gene regulation, we employed a methylation array (Panomics) in the human colonic epithelial Caco-2 cell model. The array profiles DNA methylation from promoter regions of 82 human genes. After conditioning cells to repeatedly reduced concentrations of fetal bovine serum, a serum-free culture was established. Se-methylselenocysteine (SeMSC) was added at 0 (deficient Se) or 250 (control Se) nM to cells maintained in DMEM. After 7 days, cells were collected and stored at -80 °C until analysis; experiments were replicated three times. Glutathione peroxidase activity was significantly decreased in cells grown in low SeMSC. Cells grown in 250 nM SeMSC had maximal GPx activity. Genomic DNA from cells grown in the low-SeMSC media and media containing 250 nM SeMSC was incubated with methylation-binding protein followed by isolation of methylated DNA. The methylated DNA was labeled with biotin and hybridized to the methylation array. Thus, genes with promoter methylation will produce a higher chemiluminescence signal than those genes with no promoter methylation. Of the genes profiled, the von Hippel-Lindau (VHL) gene was most different as indicated by quantification following chemiluminescence detection demonstrating that the promoter region of VHL was hypermethylated in cells from the low-SeMSC media. To determine whether promoter methylation affected transcription, we isolated RNA from replicate samples and performed real-time RT PCR. VHL (mRNA) was down-regulated (fold change significantly <1) in cells grown in low SeMSC compared to cells grown in 250 nM SeMSC (control; fold change = 1). We also show that (mRNA) Vhl expression is significantly reduced in mucosa from rats fed a diet deficient in Se. Our results suggest that low Se status affects DNA promoter region methylation and that this can result in down-regulation of the tumor suppressor gene VHL.

Effect of selenium supplementation on pigeon reproductive performance, selenium concentration and antioxidant status.

PubMed

Wang, Y; Yang, H M; Cao, W; Li, Y B

2017-09-01

The effects of dietary supplementation of sodium selenite (SS) on the reproductive performance and the concentration of selenium, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined, and expression of glutathione peroxidase 4 (GPx4) and bone morphogenic protein 15 (BMP15) was evaluated. Paired pigeons (n = 864) were fed: T1 received no SS, while T2, T3, and T4 received 0.5, 1.0, and 1.5 mg of SS/kg of dry matter (DM), respectively. Treatments were performed in triplicate with 72 pairs in each replicate. The results showed that selenium supplementation significantly affected pigeon reproductive performance. Birds fed 1.0 mg of SS/kg displayed higher egg production (P > 0.05), higher birth rate, and lower dead sperm rate than the control group (P < 0.05). Selenium and biochemical analyses revealed a higher selenium concentration in the 1.5 mg of SS/kg group than in the control group (P < 0.05), while GSH-Px was higher in the 0.5 mg of SS/kg group than in the control group (P < 0.05). Neither the MDA nor the SOD content were affected significantly in liver, chest muscle, or leg muscle (P > 0.05); however, in plasma, MDA was lower in the control group (P < 0.05), while SOD was higher in the control group (P < 0.05). qRT-PCR results revealed up-regulation of GPx4 in hypothalamus, pituitary and testis tissues in supplemented groups (P < 0.05). However, expression in ovary differed; GPx4 mRNA levels were lower in the 1.5 mg of SS/kg and control groups than in the 1.0 or 0.5 mg of SS/kg groups (P < 0.05). Expression of BMP15 in the hypothalamus, pituitary, and testis tissues was unaffected (P > 0.05), while in ovary, BMP15 was down-regulated in the 1.5 mg of SS/kg group (P < 0.05). These results suggest pigeons supplemented with SS up-regulated GPx4, 1.0 mg of SS/kg exhibited superior reproductive performance, while 1.5 mg of SS/kg increased the selenium concentration, and 0.5 mg of SS/kg up-regulated GSH-Px activity. © 2017 Poultry Science Association Inc.

Red selenium nanoparticles and gray selenium nanorods as antibacterial coatings for PEEK medical devices.

PubMed

Wang, Qi; Mejía Jaramillo, Alejandra; Pavon, Juan J; Webster, Thomas J

2016-10-01

Bacterial infections are commonly found on various poly(ether ether ketone) (PEEK) medical devices (such as orthopedic instruments, spinal fusion devices, and segments in dialysis equipment), and thus, there is a significant need for introducing antibacterial properties to such materials. The objective of this in vitro study was to introduce antibacterial properties to PEEK medical devices by coating them with nanosized selenium. In this study, red selenium (an elemental form of selenium) nanoparticles were coated on PEEK medical devices through a quick precipitation method. Furthermore, with heat treatment at 100°C for 6 days, red selenium nanoparticles were transferred into gray selenium nanorods on the PEEK surfaces. Bacteria test results showed that both red and gray selenium-coated PEEK medical devices significantly inhibited the growth of Pseudomonas aeruginosa compared with uncoated PEEK after either 1, 2, or 3 days. Red selenium nanoparticle-coated PEEK showed less bacteria growth on its surface than gray selenium nanorod-coated PEEK after 3 days. This study demonstrated that red, and to a lesser extent gray, nanosized selenium could be used as potential antibacterial coatings to prevent bacteria function on PEEK medical devices. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1352-1358, 2016. © 2015 Wiley Periodicals, Inc.

Sequence-Based Prediction of RNA-Binding Residues in Proteins.

PubMed

Walia, Rasna R; El-Manzalawy, Yasser; Honavar, Vasant G; Dobbs, Drena

2017-01-01

Identifying individual residues in the interfaces of protein-RNA complexes is important for understanding the molecular determinants of protein-RNA recognition and has many potential applications. Recent technical advances have led to several high-throughput experimental methods for identifying partners in protein-RNA complexes, but determining RNA-binding residues in proteins is still expensive and time-consuming. This chapter focuses on available computational methods for identifying which amino acids in an RNA-binding protein participate directly in contacting RNA. Step-by-step protocols for using three different web-based servers to predict RNA-binding residues are described. In addition, currently available web servers and software tools for predicting RNA-binding sites, as well as databases that contain valuable information about known protein-RNA complexes, RNA-binding motifs in proteins, and protein-binding recognition sites in RNA are provided. We emphasize sequence-based methods that can reliably identify interfacial residues without the requirement for structural information regarding either the RNA-binding protein or its RNA partner.

Stunting, selenium deficiency and anemia are associated with poor cognitive performance in preschool children from rural Ethiopia.

PubMed

Gashu, Dawd; Stoecker, Barbara J; Bougma, Karim; Adish, Abdulaziz; Haki, Gulelat D; Marquis, Grace S

2016-04-12

Anthropometric characteristics and iron status affect cognitive performance in children. In addition, selenium can influence cognitive outcomes; protection of the brain from oxidative stress and its role in thyroid hormone metabolism are putative mechanisms. To investigate their association with cognitive performance, anthropometric indicators, iron biomarkers, and serum selenium of children (n = 541) of 54-60mo of age from rural Ethiopia were assessed. Cognitive assessment was conducted with the administration of two reasoning subtests of the Wechsler Preschool and Primary Scale of Intelligence and the school readiness test. Stunting was found in 41.4 % of children, 28.7 % were underweight, and 6.3 % were wasted. The mean score of stunted children was lower than that of non-stunted children on non-verbal reasoning (7.0 ± 3.2vs7.9 ± 3.1; p = 0.01) and the school readiness tests (4.3 ± 2.2 vs 3.3 ± 2.1; p < 0.001). Compared to non-anemic children, anemic children had lower score for the verbal reasoning test (9.5 ± 1.7 vs 8.9 ± 2.2; p = 0.02). However, except for hemoglobin, none of the iron biomarkers had significant associations with the cognitive score of the study children (p > 0.05). Selenium deficient children had lower scores on all cognitive tests than normal children (p < 0.05). The present study finding linking chronic undernutrition and micronutrient deficiency to cognitive deficits suggests the need for designing effective intervention programmes to control for protein energy malnutrition and micronutrient deficiency and address cognitive development in children.

Total selenium and selenium species in irrigation drain inflows to the Salton Sea, California, April and July 2007

USGS Publications Warehouse

May, Thomas W.; Walther, Michael J.; Saiki, Michael K.; Brumbaugh, William G.

2007-01-01

This report presents the results for two sampling periods during a 4-year monitoring survey to provide a characterization of selenium concentrations in selected irrigation drains flowing into the Salton Sea, California. Total selenium, selenium species, and total suspended solids were determined in water samples, and total selenium was determined in sediment, detritus, and biota that included algae, plankton, midge larvae (family, Chironomidae), and two fish species-western mosquitofish (Gambusia affinis), and sailfin molly (Poecilia latipinna). In addition, sediments were analyzed for percent total organic carbon and particle size. Total selenium concentrations in water for both sampling periods ranged from 1.43 to 47.1 micrograms per liter, predominately as selenate, which is typical of waters leached out of selenium-contaminated marine shales under alkaline and oxidizing conditions. Total selenium concentrations ranged from 0.88 to 20.2 micrograms per gram in biota, and from 0.15 to 28.9 micrograms per gram in detritus and sediment.

Selenium in fly ash

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutenmann, W.H.; Bache, C.A.; Youngs, W.D.

1976-03-05

Selenium, at concentrations exceeding 200 parts per million (ppM) (dry weight), has been found in white sweet clover voluntarily growing on beds of fly ash in central New York State. Guinea pigs fed such clover concentrated selenium in their tissues. The contents of the honey stomachs of bees foraging on this seleniferous clover contained negligible selenium. Mature vegetables cultured on 10 percent (by weight) fly ash-amended soil absorbed up to 1 ppM of selenium. Fly ashes from 21 states contained total selenium contents ranging from 1.2 to 16.5 ppM. Cabbage grown on soil containing 10 percent (by weight) of thesemore » fly ashes absorbed selenium (up to 3.7 ppM) in direct proportion (correlation coefficient r = .89) to the selenium concentration in the respective fly ash. Water, aquatic weeds, algae, dragonfly nymphs, polliwogs, and tissues of bullheads and muskrats from a fly ash-contaminated pond contained concentrations of selenium markedly elevated over those of controls.« less

Tissue distribution of selenium and effect of season and age on selenium content in roe deer from northwestern Poland.

PubMed

Pilarczyk, Bogumiła; Tomza-Marciniak, Agnieszka; Pilarczyk, Renata; Hendzel, Diana; Błaszczyk, Barbara; Bąkowska, Małgorzata

2011-06-01

The aim of the study was to compare selenium concentrations in different organs of roe deer from northwestern Poland. Samples of liver, kidneys, heart and lungs, collected from 74 roe deer shot during the hunting seasons of 2008-2009 in northwestern Poland, were studied. Selenium concentration in the organs was determined spectrofluorimetrically. Mean selenium concentration was 0.06 µg/g w.w. in the liver, 0.41 µg/g w.w. in the kidneys and 0.05 µg/g w.w. in the heart and lungs. Season had a significant effect on selenium concentration in the liver, kidneys, lungs and heart. In all the organs, the highest selenium concentration was found in spring and the lowest in autumn and winter. All animals studied were deficient in selenium. The low selenium concentration in the liver or heart can disturb their function, and in the future, it may be a factor contributing to the population decline of roe deer in the northwestern part of Poland.

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Nicastro, Holly L.; Dunn, Barbara K.

2013-01-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. PMID:23552052

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

PubMed Central

2010-01-01

Background Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein. PMID:20979600

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

PubMed

Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

2010-10-27

Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

Determining Membrane Protein-Lipid Binding Thermodynamics Using Native Mass Spectrometry.

PubMed

Cong, Xiao; Liu, Yang; Liu, Wen; Liang, Xiaowen; Russell, David H; Laganowsky, Arthur

2016-04-06

Membrane proteins are embedded in the biological membrane where the chemically diverse lipid environment can modulate their structure and function. However, the thermodynamics governing the molecular recognition and interaction of lipids with membrane proteins is poorly understood. Here, we report a method using native mass spectrometry (MS), to determine thermodynamics of individual ligand binding events to proteins. Unlike conventional methods, native MS can resolve individual ligand binding events and, coupled with an apparatus to control the temperature, determine binding thermodynamic parameters, such as for protein-lipid interactions. We validated our approach using three soluble protein-ligand systems (maltose binding protein, lysozyme, and nitrogen regulatory protein) and obtained similar results to those using isothermal titration calorimetry and surface plasmon resonance. We also determined for the first time the thermodynamics of individual lipid binding to the ammonia channel (AmtB), an integral membrane protein from Escherichia coli. Remarkably, we observed distinct thermodynamic signatures for the binding of different lipids and entropy-enthalpy compensation for binding lipids of variable chain length. Additionally, using a mutant form of AmtB that abolishes a specific phosphatidylglycerol (PG) binding site, we observed distinct changes in the thermodynamic signatures for binding PG, implying these signatures can identify key residues involved in specific lipid binding and potentially differentiate between specific lipid binding sites.

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study123

PubMed Central

Flax, Valerie L; Bentley, Margaret E; Combs, Gerald F; Chasela, Charles S; Kayira, Dumbani; Tegha, Gerald; Kamwendo, Debbie; Daza, Eric J; Fokar, Ali; Kourtis, Athena P; Jamieson, Denise J; van der Horst, Charles M; Adair, Linda S

2014-01-01

Background: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. Objective: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. Design: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Results: Overall, mean (±SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. Conclusions: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women. This trial was registered at clinicaltrials.gov as NCT00164736. PMID:24500152

Selenium Supranutrition: Are the Potential Benefits of Chemoprevention Outweighed by the Promotion of Diabetes and Insulin Resistance?

PubMed Central

Rocourt, Caroline R. B.; Cheng, Wen-Hsing

2013-01-01

Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. PMID:23603996

Proteome-wide Identification of Novel Ceramide-binding Proteins by Yeast Surface cDNA Display and Deep Sequencing.

PubMed

Bidlingmaier, Scott; Ha, Kevin; Lee, Nam-Kyung; Su, Yang; Liu, Bin

2016-04-01

Although the bioactive sphingolipid ceramide is an important cell signaling molecule, relatively few direct ceramide-interacting proteins are known. We used an approach combining yeast surface cDNA display and deep sequencing technology to identify novel proteins binding directly to ceramide. We identified 234 candidate ceramide-binding protein fragments and validated binding for 20. Most (17) bound selectively to ceramide, although a few (3) bound to other lipids as well. Several novel ceramide-binding domains were discovered, including the EF-hand calcium-binding motif, the heat shock chaperonin-binding motif STI1, the SCP2 sterol-binding domain, and the tetratricopeptide repeat region motif. Interestingly, four of the verified ceramide-binding proteins (HPCA, HPCAL1, NCS1, and VSNL1) and an additional three candidate ceramide-binding proteins (NCALD, HPCAL4, and KCNIP3) belong to the neuronal calcium sensor family of EF hand-containing proteins. We used mutagenesis to map the ceramide-binding site in HPCA and to create a mutant HPCA that does not bind to ceramide. We demonstrated selective binding to ceramide by mammalian cell-produced wild type but not mutant HPCA. Intriguingly, we also identified a fragment from prostaglandin D2synthase that binds preferentially to ceramide 1-phosphate. The wide variety of proteins and domains capable of binding to ceramide suggests that many of the signaling functions of ceramide may be regulated by direct binding to these proteins. Based on the deep sequencing data, we estimate that our yeast surface cDNA display library covers ∼60% of the human proteome and our selection/deep sequencing protocol can identify target-interacting protein fragments that are present at extremely low frequency in the starting library. Thus, the yeast surface cDNA display/deep sequencing approach is a rapid, comprehensive, and flexible method for the analysis of protein-ligand interactions, particularly for the study of non-protein ligands. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Determination of plasma protein binding rate of arctiin and arctigenin with ultrafiltration].

PubMed

Han, Xue-Ying; Wang, Wei; Tan, Ri-Qiu; Dou, De-Qiang

2013-02-01

To determine the plasma protein binding rate of arctiin and arctigenin. The ultrafiltration combined with HPLC was employed to determine the plasma protein binding rate of arctiin and arctigenin as well as rat plasma and healthy human plasma proteins. The plasma protein binding rate of arctiin with rat plasma at the concentrations of 64. 29, 32.14, 16.07 mg x L(-1) were (71.2 +/- 2.0)%, (73.4 +/- 0.61)%, (78.2 +/- 1.9)%, respectively; while the plasma protein binding rate of arctiin with healthy human plasma at the above concentrations were (64.8 +/- 3.1)%, (64.5 +/- 2.5)%, (77.5 +/- 1.7)%, respectively. The plasma protein binding rate of arctigenin with rat plasma at the concentrations of 77.42, 38.71, 19.36 mg x L(-1) were (96.7 +/- 0.41)%, (96.8 +/- 1.6)%, (97.3 +/- 0.46)%, respectively; while the plasma protein binding rate of arctigenin with normal human plasma at the above concentrations were (94.7 +/- 3.1)%, (96.8 +/- 1.6)%, (97.9 +/- 1.3)%, respectively. The binding rate of arctiin with rat plasma protein was moderate, which is slightly higher than the binding rate of arctiin with healthy human plasma protein. The plasma protein binding rates of arctigenin with both rat plasma and healthy human plasma are very high.

Molecular and neurochemical biomarkers in Arctic beluga whales (Delphinapterus leucas) were correlated to brain mercury and selenium concentrations.

PubMed

Ostertag, Sonja K; Shaw, Alyssa C; Basu, Niladri; Chan, Hing Man

2014-10-07

Mercury (Hg) concentrations have increased in western Arctic beluga whales (Delphinapterus leucas) since the industrial revolution. Methylmercruy (MeHg) is a known neurotoxicant, yet little is known about the risk of exposure for beluga whales. Selenium (Se) has been linked to demethylation of MeHg in cetaceans, but its role in attenuating Hg toxicity in beluga whales is poorly understood. The objective of this study is to explore relationships between Hg and Se concentrations and neurochemical biomarkers in different brain regions of beluga whales in order to assess potential neurotoxicological risk of Hg exposure in this population. Brain tissue was sampled from hunter-harvested beluga whales from the western Canadian Arctic in 2008 and 2010. Neurochemical and molecular biomarkers were measured with radioligand binding assays and quantitative PCR, respectively. Total Hg (HgT) concentration ranged from 2.6-113 mg kg(-1) dw in temporal cortex. Gamma-amminobutyric acid type A receptor (GABAA-R) binding in the cerebellum was negatively associated with HgT, MeHg and total Se (SeT) concentrations (p ≤ 0.05). The expression of mRNA for GABAA-R subunit α2 was negatively associated with HgT and MeHg (p ≤ 0.05). Furthermore, GABAA-R binding was positively correlated to mRNA expression for GABAA-R α2 subunit, and negatively correlated to the expression of mRNA for GABAA-R α4 subunit (p ≤ 0.05). The expression of N-methyl-d-aspartate receptor (NMDA-R) subunit 2b mRNA expression was negatively associated with iHglabile concentration in the cerebellum (p ≤ 0.05). Variation of molecular and/or biochemical components of the GABAergic and glutamatergic signaling pathways were associated with MeHg exposure in beluga whales. Our results show that MeHg exposure is associated with neurochemical variation in the cerebellum of beluga whales and Se may partially protect from MeHg-associated neurotoxicity.

[The relationship between selenium and gastrointestinal inflammatory diseases].

PubMed

Nagy, Dániel Tamás; Fülesdi, Béla; Hallay, Judit

2013-10-13

The cell-membrane toxicity of reactive oxygen and nitrogen species (RONS) plays an increasing role in the pathomechanism of gastrointestinal tract diseases. Trace elements are important parts of antioxidant protecting system, especially the selenium (Se), which, in the form of glutathione peroxidase contributes to the immunity of the gut (GALT). Due to the absorptional disorders and consequent malnutrition observed in the course of inflammatory bowel diseases (IBD) an important role is associated with nutritional therapy, including energy-, protein- and trace element-support. Human studies show, that IBD is mostly accompanied by lower serum Se concentrations, reduced antoxidant and increased proinflammatory activity. Adequate Se-replacement may reduce the severity of organ failure and infections, but not mortality. However, it is encouraging that in animal studies obvious preventive effect of Se has been found on IBD and chronic inflammation induced colon cancer .

Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women1

PubMed Central

Mao, Jinyuan; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher WG; Ahmadi, Kourosh R; Rayman, Margaret P

2016-01-01

Background: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]. Objective: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 μg/d. Design: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation. Results: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579. Conclusions: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591. PMID:26675765

Selenium Recycling in the United States in 2004

USGS Publications Warehouse

George, Micheal W.; Wagner, Lorie A.

2009-01-01

The vast majority of selenium consumption in the United States is in dissipative uses, such as alloys, animal feeds, fertilizers, glass decolorizer, and pigments. The nondissipative use as a photoreceptor for xerographic copiers is declining. As a result of a lack of a substantial supply of selenium-containing scrap, there are no longer selenium recycling facilities in the United States. Selenium-containing materials collected for recycling, primarily selenium-containing photocopier drums, are exported for processing in other countries. Of the estimated 350 metric tons (t) of selenium products that went to the U.S. market in 2004, an estimated 300 t went to dissipative uses. An estimated 4 t was recovered from old scrap and exported for recycling.

Selenium species in selenium fortified dietary supplements.

PubMed

Niedzielski, Przemyslaw; Rudnicka, Monika; Wachelka, Marcin; Kozak, Lidia; Rzany, Magda; Wozniak, Magdalena; Kaskow, Zaneta

2016-01-01

This article presents a study of dietary supplements available on the Polish market. The supplements comprised a large group of products with selenium content declared by the producer. The study involved determination of dissolution time under different conditions and solubility as well as content and speciation of selenium. The total content was determined as well as organic selenium and the inorganic forms Se(IV) and Se(VI). The organic selenium content was calculated as the difference between total Se and inorganic Se. The values obtained were compared with producers' declarations. The work is the first such study of selenium supplements available on the market of an EU Member State. Copyright © 2015 Elsevier Ltd. All rights reserved.

Defining the Optimal Selenium Dose for Prostate Cancer Risk Reduction: Insights from the U-Shaped Relationship Between Selenium Status, DNA Damage, and Apoptosis

USDA-ARS?s Scientific Manuscript database

Our work in dogs has revealed a U-shaped dose response between selenium status and prostatic DNA damage that remarkably parallels the relationship between dietary selenium and prostate cancer risk in men, suggesting that more selenium is not necessarily better. Herein, we extend this canine work to ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caberoy, Nora B.; Zhou, Yixiong; Alvarado, Gabriela

To efficiently elucidate the biological roles of phosphatidylserine (PS), we developed open-reading-frame (ORF) phage display to identify PS-binding proteins. The procedure of phage panning was optimized with a phage clone expressing MFG-E8, a well-known PS-binding protein. Three rounds of phage panning with ORF phage display cDNA library resulted in {approx}300-fold enrichment in PS-binding activity. A total of 17 PS-binding phage clones were identified. Unlike phage display with conventional cDNA libraries, all 17 PS-binding clones were ORFs encoding 13 real proteins. Sequence analysis revealed that all identified PS-specific phage clones had dimeric basic amino acid residues. GST fusion proteins were expressedmore » for 3 PS-binding proteins and verified for their binding activity to PS liposomes, but not phosphatidylcholine liposomes. These results elucidated previously unknown PS-binding proteins and demonstrated that ORF phage display is a versatile technology capable of efficiently identifying binding proteins for non-protein molecules like PS.« less

Is selenium supplementation in autoimmune thyroid diseases justified?

PubMed

Winther, Kristian H; Bonnema, Steen J; Hegedüs, Laszlo

2017-10-01

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.

Microarray Data Mining for Potential Selenium Targets in Chemoprevention of Prostate Cancer

PubMed Central

ZHANG, HAITAO; DONG, YAN; ZHAO, HONGJUAN; BROOKS, JAMES D.; HAWTHORN, LESLEYANN; NOWAK, NORMA; MARSHALL, JAMES R.; GAO, ALLEN C.; IP, CLEMENT

2008-01-01

Background A previous clinical trial showed that selenium supplementation significantly reduced the incidence of prostate cancer. We report here a bioinformatics approach to gain new insights into selenium molecular targets that might be relevant to prostate cancer chemoprevention. Materials and Methods We first performed data mining analysis to identify genes which are consistently dysregulated in prostate cancer using published datasets from gene expression profiling of clinical prostate specimens. We then devised a method to systematically analyze three selenium microarray datasets from the LNCaP human prostate cancer cells, and to match the analysis to the cohort of genes implicated in prostate carcinogenesis. Moreover, we compared the selenium datasets with two datasets obtained from expression profiling of androgen-stimulated LNCaP cells. Results We found that selenium reverses the expression of genes implicated in prostate carcinogenesis. In addition, we found that selenium could counteract the effect of androgen on the expression of a subset obtained from androgen-regulated genes. Conclusions The above information provides us with a treasure of new clues to investigate the mechanism of selenium chemoprevention of prostate cancer. Furthermore, these selenium target genes could also serve as biomarkers in future clinical trials to gauge the efficacy of selenium intervention. PMID:18548127

Total selenium and selenium species in irrigation drain inflows to the Salton Sea, California, October 2007 and January 2008

USGS Publications Warehouse

May, Thomas W.; Walther, Michael J.; Saiki, Michael K.; Brumbaugh, William G.

2008-01-01

This report presents the results for two sampling periods (October 2007 and January 2008) during a 4-year monitoring program to characterize selenium concentrations in selected irrigation drains flowing into the Salton Sea, California. Total selenium, selenium species (selenite, selenate, organoselenium), and total suspended solids were determined in water samples, and total selenium was determined in sediment, detritus, and biota that included algae, plankton, midge larvae (family, Chironomidae), and two fish species?western mosquitofish (Gambusia affinis) and sailfin molly (Poecilia latipinna). In addition, sediments were analyzed for percent total organic carbon and particle size. Mean total selenium concentrations in water for both sampling periods ranged from 0.97 to 64.5 micrograms per liter, predominately as selenate, which is typical of waters where selenium is leached out of selenium-containing marine shales and associated soils under alkaline and oxidizing conditions. Total selenium concentrations (micrograms per gram dry weight) ranged as follows: algae, 0.95 to 5.99; plankton, 0.15 to 19.3; midges, 1.39 to 15.4; fish, 3.71 to 25.1; detritus, 0.85 to 21.7; sediment, 0.32 to 7.28.

Total selenium and selenium species in irrigation drain inflows to the Salton Sea, California, April and July 2008

USGS Publications Warehouse

May, Thomas W.; Walther, Michael J.; Saiki, Michael K.; Brumbaugh, William G.

2009-01-01

This report presents the results for two sampling periods (April 2008 and July 2008) during a 4-year monitoring program to characterize selenium concentrations in selected irrigation drains flowing into the Salton Sea, California. Total selenium, selenium species (dissolved selenite, selenate, organoselenium), and total suspended solids were determined in water samples and total selenium was determined in water column particulates and in sediment, detritus, and biota that included algae, plankton, midge larvae (family, Chironomidae), and two fish species - western mosquitofish (Gambusia affinis) and sailfin molly (Poecilia latipinna). In addition, sediments were analyzed for percent total organic carbon and particle size. Mean total selenium concentrations in water for both sampling periods ranged from 1.93 to 44.2 micrograms per liter, predominately as selenate, which is typical of waters where selenium is leached out of selenium-containing marine shales and associated soils under alkaline and oxidizing conditions. Total selenium concentrations (micrograms per gram dry weight) ranged as follows: algae, 0.75 to 3.39; plankton, 0.88 to 4.03; midges, 2.52 to 44.3; fish, 3.37 to 18.9; detritus, 1.11 to 13.6; sediment, 0.11 to 8.93.

Total selenium and selenium species in irrigation drain inflows to the Salton Sea, California, October 2008 and January 2009

USGS Publications Warehouse

May, Thomas W.; Walther, Michael J.; Saiki, Michael K.; Brumbaugh, William G.

2009-01-01

This report presents the results for two sampling periods (October 2008 and January 2009) during a 4-year monitoring program to characterize selenium concentrations in selected irrigation drains flowing into the Salton Sea, California. Total selenium, selenium species (dissolved selenite, selenate, organoselenium), and total suspended solids were determined in water samples. Total selenium also was determined in water column particulates and in sediment, detritus, and biota that included algae, plankton, midge larvae (family, Chironomidae), and two fish species (western mosquitofish, Gambusia affinis, and sailfin molly, Poecilia latipinna). In addition, sediments were analyzed for percent total organic carbon and particle size. Mean total selenium concentrations in water for both sampling periods ranged from 1.00 to 33.6 micrograms per liter, predominately as selenate, which is typical of waters where selenium is leached out of selenium-containing marine shales and associated soils under alkaline and oxidizing conditions. Total selenium concentrations (micrograms per gram dry weight) ranged as follows: algae, 1.52 to 8.26; plankton, 0.79 to 3.66; midges, 2.68 to 50.6; fish, 3.09 to 30.4; detritus, 1.78 to 58.0; and sediment, 0.42 to 10.0.

Selenium and the control of thyroid hormone metabolism.

PubMed

Köhrle, Josef

2005-08-01

Thyroid hormone synthesis, metabolism and action require adequate availability of the essential trace elements iodine and selenium, which affect homeostasis of thyroid hormone-dependent metabolic pathways. The three selenocysteine-containing iodothyronine deiodinases constitute a novel gene family. Selenium is retained and deiodinase expression is maintained at almost normal levels in the thyroid gland, the brain and several other endocrine tissues during selenium deficiency, thus guaranteeing adequate local and systemic levels of the active thyroid hormone T(3). Due to their low tissue concentrations and their mRNA SECIS elements deiodinases rank high in the cellular and tissue-specific hierarchy of selenium distribution among various selenoproteins. While systemic selenium status and expression of abundant selenoproteins (glutathione peroxidase or selenoprotein P) is already impaired in patients with cancer, disturbed gastrointestinal resorption, unbalanced nutrition or patients requiring intensive care treatment, selenium-dependent deiodinase function might still be adequate. However, disease-associated alterations in proinflammatory cytokines, growth factors, hormones and pharmaceuticals modulate deiodinase isoenzyme expression independent from altered selenium status and might thus pretend causal relationships between systemic selenium status and altered thyroid hormone metabolism. Limited or inadequate supply of both trace elements, iodine and selenium, leads to complex rearrangements of thyroid hormone metabolism enabling adaptation to unfavorable conditions.

Reproductive status of western mosquitofish inhabiting selenium- contaminated waters in the Grassland Water District, Merced County, California

USGS Publications Warehouse

Saiki, M.K.; Martin, B.A.; May, T.W.

2004-01-01

This study was implemented to determine if western mosquitofish (Gambusia affinis) populations in the Grassland Water District suffer from impaired reproduction because of seleniferous inflows of agricultural drainwater from the Grassland Bypass Project. During June to July 2001, laboratory trials with pregnant female fish collected from two seleniferous treatment sites exposed to selenium-laden drainwater and two nonseleniferous reference sites yielded fry that averaged >96% survival at birth. In addition, none of the newborn fry exhibited evidence of teratogenesis, a typical consequence of selenium toxicity. Chemical analysis of postpartum female fish and their newborn fry indicated that mosquitofish from seleniferous sites accumulated relatively high body burdens of selenium (3.96 to 17.5 μg selenium/g in postpartum female fish and 5.35 to 29.2 μg selenium/g in their fry), whereas those from nonseleniferous sites contained lower body burdens (0.40 to 2.72 μg selenium/g in postpartum female fish and 0.61 to 4.68 μg selenium/g in their fry). Collectively, these results strongly suggest that mosquitofish inhabiting selenium-contaminated waters are not experiencing adverse reproductive effects at current levels of selenium exposure.

[Selenium supplementation trials for cancer prevention and the subsequent risk of type 2 diabetes mellitus: selenium and vitamin E cancer prevention trial and after].

PubMed

Koyama, Hiroshi; Mutakin; Abdulah, Rizky; Yamazaki, Chiho; Kameo, Satomi

2013-01-01

The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 μg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.

Effect of dietary selenium and omega-3 fatty acids on muscle composition and quality in broilers

PubMed Central

Haug, Anna; Eich-Greatorex, Susanne; Bernhoft, Aksel; Wold, Jens P; Hetland, Harald; Christophersen, Olav A; Sogn, Trine

2007-01-01

Background Human health may be improved if dietary intakes of selenium and omega-3 fatty acids are increased. Consumption of broiler meat is increasing, and the meat content of selenium and omega-3 fatty acids are affected by the composition of broiler feed. A two-way analyses of variance was used to study the effect of feed containing omega-3 rich plant oils and selenium enriched yeast on broiler meat composition, antioxidation- and sensory parameters. Four different wheat-based dietary treatments supplemented with 5% rapeseed oil or 4% rapeseed oil plus 1% linseed oil, and either 0.50 mg selenium or 0.84 mg selenium (organic form) per kg diet was fed to newly hatched broilers for 22 days. Results The different dietary treatments gave distinct different concentrations of selenium and fatty acids in thigh muscle; one percent linseed oil in the diet increased the concentration of the omega-3 fatty acids 18:3, 20:5 and 22:5, and 0.84 mg selenium per kg diet gave muscle selenium concentration at the same level as is in fish muscle (0.39 mg/kg muscle). The high selenium intake also resulted in increased concentration of the long-chain omega-3 fatty acids EPA (20:5), DPA (22:5) and DHA (22:6), thus it may be speculated if high dietary selenium might have a role in increasing the concentration of EPA, DPA and DHA in tissues after intake of plant oils contning omega-3 fatty acids. Conclusion Moderate modifications of broiler feed may give a healthier broiler meat, having increased content of selenium and omega-3 fatty acids. High intakes of selenium (organic form) may increase the concentration of very long-chain omega-3 fatty acids in muscle. PMID:17967172

Detailed study of selenium in soil, water, bottom sediment, and biota in the Sun River Irrigation Project, Freezout Lake Wildlife Management Area, and Benton Lake National Wildlife Refuge, west-central Montana, 1990-92

USGS Publications Warehouse

Nimick, D.A.; Lambing, J.H.; Palawski, D.U.; Malloy, J.C.

1996-01-01

Selenium and other constituents are adversely affecting water quality and creating a potential hazard to wildlife in several areas of the Sun River Irrigation Project, Freezout Lake Wildlife Management Area, and Benton Lake National Wildlife Refuge in west-central Montana. Selenium derived from Cretaceous shale and Tertiary and Quaternary deposits containing shale detritus is transported in the oxic shallow ground-water systems. At Freezout Lake Wildlife Management Area, drainage from irrigated glacial deposits is the primary source of selenium; drainage from non-irrigated farmland is a significant source locally. Benton Lake generally receives more selenium from natural runoff from its non-irrigated basin than from the trans-basin diversion of irrigation return flow. Selenium has accumulated in aquatic plants and invertebrates, fish, and water birds, particularly in wetlands that receive the largest selenium loads. Although selenium residues in biological tissue from some wetland units exceeded biological risk levels, water-bird reproduction generally has not been impaired. The highest selenium residues in biota commonly occurred in samples from Priest Butte Lakes, which also had the highest selenium concentration in wetland water. Selenium concentrations in all invertebrate samples from Priest Butte Lakes and the south end of Freezeout Lake exceeded the critical dietary threshold for water birds. Selenium delivered to wetlands accumulates in bottom sediment, predominantly in near-shore areas. Potential impacts to water quality, and presumably biota, may be greatest near the mouths of inflows. Most selenium delivered to wetlands will continue to accumulate in bottom sediment and biota.

Preliminary assessment of sources, distribution, and mobility of selenium in the San Joaquin Valley, California

USGS Publications Warehouse

Gilliom, R.J.

1989-01-01

Selenium in tile drain water from parts of the western San Joaquin Valley, California, has adversely affected fish and waterfowl where drain water was impounded. Soils in these drained areas were derived from Coast Range marine sedimentary formations, were naturally saline and probably contained abundant soluble selenium. Decades of irrigation have redistributed the most soluble forms of selenium from the soil into groundwater and have caused the water table to rise 1 to 4 ft/year. Selenium in shallow groundwater has been further concentrated because of evapotranspiration. The rising water table has caused a large area of farmland to require artificial drainage of groundwater that contains high concentrations of selenium. The present areal distribution of selenium in shallow groundwater reflects the natural distribution of saline soils. The depth distribution of selenium in groundwater reflects the history of irrigation. The highest concentrations of selenium in groundwater (50 to more than 1,000 micrograms/L) are in a zone of variable thickness located between 20 and 150 ft below the water table. The toxic water in this zone was recharged during the first few decades of irrigation. The large volume of high selenium groundwater makes it desirable to leave this water where it is, rather than bring it to the land surface or allow it to move into parts of the aquifer that may be used for water supply. Selenium concentrations in the San Joaquin River depend on the magnitude of the selenium load from drain water and dilution by water with low concentrations of selenium from all other sources of streamflow. The San Joaquin Valley is a regional-scale example of how manipulation of the hydrologic system can cause water quality problems if naturally occurring toxic substances are mobilized. (USGS)

Isolation and characterizations of oxalate-binding proteins in the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roop-ngam, Piyachat; Chaiyarit, Sakdithep; Pongsakul, Nutkridta

Highlights: Black-Right-Pointing-Pointer The first large-scale characterizations of oxalate-binding kidney proteins. Black-Right-Pointing-Pointer The recently developed oxalate-conjugated EAH Sepharose 4B beads were applied. Black-Right-Pointing-Pointer 38 forms of 26 unique oxalate-binding kidney proteins were identified. Black-Right-Pointing-Pointer 25/26 (96%) of identified proteins had 'L-x(3,5)-R-x(2)-[AGILPV]' domain. -- Abstract: Oxalate-binding proteins are thought to serve as potential modulators of kidney stone formation. However, only few oxalate-binding proteins have been identified from previous studies. Our present study, therefore, aimed for large-scale identification of oxalate-binding proteins in porcine kidney using an oxalate-affinity column containing oxalate-conjugated EAH Sepharose 4B beads for purification followed by two-dimensional gel electrophoresis (2-DE) tomore » resolve the recovered proteins. Comparing with those obtained from the controlled column containing uncoupled EAH-Sepharose 4B (to subtract the background of non-specific bindings), a total of 38 protein spots were defined as oxalate-binding proteins. These protein spots were successfully identified by quadrupole time-of-flight mass spectrometry (MS) and/or tandem MS (MS/MS) as 26 unique proteins, including several nuclear proteins, mitochondrial proteins, oxidative stress regulatory proteins, metabolic enzymes and others. Identification of oxalate-binding domain using the PRATT tool revealed 'L-x(3,5)-R-x(2)-[AGILPV]' as a functional domain responsible for oxalate-binding in 25 of 26 (96%) unique identified proteins. We report herein, for the first time, large-scale identification and characterizations of oxalate-binding proteins in the kidney. The presence of positively charged arginine residue in the middle of this functional domain suggested its significance for binding to the negatively charged oxalate. These data will enhance future stone research, particularly on stone modulators.« less

Selenium effect on selenoprotein transcriptome in chondrocytes.

PubMed

Yan, Jidong; Zheng, Yuewen; Min, Zixin; Ning, Qilan; Lu, Shemin

2013-04-01

Selenium is an essential micronutrient and exerts its biological functions predominantly through selenoproteins. Selenium deficiency is associated with cartilage function. This study demonstrated that all 24 selenoprotein transcripts in mouse genome were detectable in ATDC5 chondrocytes except deiodinase 1 (DIO1), DIO2, and selenoprotein V (Sel V), while all 25 selenoprotein transcripts in human genome were detectable in C28/I2 chondrocytes except glutathione peroxidase 6 (GPx6) and DIO1. In addition, gene expression of five selenoproteins (GPx1, Sel H, Sel N, Sel P, and Sel W) was up-regulated and two selenoproteins (SPS2 and Sel O) was down-regulated by sodium selenite (Se) in both ATDC5 and C28/I2 cells. Gene expression of six selenoproteins (TrxR1, Sel I, Sel M, Sel R, Sel S, Sel T) and one selenoprotein (GPx3) was up-regulated by Se in ATDC5 and C28/I2 cells, respectively. Gene expression of one selenoprotein (TrxR2) was down-regulated by Se only in ATDC5 cells. Further transcription inhibition assay showed that both transcriptional and posttranscriptional mechanisms involved in Se-regulated gene expression of GPx1, TrxR1, TrxR2, SPS2, Sel O, and Sel S. However, Se-regulated gene expression of Sel H, Sel I, Sel M, Sel N, Sel P, Sel R, Sel T, and Sel W mainly at posttranscriptional level. Moreover, new protein synthesis inhibition assay indicated that Se-mediated new protein synthesis also played roles in Se-regulated gene expression of GPx1, TrxR1, TrxR2, Sel H, Sel O, Sel P, Sel R, and Sel W. In summary, this study described the selenoprotein transcriptome, Se-regulated selenoproteins and possible mechanisms involved in chondrocytes.

The effect of sulfate on selenate bioaccumulation in two freshwater primary producers: A duckweed (Lemna minor) and a green alga (Pseudokirchneriella subcapitata).

PubMed

Lo, Bonnie P; Elphick, James R; Bailey, Howard C; Baker, Josh A; Kennedy, Christopher J

2015-12-01

Predicting selenium bioaccumulation is complicated because site-specific conditions, including the ionic composition of water, affect the bioconcentration of inorganic selenium into the food web. Selenium tissue concentrations were measured in Lemna minor and Pseudokirchneriella subcapitata following exposure to selenate and sulfate. Selenium accumulation differed between species, and sulfate reduced selenium uptake in both species, indicating that ionic constituents, in particular sulfate, are important in modifying selenium uptake by primary producers. © 2015 SETAC.

Total selenium in irrigation drain inflows to the Salton Sea, California, April 2009

USGS Publications Warehouse

May, Thomas W.; Walther, Michael J.; Saiki, Michael K.; Brumbaugh, William G.

2009-01-01

This report presents the results for the final sampling period (April 2009) of a 4-year monitoring program to characterize selenium concentrations in selected irrigation drains flowing into the Salton Sea, California. Total selenium and total suspended solids were determined in water samples. Total selenium, percent total organic carbon, and particle size were determined in sediments. Mean total selenium concentrations in water ranged from 0.98 to 22.9 micrograms per liter. Total selenium concentrations in sediment ranged from 0.078 to 5.0 micrograms per gram dry weight.

Structural Analysis of Semi-specific Oligosaccharide Recognition by a Cellulose-binding Protein of Thermotoga maritima Reveals Adaptations for Functional Diversification of the Oligopeptide Periplasmic Binding Protein Fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuneo, Matthew J.; Beese, Lorena S.; Hellinga, Homme W.

Periplasmic binding proteins (PBPs) constitute a protein superfamily that binds a wide variety of ligands. In prokaryotes, PBPs function as receptors for ATP-binding cassette or tripartite ATP-independent transporters and chemotaxis systems. In many instances, PBPs bind their cognate ligands with exquisite specificity, distinguishing, for example, between sugar epimers or structurally similar anions. By contrast, oligopeptide-binding proteins bind their ligands through interactions with the peptide backbone but do not distinguish between different side chains. The extremophile Thermotoga maritima possesses a remarkable array of carbohydrate-processing metabolic systems, including the hydrolysis of cellulosic polymers. Here, we present the crystal structure of a T.more » maritima cellobiose-binding protein (tm0031) that is homologous to oligopeptide-binding proteins. T. maritima cellobiose-binding protein binds a variety of lengths of {beta}(1 {yields} 4)-linked glucose oligomers, ranging from two rings (cellobiose) to five (cellopentaose). The structure reveals that binding is semi-specific. The disaccharide at the nonreducing end binds specifically; the other rings are located in a large solvent-filled groove, where the reducing end makes several contacts with the protein, thereby imposing an upper limit of the oligosaccharides that are recognized. Semi-specific recognition, in which a molecular class rather than individual species is selected, provides an efficient solution for the uptake of complex mixtures.« less

Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3′′)(9) adenyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yang; Näsvall, Joakim; Wu, Shiying

The crystal structure of the aminoglycoside-adenylating enzyme AadA is reported together with functional experiments providing insights into its oligomeric state, ligand binding and catalysis. Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3′′)(9) adenyltransferase, AadA from Salmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 Å resolution. AadA consists of a nucleotidyltransferase domain and an α-helical bundlemore » domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis. In vivo resistance and in vitro binding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding.« less

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

PubMed

Brannan, Kristopher W; Jin, Wenhao; Huelga, Stephanie C; Banks, Charles A S; Gilmore, Joshua M; Florens, Laurence; Washburn, Michael P; Van Nostrand, Eric L; Pratt, Gabriel A; Schwinn, Marie K; Daniels, Danette L; Yeo, Gene W

2016-10-20

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma Selenium Biomarkers in Low Income Black and White Americans from the Southeastern United States

PubMed Central

Hargreaves, Margaret K.; Liu, Jianguo; Buchowski, Maciej S.; Patel, Kushal A.; Larson, Celia O.; Schlundt, David G.; Kenerson, Donna M.; Hill, Kristina E.; Burk, Raymond F.; Blot, William J.

2014-01-01

Biomarkers of selenium are necessary for assessing selenium status in humans, since soil variation hinders estimation of selenium intake from foods. In this study, we measured the concentration of plasma selenium, selenoprotein P (SEPP1), and glutathione peroxidase (GPX3) activity and their interindividual differences in 383 low-income blacks and whites selected from a stratified random sample of adults aged 40–79 years, who were participating in a long-term cohort study in the southeastern United States (US). We assessed the utility of these biomarkers to determine differences in selenium status and their association with demographic, socio-economic, dietary, and other indicators. Dietary selenium intake was assessed using a validated food frequency questionnaire designed for the cohort, matched with region-specific food selenium content, and compared with the US Recommended Dietary Allowances (RDA) set at 55 µg/day. We found that SEPP1, a sensitive biomarker of selenium nutritional status, was significantly lower among blacks than whites (mean 4.4±1.1 vs. 4.7±1.0 mg/L, p = 0.006), with blacks less than half as likely to have highest vs. lowest quartile SEPP1 concentration (Odds Ratio (OR) 0.4, 95% Confidence Interval (CI) 0.2–0.8). The trend in a similar direction was observed for plasma selenium among blacks and whites, (mean 115±15.1 vs. 118±17.7 µg/L, p = 0.08), while GPX3 activity did not differ between blacks and whites (136±33.3 vs. 132±33.5 U/L, p = 0.320). Levels of the three biomarkers were not correlated with estimated dietary selenium intake, except for SEPP1 among 10% of participants with the lowest selenium intake (≤57 µg/day). The findings suggest that SEPP1 may be an effective biomarker of selenium status and disease risk in adults and that low selenium status may disproportionately affect black and white cohort participants. PMID:24465457

Biological alkylation and colloid formation of selenium in methanogenic UASB reactors.

PubMed

Lenz, Markus; Smit, Martijn; Binder, Patrick; van Aelst, Adriaan C; Lens, Piet N L

2008-01-01

Bioalkylation and colloid formation of selenium during selenate removal in upflow anaerobic sludge bed (UASB) bioreactors was investigated. The mesophilic (30 degrees C) UASB reactor (pH = 7.0) was operated for 175 d with lactate as electron donor at an organic loading rate of 2 g COD L(-1) d(-1) and a selenium loading rate of 3.16 mg Se L(-1) d(-1). Combining sequential filtration with ion chromatographic analysis for selenium oxyanions and solid phase micro extraction gas chromatography mass spectrometry (SPME-GC-MS) for alkylated selenium compounds allowed to entirely close the selenium mass balance in the liquid phase for most of the UASB operational runtime. Although selenate was removed to more than 98.6% from the liquid phase, a less efficient removal of dissolved selenium was observed due to the presence of dissolved alkylated selenium species (dimethylselenide and dimethyldiselenide) and colloidal selenium particles in the effluent. The alkylated and the colloidal fractions contributed up to 15 and 31%, respectively, to the dissolved selenium concentration. The size fractions of the colloidal dispersion were: 4 to 0.45 mum: up to 21%, 0.45 to 0.2 mum: up to 11%, and particles smaller than 0.2 mum: up to 8%. Particles of 4 to 0.45 mum were formed in the external settler, but did not settle. SEM-EDX analysis showed that microorganisms form these selenium containing colloidal particles extracellularly on their surface. Lowering the temperature by 10 degrees C for 6 h resulted in drastically reduced selenate removal efficiencies (after a delay of 1.5 d), accompanied by the temporary formation of an unknown, soluble, organic selenium species. This study shows that a careful process control is a prerequisite for selenium treatment in UASB bioreactors, as disturbances in the operational conditions induce elevated selenium effluent concentrations by alkylation and colloid formation.

Developmental regulation of collagenase-3 mRNA in normal, differentiating osteoblasts through the activator protein-1 and the runt domain binding sites

NASA Technical Reports Server (NTRS)

Winchester, S. K.; Selvamurugan, N.; D'Alonzo, R. C.; Partridge, N. C.

2000-01-01

Collagenase-3 mRNA is initially detectable when osteoblasts cease proliferation, increasing during differentiation and mineralization. We showed that this developmental expression is due to an increase in collagenase-3 gene transcription. Mutation of either the activator protein-1 or the runt domain binding site decreased collagenase-3 promoter activity, demonstrating that these sites are responsible for collagenase-3 gene transcription. The activator protein-1 and runt domain binding sites bind members of the activator protein-1 and core-binding factor family of transcription factors, respectively. We identified core-binding factor a1 binding to the runt domain binding site and JunD in addition to a Fos-related antigen binding to the activator protein-1 site. Overexpression of both c-Fos and c-Jun in osteoblasts or core-binding factor a1 increased collagenase-3 promoter activity. Furthermore, overexpression of c-Fos, c-Jun, and core-binding factor a1 synergistically increased collagenase-3 promoter activity. Mutation of either the activator protein-1 or the runt domain binding site resulted in the inability of c-Fos and c-Jun or core-binding factor a1 to increase collagenase-3 promoter activity, suggesting that there is cooperative interaction between the sites and the proteins. Overexpression of Fra-2 and JunD repressed core-binding factor a1-induced collagenase-3 promoter activity. Our results suggest that members of the activator protein-1 and core-binding factor families, binding to the activator protein-1 and runt domain binding sites are responsible for the developmental regulation of collagenase-3 gene expression in osteoblasts.

Dietary Selenium Levels Affect Selenoprotein Expression and Support the Interferon-γ and IL-6 Immune Response Pathways in Mice

PubMed Central

Tsuji, Petra A.; Carlson, Bradley A.; Anderson, Christine B.; Seifried, Harold E.; Hatfield, Dolph L.; Howard, Michael T.

2015-01-01

Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake. PMID:26258789

Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois: variation within species and relevance to risk communication.

PubMed

Burger, Joanna; Gochfeld, Michael

2013-07-01

There is an emerging consensus that people consuming large amounts of fish with selenium:mercury ratios below 1 are at higher risk from mercury toxicity. As the relative amount of selenium increases compared to mercury, risk may be lowered, but it is unclear how much excess selenium is required. It would be useful if the selenium:mercury ratio was relatively consistent within a species, but this has not been the case in our studies of wild-caught fish. Since most people in developed countries and urban areas obtain their fish and other seafood commercially, we examined selenium:mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago. There was substantial interspecific and intraspecific variation in molar ratios. Across species the selenium:mercury molar ratio decreased with increasing mean mercury levels, but selenium variation also contributed to the ratio. Few samples had selenium:mercury molar ratios below 1, but there was a wide range in ratios, complicating the interpretation for use in risk management and communication. Before ratios can be used in risk management, more information is needed on mercury:selenium interactions and mutual bioavailability, and on the relationship between molar ratios and health outcomes. Further, people who are selenium deficient may be more at risk from mercury toxicity than others. Copyright © 2013 Elsevier Ltd. All rights reserved.

Selenium attenuates apoptosis, inflammation and oxidative stress in the blood and brain of aged rats with scopolamine-induced dementia.

PubMed

Demirci, Kadir; Nazıroğlu, Mustafa; Övey, İshak Suat; Balaban, Hasan

2017-04-01

A potent antioxidant, selenium might modulate dementia-induced progression of brain and blood oxidative and apoptotic injuries. The present study explores whether selenium protects against experimental dementia (scopolamine, SCOP)-induced brain, and blood oxidative stress, apoptosis levels, and cytokine production in rats. Thirty-two rats were equally divided into four groups. The first group was used as an untreated control. The second group was treated with SCOP to induce dementia. The third and fourth groups received 1.5 mg/kg selenium (sodium selenite) and SCOP + selenium, respectively. Dementia was induced in the second and forth groups by intraperitoneal SCOP (1 mg/kg) administration. Brain, plasma, and erythrocyte lipid peroxidation levels as well as plasma TNF-α, interleukin (IL)-1β, and IL-4 levels were high in the SCOP group though they were low in selenium treatments. Selenium and selenium + SCOP treatments increased the lowered glutathione peroxidase activity, reduced glutathione, vitamins A and E concentrations in the brain, erythrocytes and plasma of the SCOP group. Apoptotic value expressions as active caspase-3, procaspase-9, and PARP were also increased by SCOP, while they were decreased by selenium and selenium + SCOP treatments. In conclusion, selenium induced protective effects against experimental dementia-induced brain, and blood oxidative injuries and apoptosis through regulation of cytokine production, vitamin E, glutathione concentrations, and glutathione peroxidase activity.

Selenium and mercury molar ratios in commercial fish from New Jersey and Illinois: Variation within species and relevance to risk communication

PubMed Central

Burger, Joanna; Gochfeld, Michael

2015-01-01

There is an emerging consensus that people consuming large amounts of fish with selenium:mercury ratios below 1 may be at higher risk from mercury toxicity. As the relative amount of selenium increases compared to mercury, risk may be lowered, but it is unclear how much excess selenium is required. It would be useful if the selenium:mercury ratio was relatively consistent within a species, but this has not been the case in our studies of wild-caught fish. Since most people in developed countries and urban areas obtain their fish and other seafood commercially, we examined selenium:mercury molar ratios in commercial fish purchased in stores and fish markets in central New Jersey and Chicago. There was substantial interspecific and intraspecific variation in molar ratios. Across species the selenium:mercury molar ratio decreased with increasing mean mercury levels, but selenium variation also contributed to the ratio. Few samples had selenium:mercury molar ratios below 1, but there was a wide range in ratios, complicating the interpretation for use in risk management and communication. Before ratios can be used in risk management, more information is needed on mercury:selenium interactions and mutual bioavailability, and on the relationship between molar ratios and health outcomes. Further, people who are selenium deficient may be more at risk from mercury toxicity than others. PMID:23541437

Determination of sub-microgram amounts of selenium in geological materials by atomic-absorption spectrophotometry with electrothermal atomisation after solvent extraction

USGS Publications Warehouse

Sanzolone, R.F.; Chao, T.T.

1981-01-01

An atomic-absorption spectrophotometric method with electrothermal atomisation has been developed for the determination of selenium in geological materials. The sample is decomposed with a mixture of nitric, perchloric and hydrofluoric acids and heated with hydrochloric acid to reduce selenium to selenium (IV). Selenium is then extracted into toluene from a hydrochloric acid - hydrobromic acid medium containing iron. A few microlitres of the toluene extract are injected into a carbon rod atomiser, using a nickel solution as a matrix modifier. The limits of determination are 0.2-200 p.p.m. of selenium in a geological sample. For concentrations between 0.05 and 0.2 p.p.m., back-extraction of the selenium into dilute hydrochloric acid is employed before atomisation. Selenium values for reference samples obtained by replicate analysis are in general agreement with those reported by other workers, with relative standard deviations ranging from 4.1 to 8.8%. Recoveries of selenium spiked at two levels were 98-108%. Major and trace elements commonly encountered in geological materials do not interfere. Arsenic has a suppressing effect on the selenium signals, but only when its concentration is greater than 1000 p.p.m. Nitric acid interferes seriously with the extraction of selenium and must be removed by evaporation in the sample-digestion step.

Effects of cytotoxic cis- and trans-diammine monochlorido platinum(II) complexes on selenium-dependent redox enzymes and DNA.

PubMed

Lemmerhirt, Heidi; Behnisch, Steven; Bodtke, Anja; Lillig, Christopher H; Pazderova, Lucia; Kasparkova, Jana; Brabec, Viktor; Bednarski, Patrick J

2018-01-01

Here we present the preparation of 14 pairs of cis- and trans-diammine monochlorido platinum(II) complexes, coordinated to heterocycles (i.e., imidazole, 2-methylimidazole and pyrazole) and linked to various acylhydrazones, which were designed as potential inhibitors of the selenium-dependent enzymes glutathione peroxidase 1 (GPx-1) and thioredoxin reductase 1 (TrxR-1). However, no inhibition of bovine GPx-1 and only weak inhibition of murine TrxR-1 was observed in in vitro assays. Nonetheless, the cis configured diammine monochlorido Pt(II) complexes exhibited cytotoxic and apoptotic properties on various human cancer cell lines, whereas the trans configured complexes generally showed weaker potency with a few exceptions. On the other hand, the trans complexes were generally more likely to lack cross-resistance to cisplatin than the cis analogues. Platinum was found bound to the nuclear DNA of cancer cells treated with representative Pt complexes, suggesting that DNA might be a possible target. Thus, detailed in vitro binding experiments with DNA were conducted. Interactions of the compounds with calf thymus DNA were investigated, including Pt binding kinetics, circular dichroism (CD) spectral changes, changes in DNA melting temperatures, unwinding of supercoiled plasmids and ethidium bromide displacement in DNA. The CD results indicate that the most active cis configured pyrazole-derived complex causes unique structural changes in the DNA compared to the other complexes as well as to those caused by cisplatin, suggesting a denaturation of the DNA structure. This may be important for the antiproliferative activity of this compound in the cancer cells. Copyright © 2017. Published by Elsevier Inc.

Overwinter survival of mallards fed selenium

USGS Publications Warehouse

Heinz, G.H.; Fitzgerald, M.A.

1993-01-01

Adult male mallards (Anas platyrhynchos) were fed diets supplemented with 0, 10, 20, 40, or 80 g/g selenium in the form of selenomethionine. Mortality in each of these treatments was 0, 10, 25, 95, and 100%, respectively, during a 16-week exposure that started in November. After one week of treatment, body weights were significantly depressed by the 20, 40, and 80-ug/g selenium treatments, but not by 10 :g/g selenium. Four weeks after being returned to an untreated diet, the body weight of birds fed 20 ug/g selenium had increased to the point of being statistically inseparable from the weight of controls. Signs of selenium poisoning in the dead included severe emaciation, mottling of the liver, empty gizzard, and the presence of a yellowish fluid around some organs. Concentrations of selenium in blood were related to dietary treatments, but mortality was not clearly related to a threshold concentration of selenium in blood.

Potential reproduction and response of selenium and zinc mineral supplementation on quality of goat samosir semen

NASA Astrophysics Data System (ADS)

Siswoyo, P.; Tafsin, M.; Handarini, R.

2018-02-01

The present study was conducted to investigate the effect of suppllementattion of selenium and zinc on semen quality and growth of samosir goat. The experimental design used latin square design (4x4). The treatment supplementation mineral on multi nutrient block (MNB) composed of without sipplementation (p0), +10ppm selenium (p1), +10ppm zinc (p2), +10ppm selenium and +10ppm zinc (p3). The result showed that supplementation mineral selenium and zinc increased significantly (p<0.05) average daily growth, feed consumtion, and lower feed convertion ratio. Semen quality of goat were supplemented by selenium and zinc influenced motility, viability, volume concentration, and responding hypo osmotic swelling (HOS). Combination supplementation selenium and zinc significanly had higher semen quality than ither treatment. It is concluded that supplementation selenium and zinc improve growth and semen quality of samosir goat.

Organic selenium supplementation increases mercury excretion and decreases oxidative damage in long-term mercury-exposed residents from Wanshan, China.

PubMed

Li, Yu-Feng; Dong, Zeqin; Chen, Chunying; Li, Bai; Gao, Yuxi; Qu, Liya; Wang, Tianchen; Fu, Xin; Zhao, Yuliang; Chai, Zhifang

2012-10-16

Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 μg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.

Crystal Structure of Bfr A from Mycobacterium tuberculosis: Incorporation of Selenomethionine Results in Cleavage and Demetallation of Haem

PubMed Central

Gupta, Vibha; Gupta, Rakesh K.; Khare, Garima; Salunke, Dinakar M.; Tyagi, Anil K.

2009-01-01

Emergence of tuberculosis as a global health threat has necessitated an urgent search for new antitubercular drugs entailing determination of 3-dimensional structures of a large number of mycobacterial proteins for structure-based drug design. The essential requirement of ferritins/bacterioferritins (proteins involved in iron storage and homeostasis) for the survival of several prokaryotic pathogens makes these proteins very attractive targets for structure determination and inhibitor design. Bacterioferritins (Bfrs) differ from ferritins in that they have additional noncovalently bound haem groups. The physiological role of haem in Bfrs is not very clear but studies indicate that the haem group is involved in mediating release of iron from Bfr by facilitating reduction of the iron core. To further enhance our understanding, we have determined the crystal structure of the selenomethionyl analog of bacterioferritin A (SeMet-BfrA) from Mycobacterium tuberculosis (Mtb). Unexpectedly, electron density observed in the crystals of SeMet-BfrA analogous to haem location in bacterioferritins, shows a demetallated and degraded product of haem. This unanticipated observation is a consequence of the altered spatial electronic environment around the axial ligands of haem (in lieu of Met52 modification to SeMet52). Furthermore, the structure of Mtb SeMet-BfrA displays a possible lost protein interaction with haem propionates due to formation of a salt bridge between Arg53-Glu57, which appears to be unique to Mtb BfrA, resulting in slight modulation of haem binding pocket in this organism. The crystal structure of Mtb SeMet-BfrA provides novel leads to physiological function of haem in Bfrs. If validated as a drug target, it may also serve as a scaffold for designing specific inhibitors. In addition, this study provides evidence against the general belief that a selenium derivative of a protein represents its true physiological native structure. PMID:19946376

Identification of AOSC-binding proteins in neurons

NASA Astrophysics Data System (ADS)

Liu, Ming; Nie, Qin; Xin, Xianliang; Geng, Meiyu

2008-11-01

Acidic oligosaccharide sugar chain (AOSC), a D-mannuronic acid oligosaccharide, derived from brown algae polysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer’s Disease (AD) drug candidate. The identification of AOSC-binding protein(s) in neurons is very important for understanding its action mechanism. To determine the binding protein(s) of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 (AP-2) and amyloid precursor protein (APP). These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.

Prediction of Carbohydrate Binding Sites on Protein Surfaces with 3-Dimensional Probability Density Distributions of Interacting Atoms

PubMed Central

Tsai, Keng-Chang; Jian, Jhih-Wei; Yang, Ei-Wen; Hsu, Po-Chiang; Peng, Hung-Pin; Chen, Ching-Tai; Chen, Jun-Bo; Chang, Jeng-Yih; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Non-covalent protein-carbohydrate interactions mediate molecular targeting in many biological processes. Prediction of non-covalent carbohydrate binding sites on protein surfaces not only provides insights into the functions of the query proteins; information on key carbohydrate-binding residues could suggest site-directed mutagenesis experiments, design therapeutics targeting carbohydrate-binding proteins, and provide guidance in engineering protein-carbohydrate interactions. In this work, we show that non-covalent carbohydrate binding sites on protein surfaces can be predicted with relatively high accuracy when the query protein structures are known. The prediction capabilities were based on a novel encoding scheme of the three-dimensional probability density maps describing the distributions of 36 non-covalent interacting atom types around protein surfaces. One machine learning model was trained for each of the 30 protein atom types. The machine learning algorithms predicted tentative carbohydrate binding sites on query proteins by recognizing the characteristic interacting atom distribution patterns specific for carbohydrate binding sites from known protein structures. The prediction results for all protein atom types were integrated into surface patches as tentative carbohydrate binding sites based on normalized prediction confidence level. The prediction capabilities of the predictors were benchmarked by a 10-fold cross validation on 497 non-redundant proteins with known carbohydrate binding sites. The predictors were further tested on an independent test set with 108 proteins. The residue-based Matthews correlation coefficient (MCC) for the independent test was 0.45, with prediction precision and sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound carbohydrate-binding protein structures for which the structures were determined in the absence of the carbohydrate ligands were predicted with the trained predictors. The overall prediction MCC was 0.49. Independent tests on anti-carbohydrate antibodies showed that the carbohydrate antigen binding sites were predicted with comparable accuracy. These results demonstrate that the predictors are among the best in carbohydrate binding site predictions to date. PMID:22848404

Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer

DTIC Science & Technology

2010-05-01

TITLE: Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer PRINCIPAL INVESTIGATOR...May 2009 - 30 Apr 2010 4. TITLE AND SUBTITLE Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer...telomerase as a potential target of AR signaling suppression by selenium . We found that combination of selenium and bicalutamide produced a robust down

Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial

PubMed Central

Alexander, Jan; Aaseth, Jan

2016-01-01

Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; <65 μg/L, 65–85 μg/L, and >85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of >85 μg/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 μg/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations <65 μg/L in comparison with those having a selenium concentration >85 μg/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, ≤85 at inclusion. In those with serum selenium>85 μg/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted. Trial Registration Clinicaltrials.gov NCT01443780 PMID:27367855

Selenium concentrations in the razorback sucker (Xyrauchen texanus): Substitution of non-lethal muscle plugs for muscle tissue in contaminant assessment

USGS Publications Warehouse

Waddell, B.; May, T.

1995-01-01

A single muscle plug was collected from each of 25 live razorback suckers inhabiting the Colorado River basin and analyzed for selenium by instrumental neutron activation. Eight fish from Ashley Creek and three from Razorback Bar exhibited selenium concentrations exceeding 8 μg/g, a level associated with reproductive failure in fish. Concentrations of selenium in eggs and milt were significantly correlated with selenium concentrations in muscle plugs and together indicate a possible explanation for the decline of this species in the Colorado River basin. Muscle plugs (<50mg) and muscle tissue (20 g) were collected from dorsal, anterior, and posterior areas of common carp, flannelmouth sucker, and an archived razorback sucker and analyzed for selenium. Concentrations of selenium in muscle plugs were significantly correlated with selenium concentrations in muscle tissue from the same location and fish (r=0.97). Coefficients of variation for selenium concentrations in each fish were <6.5% for muscle tissue, but ranged from 1.5 to 32.4% for muscle plugs. Increased variation in muscle plugs was attributed to lower selenium concentrations found in the anterior muscle plugs of flannelmouth suckers. Mean selenium concentrations in muscle plugs and tissue from dorsal and posterior areas and muscle tissue from the anterior area were not significantly different. The non-lethal collection of a muscle plug from dorsal and posterior areas of the razorback sucker and other fish species may provide an accurate assessment of selenium concentrations that exist in adjacent muscle tissue.

Assessment of selenium nutritional status of school-age children from rural areas of China in 2002 and 2012.

PubMed

Liu, X; Piao, J; Li, M; Zhang, Y; Yun, C; Yang, C; Yang, X

2016-03-01

To assess the selenium nutritional status of 3458 school-age children recruited from rural areas using the China Nutrition and Health Survey 2002 and 2012 (CNHS 2002 and CNHS 2012). The serum selenium concentration was determined by high-resolution inductively coupled plasma mass spectrometry. The prevalence of dietary selenium intake insufficiency was calculated according to the formula suggested by and the estimated average requirements of the new Chinese Dietary Reference Intakes. The percentage of low selenium was based on the cutoff values with a serum selenium concentration below the threshold limit of clinical importance in coronary and cardiovascular diseases (<45 μg/l) and in abnormal physiological functions (<60 μg/l). The overall median serum selenium concentration was 64.3 μg/l in the CNHS 2002 and 74.2 μg/l in the CNHS 2012. The median calculated dietary selenium intake was 26.7 μg/day in the CNHS 2002 and 33.2 μg/day in the CNHS 2012 together with a 61.1% and 52.8% dietary selenium intake insufficiency in the CNHS 2002 and in the CNHS 2012. In addition, the percentages of low selenium (<45 μg/l and <60 μg/l) were 25.1 and 43.8% in the CNHS 2002 but 9.4 and 25.6% in the CHNS 2012. The selenium nutritional status of school-age children was significantly improved in the CNHS 2012 versus the CNHS 2002. However, the health risk for selenium malnutrition in school-age children remains a potential problem affecting children's health.

Exploring DNA-binding Proteins with In Vivo Chemical Cross-linking and Mass Spectrometry

PubMed Central

Qiu, Haibo; Wang, Yinsheng

2009-01-01

DNA-binding proteins are very important constituents of proteomes of all species and play crucial roles in transcription, DNA replication, recombination, repair and other activities associated with DNA. Although a number of DNA-binding proteins have been identified, many proteins involved in gene regulation and DNA repair are likely still unknown because of their dynamic and/or weak interactions with DNA. In this report, we described an approach for the comprehensive identification of DNA-binding proteins with in vivo formaldehyde cross-linking and LC-MS/MS. DNA-binding proteins could be purified via the isolation of DNA-protein complexes and released from the complexes by reversing the cross-linking. By using this method, we were able to identify more than one hundred DNA-binding proteins, such as proteins involved in transcription, gene regulation, DNA replication and repair, and a large number of proteins which are potentially associated with DNA and DNA-binding proteins. This method should be generally applicable to the investigation of other nucleic acid-binding proteins, and hold great potential in the comprehensive study of gene regulation, DNA damage response and repair, as well as many other critical biological processes at proteomic level. PMID:19714816

Adrenocortical nuclear progesterone-binding protein: Identification by photoaffinity labeling and evidence for deoxyribonucleic acid binding and stimulation by adrenocorticotropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demura, T.; Driscoll, W.J.; Lee, Y.C.

1991-01-01

Nuclei of the guinea pig adrenal cortex contain a protein that specifically binds progesterone and that, biochemically, is clearly distinct from the classical progesterone receptor. The adrenocortical nuclear progesterone-binding protein has now been purified more than 2000-fold by steroid-affinity chromatography with a 75% yield. The purified protein preparation demonstrated three major bands on sodium dodecyl sulfate-polyacrylamide gel of 79K, 74K, and 50K. To determine which of the three might represent the progesterone-binding protein, steroid photoaffinity labeling was performed which resulted in the specific and exclusive labeling of a 50K band. Thus, the adrenocortical nuclear progesterone-binding protein appears to be distinctmore » from the classical progesterone receptor not only biochemically, but also on the basis of molecular size. To test whether the adrenocortical nuclear progesterone-binding protein can be hormonally stimulated, guinea pigs were treated with ACTH. The chronic administration of ACTH caused a 4- to 6-fold increase in the specific progesterone binding capacity without a change in the binding affinity. There appeared to be no significant difference in nuclear progesterone binding between the zona fasciculata and zona reticularis. This finding suggests a mediating role for the progesterone-binding protein in ACTH action. In addition, the nuclear progesterone-binding protein bound to nonspecific DNA sequences, further suggesting a possible transcriptional regulatory role.« less

Nano-selenium and its nanomedicine applications: a critical review.

PubMed

Hosnedlova, Bozena; Kepinska, Marta; Skalickova, Sylvie; Fernandez, Carlos; Ruttkay-Nedecky, Branislav; Peng, Qiuming; Baron, Mojmir; Melcova, Magdalena; Opatrilova, Radka; Zidkova, Jarmila; Bjørklund, Geir; Sochor, Jiri; Kizek, Rene

2018-01-01

Traditional supplements of selenium generally have a low degree of absorption and increased toxicity. Therefore, it is imperative to develop innovative systems as transporters of selenium compounds, which would raise the bioavailability of this element and allow its controlled release in the organism. Nanoscale selenium has attracted a great interest as a food additive especially in individuals with selenium deficiency, but also as a therapeutic agent without significant side effects in medicine. This review is focused on the incorporation of nanotechnological applications, in particular exploring the possibilities of a more effective way of administration, especially in selenium-deficient organisms. In addition, this review summarizes the survey of knowledge on selenium nanoparticles, their biological effects in the organism, advantages, absorption mechanisms, and nanotechnological applications for peroral administration.

Plasma Selenium Concentrations Are Sufficient and Associated with Protease Inhibitor Use in Treated HIV-Infected Adults123

PubMed Central

Hileman, Corrilynn O; Dirajlal-Fargo, Sahera; Lam, Suet Kam; Kumar, Jessica; Lacher, Craig; Combs, Gerald F; McComsey, Grace A

2015-01-01

Background: Selenium is an essential constituent of selenoproteins, which play a substantial role in antioxidant defense and inflammatory cascades. Selenium deficiency is associated with disease states characterized by inflammation, including cardiovascular disease (CVD). Although HIV infection has been associated with low selenium, the role of selenium status in HIV-related CVD is unclear. Objectives: We sought to assess associations between plasma selenium and markers of inflammation, immune activation, and subclinical vascular disease in HIV-infected adults on contemporary antiretroviral therapy (ART) and to determine if statin therapy modifies selenium status. Methods: In the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN trial, HIV-infected adults on stable ART were randomly assigned 1:1 to rosuvastatin or placebo. Plasma selenium concentrations were determined at entry, week 24, and week 48. Spearman correlation and linear regression analyses were used to assess relations between baseline selenium, HIV-related factors and markers of inflammation, immune activation, and subclinical vascular disease. Changes in selenium over 24 and 48 wk were compared between groups. Results: One hundred forty-seven HIV-infected adults were included. All participants were on ART. Median current CD4+ count was 613, and 76% had HIV-1 RNA ≤48 copies/mL (range: <20–600). Median plasma selenium concentration was 122 μg/L (range: 62–200). At baseline, higher selenium was associated with protease inhibitor (PI) use, lower body mass index, and a higher proportion of activated CD8+ T cells (CD8+CD38+human leukocyte antigen-DR+), but not markers of inflammation or subclinical vascular disease. Over 48 wk, selenium concentrations increased in the statin group (P < 0.01 within group), but the change did not differ between groups (+13.1 vs. +5.3 μg/L; P = 0.14 between groups). Conclusions: Plasma selenium concentrations were within the normal range for the background population and were not associated with subclinical vascular disease in HIV-infected adults on contemporary ART. The association between current PI use and higher selenium may have implications for ART allocation, especially in resource-limited countries. Also, it appears that statin therapy may increase selenium concentrations; however, larger studies are necessary to confirm this finding. This trial was registered at clinicaltrials.gov as NCT01218802. PMID:26269240

Effects of Dietary Selenium and Vitamin E on Growth Performance, Meat Yield, and Selenium Content and Lipid Oxidation of Breast Meat of Broilers Reared Under Heat Stress.

PubMed

Habibian, Mahmood; Ghazi, Shahab; Moeini, Mohammad Mehdi

2016-01-01

This study was conducted using 360 broiler chickens to evaluate the effects of dietary vitamin E (0, 125, and 250 mg/kg), selenium (0, 0.5, and 1 mg/kg), or their different combinations on performance, meat yield, and selenium content and lipid oxidation of breast meat of broilers raised under either a thermoneutral (TN, 24 °C constant) or heat stress (HS, 24 to 37 °C cycling) condition. There was a reduction (P < 0.05) in body weight and feed intake and an increase (P < 0.05) in feed conversion ratio when broilers exposed to HS. In the overall period of the study (1 to 49 days), growth performance of TN broilers was not affected (P < 0.05) by vitamin E and selenium supplementation. However, under HS condition, broilers receiving 250 mg/kg vitamin E and 0.5 mg/kg selenium consumed more (P < 0.05) feed than that of broilers receiving 250 mg/kg vitamin E alone, but similar (P > 0.05) to that of broilers receiving 250 mg/kg vitamin E and 1 mg/kg selenium. The malondialdehyde (MDA) content of the breast meat was increased (P < 0.05), but its selenium content was decreased (P < 0.05) by exposure to HS. The breast meat selenium content was increased (P < 0.05) by selenium supplementation. The breast meat selenium content was decreased (P < 0.05) by supplementation of 250 mg/kg vitamin E to diet of TN birds. However, the breast meat selenium content was increased (P < 0.05) by supplementation of vitamin E under HS condition. The breast meat MDA content was not affected (P > 0.05) by dietary treatments under TN condition. However, the breast meat MDA content was decreased (P < 0.05) by both vitamin E and selenium supplementation under HS condition, and the lowest MDA content was observed in the breast meat of broilers receiving combination of 125 mg/kg vitamin E and 1 mg/kg selenium. The results showed that supplementation of selenium and vitamin E was capable of increasing the selenium content of the breast meat and could improve the lipid oxidation of the breast meat when broilers reared under HS condition.

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

PubMed

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry.

PubMed

Vinceti, Marco; Maraldi, Tullia; Bergomi, Margherita; Malagoli, Carlotta

2009-01-01

The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed.

Methylselenol, a selenium metabolite, modulates p53 pathway and inhibits the growth of colon cancer xenografts in Balb/c mice.

PubMed

Zeng, Huawei; Cheng, Wen-Hsing; Johnson, Luann K

2013-05-01

It is has been hypothesized that methylselenol is a critical selenium metabolite for anticancer activity in vivo. In this study, we used a protein array which contained 112 different antibodies known to be involved in the p53 pathway to investigate the molecular targets of methylselenol in human HCT116 colon cancer cells. The array analysis indicated that methylselenol exposure changed the expression of 11 protein targets related to the regulation of cell cycle and apoptosis. Subsequently, we confirmed these proteins with the Western blotting approach, and found that methylselenol increased the expression of GADD 153 and p21 but reduced the level of c-Myc, E2F1 and Phos p38 MAP kinase. Similar to our previous report on human HCT116 colon cancer cells, methylselenol also inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase in mouse colon cancer MC26 cells. When the MC26 cells were transplanted to their immune-competent Balb/c mice, methylselenol-treated MC26 cells had significantly less tumor growth potential than that of untreated MC26 cells. Taken together, our data suggest that methylselenol modulates the expression of key genes related to cell cycle and apoptosis and inhibits colon cancer cell proliferation and tumor growth. Copyright © 2013. Published by Elsevier Inc.

Protective Effect of Selenium on Aflatoxin B1-Induced Testicular Toxicity in Mice.

PubMed

Cao, Zheng; Shao, Bing; Xu, Feibo; Liu, Yunfeng; Li, Yanfei; Zhu, Yanzhu

2017-12-01

Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.

Specificity in substrate binding by protein folding catalysts: tyrosine and tryptophan residues are the recognition motifs for the binding of peptides to the pancreas-specific protein disulfide isomerase PDIp.

PubMed Central

Ruddock, L. W.; Freedman, R. B.; Klappa, P.

2000-01-01

Using a cross-linking approach, we recently demonstrated that radiolabeled peptides or misfolded proteins specifically interact in vitro with two luminal proteins in crude extracts from pancreas microsomes. The proteins were the folding catalysts protein disulfide isomerase (PDI) and PDIp, a glycosylated, PDI-related protein, expressed exclusively in the pancreas. In this study, we explore the specificity of these proteins in binding peptides and related ligands and show that tyrosine and tryptophan residues in peptides are the recognition motifs for their binding by PDIp. This peptide-binding specificity may reflect the selectivity of PDIp in binding regions of unfolded polypeptide during catalysis of protein folding. PMID:10794419

Dominant Alcohol-Protein Interaction via Hydration-Enabled Enthalpy-Driven Binding Mechanism

PubMed Central

Chong, Yuan; Kleinhammes, Alfred; Tang, Pei; Xu, Yan; Wu, Yue

2015-01-01

Water plays an important role in weak associations of small drug molecules with proteins. Intense focus has been on binding-induced structural changes in the water network surrounding protein binding sites, especially their contributions to binding thermodynamics. However, water is also tightly coupled to protein conformations and dynamics, and so far little is known about the influence of water-protein interactions on ligand binding. Alcohols are a type of low-affinity drugs, and it remains unclear how water affects alcohol-protein interactions. Here, we present alcohol adsorption isotherms under controlled protein hydration using in-situ NMR detection. As functions of hydration level, Gibbs free energy, enthalpy, and entropy of binding were determined from the temperature dependence of isotherms. Two types of alcohol binding were found. The dominant type is low-affinity nonspecific binding, which is strongly dependent on temperature and the level of hydration. At low hydration levels, this nonspecific binding only occurs above a threshold of alcohol vapor pressure. An increased hydration level reduces this threshold, with it finally disappearing at a hydration level of h~0.2 (g water/g protein), gradually shifting alcohol binding from an entropy-driven to an enthalpy-driven process. Water at charged and polar groups on the protein surface was found to be particularly important in enabling this binding. Although further increase in hydration has smaller effects on the changes of binding enthalpy and entropy, it results in significant negative change in Gibbs free energy due to unmatched enthalpy-entropy compensation. These results show the crucial role of water-protein interplay in alcohol binding. PMID:25856773

Forecasting Selenium Discharges to the San Francisco Bay-Delta Estuary: Ecological Effects of A Proposed San Luis Drain Extension

USGS Publications Warehouse

Presser, Theresa S.; Luoma, Samuel N.

2006-01-01

Selenium discharges to the San Francisco Bay-Delta Estuary (Bay-Delta) could change significantly if federal and state agencies (1) approve an extension of the San Luis Drain to convey agricultural drainage from the western San Joaquin Valley to the North Bay (Suisun Bay, Carquinez Strait, and San Pablo Bay); (2) allow changes in flow patterns of the lower San Joaquin River and Bay-Delta while using an existing portion of the San Luis Drain to convey agricultural drainage to a tributary of the San Joaquin River; or (3) revise selenium criteria for the protection of aquatic life or issue criteria for the protection of wildlife. Understanding the biotransfer of selenium is essential to evaluating effects of selenium on Bay-Delta ecosystems. Confusion about selenium threats to fish and wildlife stem from (1) monitoring programs that do not address specific protocols necessary for an element that bioaccumulates; and (2) failure to consider the full complexity of the processes that result in selenium toxicity. Past studies show that predators are more at risk from selenium contamination than their prey, making it difficult to use traditional methods to predict risk from environmental concentrations alone. This report presents an approach to conceptualize and model the fate and effects of selenium under various load scenarios from the San Joaquin Valley. For each potential load, progressive forecasts show resulting (1) water-column concentration; (2) speciation; (3) transformation to particulate form; (4) particulate concentration; (5) bioaccumulation by invertebrates; (6) trophic transfer to predators; and (7) effects on those predators. Enough is known to establish a first-order understanding of relevant conditions, biological response, and ecological risks should selenium be discharged directly into the North Bay through a conveyance such as a proposed extension of the San Luis Drain. The approach presented here, the Bay-Delta selenium model, determines the mass, fate, and effects of selenium released to the Bay-Delta through use of (1) historical land-use, drainage, alluvial-fill, and runoff databases; (2) existing knowledge concerning biogeochemical reactions and physiological parameters of selenium (e.g., speciation, partitioning between dissolved and particulate forms, and bivalve assimilation efficiency); and (3) site-specific data mainly from 1986 to 1996 for clams and bottom-feeding fish and birds. Selenium load scenarios consider effluents from North Bay oil refineries and discharges of agricultural drainage from the San Joaquin Valley to enable calculation of (a) a composite freshwater endmember selenium concentration at the head of the estuary; and (b) a selenium concentration at a selected seawater location (Carquinez Strait) as a foundation for modeling. Analysis of selenium effects also takes into account the mode of conveyance for agricultural drainage (i.e., the San Luis Drain or San Joaquin River); and flows of the Sacramento River and San Joaquin River on a seasonal or monthly basis. Load scenarios for San Joaquin Valley mirror predictions made since 1955 of a worsening salt (and by inference, selenium) build-up exacerbated by an arid climate and massive irrigation. The reservoir of selenium in the San Joaquin Valley is sufficient to provide loading at an annual rate of approximately 42,500 pounds of selenium to a Bay-Delta disposal point for 63 to 304 years at the lower range of projections presented here, even if influx of selenium from the California Coast Ranges could be curtailed. Disposal of wastewaters on an annual basis outside of the San Joaquin Valley may slow the degradation of valley resources, but drainage alone cannot alleviate the salt and selenium build-up in the San Joaquin Valley, at least within a century. Load scenarios also show the different proportions of selenium loading to the Bay-Delta. Oil refinery loads from 1986 to 1992 ranged from 8.5 to 20 pounds of selenium per day;

Detailed study of selenium and other constituents in water, bottom sediment, soil, alfalfa, and biota associated with irrigation drainage in the Uncompahgre Project area and in the Grand Valley, west-central Colorado, 1991-93

USGS Publications Warehouse

Butler, D.L.; Wright, W.G.; Stewart, K.C.; Osmundson, B.C.; Krueger, R.P.; Crabtree, D.W.

1996-01-01

In 1985, the U.S. Department of the Interior began a program to study the effects of irrigation drainage in the Western United States. These studies were done to determine whether irrigation drainage was causing problems related to human health, water quality, and fish and wildlife resources. Results of a study in 1991-93 of irrigation drainage associated with the Uncompahgre Project area, located in the lower Gunnison River Basin, and of the Grand Valley, located along the Colorado River, are described in this report. The focus of the report is on the sources, distribution, movement, and fate of selenium in the hydrologic and biological systems and the effects on biota. Generally, other trace- constituent concentrations in water and biota were not elevated or were not at levels of concern. Soils in the Uncompahgre Project area that primarily were derived from Mancos Shale contained the highest concentrations of total and watrer-extractable selenium. Only 5 of 128\\x11alfalfa samples had selenium concentrations that exceeded a recommended dietary limit for livestock. Selenium data for soil and alfalfa indicate that irrigation might be mobilizing and redistributing selenium in the Uncompahgre Project area. Distribution of dissolved selenium in ground water is affected by the aqueous geochemical environment of the shallow ground- water system. Selenium concentrations were as high as 1,300\\x11micrograms per liter in water from shallow wells. The highest concentrations of dissolved selenium were in water from wells completed in alluvium overlying the Mancos Shale of Cretaceous age; selenium concentrations were lower in water from wells completed in Mancos Shale residuum. Selenium in the study area could be mobilized by oxidation of reduced selenium, desorption from aquifer sediments, ion exchange, and dissolution. Infiltration of irrigation water and, perhaps nitrate, provide oxidizing conditions for mobilization of selenium from alluvium and shale residuum and for transport to streams and irrigation drains that are tributary to the Gunnison, Uncompahgre, and Colorado Rivers. Selenium concentrations in about 64\\x11percent of water samples collected from the lower Gunnison River and about 50 percent of samples from the Colorado River near the Colorado-Utah State line exceeded the U.S.\\x11Environmental Protection Agency criterion of 5\\x11micrograms per liter for protection of aquatic life. Almost all selenium concentrations in samples collected during the nonirrigation season from Mancos Shale areas exceeded the aquatic-life criterion. The maximum selenium concentrations in surface-water samples were 600\\x11micrograms per liter in the Uncompahgre Project area and 380\\x11micrograms per liter in the Grand Valley. Irrigation drainage from the Uncompahgre Project and the Grand Valley might account for as much as 75 percent of the selenium load in the Colorado River near the Colorado-Utah State line. The primary source areas of selenium were the eastern side of the Uncompahgre Project and the western one-half of the Grand Valley, where there is extensive irrigation on soils derived from Mancos Shale. The largest mean selenium loads from tributary drainages were 14.0 pounds per day from Loutsenhizer Arroyo in the Uncompahgre Project and 12.8 pounds per day from Reed Wash in the Grand Valley. Positive correlations between selenium loads and dissolved-solids loads could indicate that salinity-control projects designed to decrease dissolved-solids loads also could decrease selenium loads from the irrigated areas. Selenium concentrations in irrigation drainage in the Grand Valley were much higher than concentrations predicted by simple evaporative concentration of irrigation source water. Selenium probably is removed from pond water by chemical and biological processes and incorporated into bottom sediment. The maximum selenium concentration in bottom sediment was 47 micrograms per gram from a pond on the eastern side of the

Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence.

PubMed

Gustafsson, Mattias C U; Lannergård, Jonas; Nilsson, O Rickard; Kristensen, Bodil M; Olsen, John E; Harris, Claire L; Ufret-Vincenty, Rafael L; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar

2013-01-01

Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.

Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence

PubMed Central

Kristensen, Bodil M.; Olsen, John E.; Harris, Claire L.; Ufret-Vincenty, Rafael L.; Stålhammar-Carlemalm, Margaretha; Lindahl, Gunnar

2013-01-01

Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems. PMID:23637608

[Glutamate-binding membrane proteins from human platelets].

PubMed

Gurevich, V S; Popov, Iu G; Gorodinskiĭ, A I; Dambinova, S A

1991-09-01

Solubilization of the total membrane fraction of human platelets in a 2% solution of sodium deoxycholate and subsequent affinity chromatography on glutamate agarose resulted in two protein fractions possessing a glutamate-binding activity. As can be evidenced from radioligand binding data, the first fraction contains two types of binding sites (Kd1 = 1 microM, Bmax 1 = 100 pmol/mg of protein; Kd2 = 9.3 microMm Bmax2 = 395 pmol/mg of protein). The second fraction has only one type of binding sites (Kd = 1 microM, Bmax = = 110 pmol/mg of protein). SDS-PAAG electrophoresis revealed the presence in the first fraction of proteins with Mr of 14, 24, 56 and 155 kDa, whereas the second fraction was found to contain 14, 46, 71 and 155 kDa proteins. Solid phase immunoenzymatic analysis using poly- and monoclonal specific antibodies against mammalian brain glutamate-binding proteins revealed a marked immunochemical similarity of the isolated protein fractions with human brain synaptic membrane glutamate-binding proteins.

Selenium

USGS Publications Warehouse

Franson, J.C.

1999-01-01

Selenium is a naturally occurring element that is present in some soils. Unlike mercury and lead, which also are natural environmental components, selenium is an essential nutrient in living systems. The amount of dietary selenium required by animals depends upon many factors, including the availability of certain other metals such as zinc and copper, as well as vitamin E and other nutrients. Muscle damage results if dietary selenium is deficient, but dietary excess can be toxic.

Selenium deficiency in cattle associated with Heinz bodies and anemia.

PubMed

Morris, J G; Cripe, W S; Chapman, H L; Walker, D F; Armstrong, J B; Alexander, J D; Miranda, R; Sanchez, A; Sanchez, B; Blair-West, J R

1984-02-03

Cattle grazing St. Augustine grass growing on peaty muck soils in the Florida Everglades developed anemia associated with the presence of Heinz bodies and suboptimal concentrations of selenium in blood. Selenium supplementation corrected the anemia, prevented Heinz body formation, increased the body weight of cows and calves, and elevated blood selenium. This may be the first recorded example of widespread anemia in a population due to selenium deficiency.

Avoidance of selenium-treated food by mallards

USGS Publications Warehouse

Heinz, G.H.; Sanderson, C.J.

1990-01-01

Adult, male mallards (Anas platyrhynchos) were given a choice between a control diet and a diet containing 5, 10 or 20 ppm selenium as selenomethionine dissolved in water and mixed into the diet. At 10 and 20 ppm, selenium-treated diets were avoided. Avoidance appeared to be caused by a conditioned response, probably to illness caused by the selenium and not to an aversion to the taste of the selenium.

Selenium and selenocysteine: roles in cancer, health and development

PubMed Central

Hatfield, Dolph L.; Tsuji, Petra A.; Carlson, Bradley A.; Gladyshev, Vadim N.

2014-01-01

The many biological and biomedical effects of selenium are relatively unknown outside the selenium field. This fascinating element, initially described as a toxin, was subsequently shown to be essential for health and development. By the mid 1990s, selenium emerged as one of the most promising cancer chemopreventive agents, but subsequent human clinical trials yielded contradictory results. However, basic research on selenium continued to move at a rapid pace elucidating its many roles in health, development, and cancer prevention and promotion. Dietary selenium acts principally through selenoproteins, most of which are oxidoreductases involved in diverse cellular functions. PMID:24485058

Investigation of electrical noise in selenium-immersed thermistor bolometers

NASA Technical Reports Server (NTRS)

Tarpley, J. L.; Sarmiento, P. D.

1980-01-01

The selenium immersed, thermistor bolometer, IR detector failed due to spurious and escalating electrical noise outburst as a function of time at elevated temperatures during routine ground based testing in a space simulated environment. Spectrographic analysis of failed bolometers revealed selenium pure zones in the insulating selenium arsenic (Se-As) glass film which surrounds the active sintered Mn, Ni, Co oxide flake. The selenium pure film was identified as a potentially serious failure mechanism. Significant changes were instituted in the manufacturing techniques along with more stringent process controls which eliminated the selenium pure film and successfully produced 22study bolometers.

Hazard assessment of selenium to endangered razorback suckers (Xyrauchen texanus)

USGS Publications Warehouse

Hamilton, S.J.; Holley, K.M.; Buhl, K.J.

2002-01-01

A hazard assessment was conducted based on information derived from two reproduction studies conducted with endangered razorback suckers (Xyrauchen texanus) at three sites near Grand Junction, CO, USA. Selenium contamination of the upper and lower Colorado River basin has been documented in water, sediment, and biota in studies by US Department of the Interior agencies and academia. Concern has been raised that this selenium contamination may be adversely affecting endangered fish in the upper Colorado River basin. The reproduction studies with razorback suckers revealed that adults readily accumulated selenium in various tissues including eggs, and that 4.6 μg/g of selenium in food organisms caused increased mortality of larvae. The selenium hazard assessment protocol resulted in a moderate hazard at the Horsethief site and high hazards at the Adobe Creek and North Pond sites. The selenium hazard assessment was considered conservative because an on-site toxicity test with razorback sucker larvae using 4.6 μg/g selenium in zooplankton caused nearly complete mortality, in spite of the moderate hazard at Horsethief. Using the margin of uncertainty ratio also suggested a high hazard for effects on razorback suckers from selenium exposure. Both assessment approaches suggested that selenium in the upper Colorado River basin adversely affects the reproductive success of razorback suckers.

Effects of selenium on mallard duck reproduction and immune function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whiteley, P.L.; Yuill, T.M.; Fairbrother, A.

Selenium from irrigation drain water and coal-fired power stations is a significant environmental contaminant in some regions of the USA. The objectives were to examine whether selenium-exposed waterfowl had altered immune function, disease resistance, or reproduction. Pairs of adult mallards were exposed for 95-99 days on streams with sodium selenite-treated water at 10 and 30 ppb, or on untreated streams. Selenium biomagnified through the food chain to the ducks. Disease resistance was decreased in ducklings hatched on the streams and challenged with duck hepatitis virus 1 (DHV1) when 15-days old. Liver selenium concentrations for these ducklings on the 10 andmore » 30 ppb streams was 3.6 and 7.6 ppm dry weight, respectively. Mortality of ducklings purchased when 7-days old, exposed to selenium for 14 days, and challenged when 22-days old was not affected. However, their selenium exposure was lower (liver selenium 4.1 ppm dry weight for the 30 ppb stream). Five parameters of immune function were measured in adult ducks. Phagocytosis of killed Pasteurella multocida by blood heterophils and monocytes, and blood monocyte concentrations were higher in adult males following 84 days exposure to 30 ppb selenium. Their liver selenium concentrations were 11.1 ppm dry weight after 95-99 days exposure.« less

Hazard assessment of selenium to endangered razorback suckers (Xyrauchen texanus).

PubMed

Hamilton, Steven J; Holley, Kathleen M; Buhl, Kevin J

2002-05-27

A hazard assessment was conducted based on information derived from two reproduction studies conducted with endangered razorback suckers (Xyrauchen texanus) at three sites near Grand Junction, CO, USA. Selenium contamination of the upper and lower Colorado River basin has been documented in water, sediment, and biota in studies by US Department of the Interior agencies and academia. Concern has been raised that this selenium contamination may be adversely affecting endangered fish in the upper Colorado River basin. The reproduction studies with razorback suckers revealed that adults readily accumulated selenium in various tissues including eggs, and that 4.6 microg/g of selenium in food organisms caused increased mortality of larvae. The selenium hazard assessment protocol resulted in a moderate hazard at the Horsethief site and high hazards at the Adobe Creek and North Pond sites. The selenium hazard assessment was considered conservative because an on-site toxicity test with razorback sucker larvae using 4.6 microg/g selenium in zooplankton caused nearly complete mortality, in spite of the moderate hazard at Horsethief. Using the margin of uncertainty ratio also suggested a high hazard for effects on razorback suckers from selenium exposure. Both assessment approaches suggested that selenium in the upper Colorado River basin adversely affects the reproductive success of razorback suckers.

Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna.

PubMed

Yamashita, Yumiko; Yamashita, Michiaki

2010-06-11

A novel selenium-containing compound having a selenium atom in the imidazole ring, 2-selenyl-N(alpha),N(alpha),N(alpha)-trimethyl-L-histidine, 3-(2-hydroseleno-1H-imidazol-5-yl)-2-(trimethylammonio)propanoate, was identified from the blood and other tissues of the bluefin tuna, Thunnus orientalis. The selenium-containing compound was purified from the tuna blood in several chromatographic steps. High resolution mass spectrometry and nuclear magnetic resonance spectroscopy showed that the exact mass of the [M+H](+) ion of the compound was 533.0562 and the molecular formula was C(18)H(29)N(6)O(4)Se(2). Its gross structure was assigned as the oxidized dimeric form of an ergothioneine selenium analog in which the sulfur of ergothioneine is replaced by selenium. Therefore, we named this novel selenium-containing compound "selenoneine." By speciation analysis of organic selenium compounds using liquid chromatography inductively coupled plasma mass spectrometry, selenoneine was found widely distributed in various tissues of the tuna, with the highest concentration in blood; mackerel blood contained similar levels. Selenoneine was measurable at 2-4 orders of magnitude lower concentration in a limited set of tissues from squid, tilapia, pig, and chicken. Quantitatively, selenoneine is the predominant form of organic selenium in tuna tissues.

Hyperdiversity of Genes Encoding Integral Light-Harvesting Proteins in the Dinoflagellate Symbiodinium sp

PubMed Central

Boldt, Lynda; Yellowlees, David; Leggat, William

2012-01-01

The superfamily of light-harvesting complex (LHC) proteins is comprised of proteins with diverse functions in light-harvesting and photoprotection. LHC proteins bind chlorophyll (Chl) and carotenoids and include a family of LHCs that bind Chl a and c. Dinophytes (dinoflagellates) are predominantly Chl c binding algal taxa, bind peridinin or fucoxanthin as the primary carotenoid, and can possess a number of LHC subfamilies. Here we report 11 LHC sequences for the chlorophyll a-chlorophyll c 2-peridinin protein complex (acpPC) subfamily isolated from Symbiodinium sp. C3, an ecologically important peridinin binding dinoflagellate taxa. Phylogenetic analysis of these proteins suggests the acpPC subfamily forms at least three clades within the Chl a/c binding LHC family; Clade 1 clusters with rhodophyte, cryptophyte and peridinin binding dinoflagellate sequences, Clade 2 with peridinin binding dinoflagellate sequences only and Clades 3 with heterokontophytes, fucoxanthin and peridinin binding dinoflagellate sequences. PMID:23112815

Protein Binding: Do We Ever Learn?▿

PubMed Central

Zeitlinger, Markus A.; Derendorf, Hartmut; Mouton, Johan W.; Cars, Otto; Craig, William A.; Andes, David; Theuretzbacher, Ursula

2011-01-01

Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agents in vitro. This might explain the somewhat contradictory results obtained from different studies. Simple in vitro models which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Within in vitro test systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibiotics in vitro become even more urgent. In addition, the quantitative relationship between the effects of protein binding in vitro and in vivo needs to be established, since the physiological conditions differ. General recommendations for testing the impact of protein binding in vitro are suggested. PMID:21537013

Selenium-75-labeled sucralfate: comparison with other radiolabels and initial clinical studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knight, L.C.; Maurer, A.H.; Kollmann, M.

1988-01-01

Sucralfate was synthesized to include a /sup 75/Se label, then compared with /sup 111/In-sucralfate and /sup 99m/Tc-Human serum albumin (HSA)-sucralfate in vitro and in an animal ulcer model. The /sup 75/Se label was the only one of the three that was stable in both human gastric juice and simulated intestinal fluid in vitro. In rats with gastric ulcers, ulcer:nonulcer ratios of bound radioactivity averaged 15.4, 6.3, and 5.6 for /sup 75/Se, /sup 111/In, and /sup 99m/Tc-HSA labels, respectively. Biodistribution studies of /sup 75/Se-sucralfate indicated that little is absorbed from the gastrointestinal tract, and the distribution is similar to that ofmore » /sup 14/C-sucralfate. Selective binding of /sup 75/Se sucralfate was successfully imaged in patients with esophagitis (esophageal mean T1/2 binding = 65 +/- 32 min), gastritis (gastric mean T 1/2 binding = 118 +/- 34 min), and gastric ulcers (ulcer mean T 1/2 binding = 135 +/- 59 min). Duodenal ulcers were not successfully imaged. Normal subjects showed no abnormal localization of sucralfate, and esophageal and gastric clearances were rapid.« less

Selenium and Preeclampsia: a Systematic Review and Meta-analysis.

PubMed

Xu, Min; Guo, Dan; Gu, Hao; Zhang, Li; Lv, Shuyan

2016-06-01

Conflicting results exist between selenium concentration and preeclampsia. The role of selenium in the development of preeclampsia is unclear. We conducted a meta-analysis to compare the blood selenium level in patients with preeclampsia and healthy pregnant women, and to determine the effectiveness of selenium supplementation in preventing preeclampsia. We searched PubMed, ScienceDirect, the Cochrane Library, and relevant references for English language literature up to November 25, 2014. Mean difference from observational studies and relative risk from randomized controlled trials were meta-analyzed by a random-effect model. Thirteen observational studies with 1515 participants and 3 randomized controlled trials with 439 participants were included in the meta-analysis. Using a random-effect model, a statistically significant difference in blood selenium concentration of -6.47 μg/l (95 % confidence interval (CI) -11.24 to -1.7, p = 0.008) was seen after comparing the mean difference of observational studies. In randomized controlled trials, using a random-effect model, the relative risk for preeclampsia was 0.28 (0.09 to 0.84) for selenium supplementation (p = 0.02). Evidence from observational studies indicates an inverse association of blood selenium level and the risk of preeclampsia. Supplementation with selenium significantly reduces the incidence of preeclampsia. However, more prospective clinical trials are required to assess the association between selenium supplementation and preeclampsia and to determine the dose, beginning time, and duration of selenium supplementation.

Structural motif screening reveals a novel, conserved carbohydrate-binding surface in the pathogenesis-related protein PR-5d.

PubMed

Doxey, Andrew C; Cheng, Zhenyu; Moffatt, Barbara A; McConkey, Brendan J

2010-08-03

Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins. The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.

Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma.

PubMed

Yanhua, Wang; Hao, Hang; Li, Yan; Zhang, Shengmin

2016-04-01

Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Novel selenium-substituted hydroxyapatite nanoparticles (SeHAN) were designed to serve as anticancer agent. The authors examined the nanoparticles by physicochemical techniques. The in vivo efficacy and toxicity of these nanoparticles were also investigated on a nude mice model of human hepatocellular carcinoma. The results showed that the selenite ions can be incorporated into the hydroxyapatite lattice facilely. They exhibited bundles of needles shape with a size of 160-200 nm. In the in vivo study, they showed better survival advantage. The overall survival rate of nude mice in the control, pure hydroxyapatite and SeHAN group were 50.00%, 76.92%, and 100.00% respectively. Blood biochemical studies showed that SeHAN group had significantly lower toxicities on the liver and kidney functions. Histopathological studies confirmed that massive tumor necrosis and calcium deposition were evident after SeHAN treatment. Moreover, immunohistochemistry and Western blot assay showed significantly reduced expression of the Ki-67, VEGF and MMP-9 protein in the SeHAN group. Taken together, these results suggest that the selenium-substituted hydroxyapatite nanoparticles could be a new type of promising anticancer agent to provide both survival advantage and lower toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of selenizing conditions for Seleno-Lentinan and its characteristics.

PubMed

Ren, Guangming; Li, Koukou; Hu, Yang; Yu, Min; Qu, Juanjuan; Xu, Xiuhong

2015-11-01

Lentinan was successfully modified with nitric acid-sodium selenite method based on L9(3(4)) orthogonal experiments. The optimum selenizing conditions were obtained according to selenium conversion rate as follows: Lentinan of 1.0g, pH of 4.5, temperature of 70°C and sodium selenite of 1.50g. The antioxidant activity assays in vitro (DPPH, reducing power, superoxide radicals and hydroxyl radicals) proved that Lentinan had stronger antioxidant activity after selenizing. The elevations of serum alanine aminotransferase and aspartate aminotransferase, as well as the abnormal hepatic architecture, verified that oral administration of Seleno-Lentinan (SL2-1) markedly alleviated oxidative damage in the liver of mice induced by D-gal. In addition, SL2-1 significantly increased total antioxidant capacity, activities and protein expressions of catalase and glutathione peroxidase and lowered malondialdehyde levels in serum and liver. Fourier transform infrared spectroscopy analysis indicated that selenium of SL2-1 was mostly existed as the formations of OSeO, SeO and SeOC. Scanning electron microscope coupled with energy dispersive X-ray spectroscopy analysis revealed that the surface structure and elemental components of Lentinan significantly changed after selenizing. The results are instructive for the development of organic selenium-supplement resource. Copyright © 2015 Elsevier B.V. All rights reserved.

Nano-selenium and its nanomedicine applications: a critical review

PubMed Central

Hosnedlova, Bozena; Kepinska, Marta; Skalickova, Sylvie; Fernandez, Carlos; Ruttkay-Nedecky, Branislav; Peng, Qiuming; Baron, Mojmir; Melcova, Magdalena; Opatrilova, Radka; Zidkova, Jarmila; Bjørklund, Geir; Sochor, Jiri; Kizek, Rene

2018-01-01

Traditional supplements of selenium generally have a low degree of absorption and increased toxicity. Therefore, it is imperative to develop innovative systems as transporters of selenium compounds, which would raise the bioavailability of this element and allow its controlled release in the organism. Nanoscale selenium has attracted a great interest as a food additive especially in individuals with selenium deficiency, but also as a therapeutic agent without significant side effects in medicine. This review is focused on the incorporation of nanotechnological applications, in particular exploring the possibilities of a more effective way of administration, especially in selenium-deficient organisms. In addition, this review summarizes the survey of knowledge on selenium nanoparticles, their biological effects in the organism, advantages, absorption mechanisms, and nanotechnological applications for peroral administration. PMID:29692609

Search for relevant indications for selenium supplementation in thyroid diseases.

PubMed

Wojciechowska-Durczynska, Katarzyna; Lewinski, Andrzej

2017-08-01

Selenium plays a significant role in the thyroid function and its deficiency is considered by some authors to be a cause of thyroid disorders. The potential therapeutic influence of selenium supplementation in thyroid disease was investigated in several studies and some results were encouraging, however results were inconsistent and did not allow conclusion to be drawn. For that reason, we have performed a review study on relevance of selenium supplementation in thyroid disease. Till now, there is no strong evidence that selenium supplementation leads to clinical improvement in the course of autoimmune thyroiditis, nodular goitre or thyroid cancer. On the other hand, there is some evidence that selenium is effective in the treatment of orbitopathy; thus, the European Group on Graves' Orbitopathy (EUGOGO) recommends selenium administration in mild active orbitopathy.

Selenium as an essential micronutrient: roles in cell cycle and apoptosis.

PubMed

Zeng, Huawei

2009-03-23

Selenium is an essential trace element for humans and animals, and selenium deficiency is associated with several disease conditions such as immune impairment. In addition, selenium intakes that are greater than the recommended daily allowance (RDA) appear to protect against certain types of cancers. In humans and animals, cell proliferation and death must be regulated to maintain tissue homeostasis, and it has been well documented that numerous human diseases are directly related to the control of cell cycle progression and apoptosis. Thus, the elucidation of the mechanisms by which selenium regulates the cell cycle and apoptosis can lead to a better understanding of the nature of selenium's essentiality and its role in disease prevention. This article reviews the status of knowledge concerning the effect of selenium on cell cycle and apoptosis.

Ion-binding properties of Calnuc, Ca2+ versus Mg2+--Calnuc adopts additional and unusual Ca2+-binding sites upon interaction with G-protein.

PubMed

Kanuru, Madhavi; Samuel, Jebakumar J; Balivada, Lavanya M; Aradhyam, Gopala K

2009-05-01

Calnuc is a novel, highly modular, EF-hand containing, Ca(2+)-binding, Golgi resident protein whose functions are not clear. Using amino acid sequences, we demonstrate that Calnuc is a highly conserved protein among various organisms, from Ciona intestinalis to humans. Maximum homology among all sequences is found in the region that binds to G-proteins. In humans, it is known to be expressed in a variety of tissues, and it interacts with several important protein partners. Among other proteins, Calnuc is known to interact with heterotrimeric G-proteins, specifically with the alpha-subunit. Herein, we report the structural implications of Ca(2+) and Mg(2+) binding, and illustrate that Calnuc functions as a downstream effector for G-protein alpha-subunit. Our results show that Ca(2+) binds with an affinity of 7 mum and causes structural changes. Although Mg(2+) binds to Calnuc with very weak affinity, the structural changes that it causes are further enhanced by Ca(2+) binding. Furthermore, isothermal titration calorimetry results show that Calnuc and the G-protein bind with an affinity of 13 nm. We also predict a probable function for Calnuc, that of maintaining Ca(2+) homeostasis in the cell. Using Stains-all and terbium as Ca(2+) mimic probes, we demonstrate that the Ca(2+)-binding ability of Calnuc is governed by the activity-based conformational state of the G-protein. We propose that Calnuc adopts structural sites similar to the ones seen in proteins such as annexins, c2 domains or chromogrannin A, and therefore binds more calcium ions upon binding to Gialpha. With the number of organelle-targeted G-protein-coupled receptors increasing, intracellular communication mediated by G-proteins could become a new paradigm. In this regard, we propose that Calnuc could be involved in the downstream signaling of G-proteins.

In Situ Protein Binding Assay Using Fc-Fusion Proteins.

PubMed

Padmanabhan, Nirmala; Siddiqui, Tabrez J

2017-01-01

This protocol describes an in situ protein-protein interaction assay between tagged recombinant proteins and cell-surface expressed synaptic proteins. The assay is arguably more sensitive than other traditional protein binding assays such as co-immunoprecipitation and pull-downs and provides a visual readout for binding. This assay has been widely used to determine the dissociation constant of binding of trans-synaptic adhesion proteins. The step-wise description in the protocol should facilitate the adoption of this method in other laboratories.

Selenium exposure and depressive symptoms: the Coronary Artery Risk Development in Young Adults Trace Element Study

PubMed Central

Colangelo, Laura A; He, Ka; Whooley, Mary A; Daviglus, Martha L.; Morris, Steven; Liu, Kiang

2014-01-01

Selenium is an essential trace element important to neurotransmission, but toxic at high levels. Some studies suggest beneficial effects on mood. We assessed the association of selenium exposure with presence of depressive symptoms. Selenium exposure was measured in toenail samples collected in 1987 from 3,735 US participants (age 20–32 years) and depressive symptoms assessed in 1990, 1995, 2000, 2005, and 2010 using the Center for Epidemiologic Studies Depression Scale (CES-D). Binary and polytomous logistic regression models were used to assess the relation of log2(selenium) and selenium quintiles with presence of depressive symptoms (CES-D score ≥ 27 or on antidepressant medication). Relative to selenium quintile 1, the adjusted odds ratio (OR) for having depressive symptoms in 1990 for quintile 5 was 1.59 (95% CI: 1.01, 2.51) and a unit increase in log2(selenium), which represents a doubling of the selenium level, was associated with an OR=2.03 (95% CI: 1.12, 3.70). When examining 1, 2 or 3+ exams vs no exams with symptoms, the OR for quintile 5 was 1.73 (1.04, 2.89) for 3+ exams and for one exam and two exams, there were no associations. In a generalized estimating equations longitudinal model, a doubling of the selenium level was associated with a 56% higher odds of having depressive symptoms at an exam. Contrary to previously reported findings related to mood, higher level of selenium exposure was associated with presence of elevated depressive symptoms. More research is needed to elucidate the role of selenium in depressive disorders. PMID:24560993

Effect of Selenium Supplementation on Recurrent Hyperthyroidism Caused by Graves' Disease: A Prospective Pilot Study.

PubMed

Wang, L; Wang, B; Chen, S R; Hou, X; Wang, X F; Zhao, S H; Song, J Q; Wang, Y G

2016-09-01

The effect of selenium supplementation on recurrent hyperthyroidism caused by Graves' disease is unclear. Our study aimed to assess the efficacy of selenium supplementation therapy on recurrent Graves' disease. Forty-one patients with recurrent Graves' disease were enrolled in this study. All patients received the routine treatment using methimazole (MMI), while patients allocated to the selenium group received additional selenium therapy for 6 months. The influence of selenium supplementation on the concentrations of thyroid stimulating hormone (TSH), anti-TSH-receptor antibodies (TRAb), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed. The remission rate was also compared between 2 groups. There was no obvious difference in the demographic data and the levels of serum FT4, FT3, TSH, and TRAb between the 2 groups at baseline. Both FT4 and FT3 decreased more at 2 months in the selenium group than the controls, while the TSH level increased more in patients receiving selenium supplementation (p<0.05). The TRAb level was significantly lower in patients receiving selenium supplementation (2.4 IU/l vs. 5.6 IU/l, p=0.04). The percentages of patients with normal TRAb level at 6 months was also significantly higher in the selenium group (19.0 vs. 0%, p=0.016). Kaplan-Meier survival curve showed patients receiving selenium supplementation had a significantly higher rate of remission than controls (Log-rank test p=0.008). In conclusion, selenium supplementation can enhance the effect of antithyroid drugs in patients with recurrent Graves' disease. Randomized trials with large number of participants are needed to validate the finding above. © Georg Thieme Verlag KG Stuttgart · New York.

Role of Selenium from Different Sources in Prevention of Pulmonary Arterial Hypertension Syndrome in Broiler Chickens.

PubMed

Zamani Moghaddam, A K; Mehraei Hamzekolaei, M H; Khajali, F; Hassanpour, H

2017-11-01

Pulmonary arterial hypertension (PAH) syndrome in broilers is associated with hypoxia, which prevails at high altitude. Oxidative stress is the pathogenic mechanism underlying PAH. Because selenium is key element in the structure of antioxidant enzymes, we evaluated pulmonary hypertensive responses in broiler chickens fed with diets supplemented with organic or nano-selenium. One hundred forty-four broilers (starting at 5 days old) were fed with (i) control group: birds received a standard diet; (ii) nano-selenium group: birds were fed with basal diet supplemented with nano-selenium at 0.3 mg/kg; and (iii) organic selenium group: birds received basal diet supplemented with organic selenium at 0.3 mg/kg. We assessed growth performance, carcass characteristics, antioxidant variables, blood parameters, and small intestine morphology. Although Se supplementation did not affect growth performance, carcass traits, and organ weight (P > 0.05), the right to total ventricular weight ratio (RV:TV), malondialdehyde concentration in the liver, and heterophil to lymphocyte ratio were significantly lower in the nano-selenium group relative to the control (P < 0.05). Chickens that received nano-selenium also elicited significantly higher antibody titers after 24 h of an injection of sheep red blood cells (P < 0.05). Nano-selenium supplementation also significantly increased villus height, absorptive surface area, and lamina propria thickness relative to the control (P < 0.05) in different segments of the small intestine. In contrast, organic selenium supplement improved intestinal morphometry only in the jejunum. We conclude that dietary supplementation of 0.30 mg/kg nano-selenium could prevent right ventricular hypertrophy as reflected by reduced RV:TV, reduced levels of lipid peroxidation in the liver, and improved gut function.

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

PubMed Central

Choe, Weonu; Durgannavar, Trishaladevi A.; Chung, Sang J.

2016-01-01

The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed. PMID:28774114

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Retinol-binding protein immunological test system...

Lipid-binding proteins modulate ligand-dependent trans-activation by peroxisome proliferator-activated receptors and localize to the nucleus as well as the cytoplasm.

PubMed

Helledie, T; Antonius, M; Sorensen, R V; Hertzel, A V; Bernlohr, D A; Kølvraa, S; Kristiansen, K; Mandrup, S

2000-11-01

Peroxisome proliferator-activated receptors (PPARs) are activated by a variety of fatty acids, eicosanoids, and hypolipidemic and insulin-sensitizing drugs. Many of these compounds bind avidly to members of a family of small lipid-binding proteins, the fatty acid-binding proteins (FABPs). Fatty acids are activated to CoA esters, which bind with high affinity to the acyl-CoA-binding protein (ACBP). Thus, the availability of known and potential PPAR ligands may be regulated by lipid-binding proteins. In this report we show by transient transfection of CV-1 cells that coexpression of ACBP and adipocyte lipid-binding protein (ALBP) exerts a ligand- and PPAR subtype-specific attenuation of PPAR-mediated trans-activation, suggesting that lipid-binding proteins, when expressed at high levels, may function as negative regulators of PPAR activation by certain ligands. Expression of ACBP, ALBP, and keratinocyte lipid-binding protein (KLBP) is induced during adipocyte differentiation, a process during which PPARgamma plays a prominent role. We present evidence that endogenous ACBP, ALBP, and KLBP not only localize to the cytoplasm but also exhibit a prominent nuclear localization in 3T3-L1 adipocytes. In addition, forced expression of ACBP, ALBP, and KLBP in CV-1 cells resulted in a substantial accumulation of all three proteins in the nucleus. These results suggest that lipid-binding proteins, contrary to the general assumption, may exert their action in the nucleus as well as in the cytoplasm.

Unconventional RNA-binding proteins: an uncharted zone in RNA biology.

PubMed

Albihlal, Waleed S; Gerber, André P

2018-06-16

RNA-binding proteins play essential roles in the post-transcriptional regulation of gene expression. While hundreds of RNA-binding proteins can be predicted computationally, the recent introduction of proteome-wide approaches has dramatically expanded the repertoire of proteins interacting with RNA. Besides canonical RNA-binding proteins that contain characteristic RNA-binding domains, many proteins that lack such domains but have other well-characterised cellular functions were identified; including metabolic enzymes, heat shock proteins, kinases, as well as transcription factors and chromatin-associated proteins. In the context of these recently published RNA-protein interactome datasets obtained from yeast, nematodes, flies, plants and mammalian cells, we discuss examples for seemingly evolutionary conserved "unconventional" RNA-binding proteins that act in central carbon metabolism, stress response or regulation of transcription. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The hepta-beta-glucoside elicitor-binding proteins from legumes represent a putative receptor family.

PubMed

Mithöfer, A; Fliegmann, J; Neuhaus-Url, G; Schwarz, H; Ebel, J

2000-08-01

The ability of legumes to recognize and respond to beta-glucan elicitors by synthesizing phytoalexins is consistent with the existence of a membrane-bound beta-glucan-binding site. Related proteins of approximately 75 kDa and the corresponding mRNAs were detected in various species of legumes which respond to beta-glucans. The cDNAs for the beta-glucan-binding proteins of bean and soybean were cloned. The deduced 75-kDa proteins are predominantly hydrophilic and constitute a unique class of glucan-binding proteins with no currently recognizable functional domains. Heterologous expression of the soybean beta-glucan-binding protein in tomato cells resulted in the generation of a high-affinity binding site for the elicitor-active hepta-beta-glucoside conjugate (Kd = 4.5 nM). Ligand competition experiments with the recombinant binding sites demonstrated similar ligand specificities when compared with soybean. In both soybean and transgenic tomato, membrane-bound, active forms of the glucan-binding proteins coexist with immunologically detectable, soluble but inactive forms of the proteins. Reconstitution of a soluble protein fraction into lipid vesicles regained beta-glucoside-binding activity but with lower affinity (Kd = 130 nM). We conclude that the beta-glucan elicitor receptors of legumes are composed of the 75 kDa glucan-binding proteins as the critical components for ligand-recognition, and of an as yet unknown membrane anchor constituting the plasma membrane-associated receptor complex.

Isolation from genomic DNA of sequences binding specific regulatory proteins by the acceleration of protein electrophoretic mobility upon DNA binding.

PubMed

Subrahmanyam, S; Cronan, J E

1999-01-21

We report an efficient and flexible in vitro method for the isolation of genomic DNA sequences that are the binding targets of a given DNA binding protein. This method takes advantage of the fact that binding of a protein to a DNA molecule generally increases the rate of migration of the protein in nondenaturing gel electrophoresis. By the use of a radioactively labeled DNA-binding protein and nonradioactive DNA coupled with PCR amplification from gel slices, we show that specific binding sites can be isolated from Escherichia coli genomic DNA. We have applied this method to isolate a binding site for FadR, a global regulator of fatty acid metabolism in E. coli. We have also isolated a second binding site for BirA, the biotin operon repressor/biotin ligase, from the E. coli genome that has a very low binding efficiency compared with the bio operator region.

Field screening of water, soil, bottom sediment, and biota associated with irrigation drainage in the Dolores Project and the Macos River basin, southwestern Colorado, 1994

USGS Publications Warehouse

Butler, D.L.; Osmundson, B.C.; Krueger, R.P.

1997-01-01

A reconnaissance investigation for the National Irrigation Water Quality Program in 1990 indicated elevated selenium concentrations in some water and biota samples collected in the Dolores Project in southwestern Colorado. High selenium concentrations also were indicated in bird samples collected in the Mancos Project in 1989. In 1994, field screenings were done in parts of the Dolores Project and Mancos River Basin to collect additional selenium data associated with irrigation inthose areas. Selenium is mobilized from soils in newly irrigated areas of the Dolores Project called the Dove Creek area, which includes newly (since 1987) irrigated land north of Cortez and south of Dove Creek.Selenium was detected in 18 of 20stream samples, and the maximum concentration was 12micrograms per liter. The Dove Creek area is unique compared to other study areas of the National Irrigation Water Quality Program becauseselenium concentrations probably are indicative of initial leaching conditions in a newly irrigated area.Selenium concentrations in nine shallow soil samples from the Dove Creek area ranged from 0.13 to 0.20 micrograms per gram. Selenium concentrations in bottom sediment from six ponds were less than the level of concern for fish and wildlife of 4 micrograms per gram. Many biota samples collected in the Dove Creek area had elevated selenium concentrations when compared to various guidelines and effect levels,although selenium concentrations in water, soil, and bottom sediment were relatively low. Selenium concentrations in 12 of 14 aquatic-invertebratesamples from ponds exceeded 3 micrograms per gram dry weight, a dietary guideline for protection of fish and wildlife. The mean seleniumconcentration of 10.3 micrograms per gram dry weight in aquatic bird eggs exceeded the guideline for reduced hatchability of 8 micrograms per gramdry weight. Two ponds in the Dove Creek area had a high selenium hazard rating based on a new protocol for assessing selenium hazard in theenvironment; however, waterfowl were reproducing at the two ponds. Three tributary streams of Mc Elmo Creek that drain irrigated areas of the Montezuma Valley south of the creek were sampled in 1994. Mud Creek probably is the largest source of selenium to Mc Elmo Creek. Most biota samples from Mud Creek had elevated selenium concentrations when compared to guidelines for dietary items and freshwater fish. Selenium concentrations in water samples collected in the Mancos River Basin upstream from Navajo Wash, which includes the Mancos Project, ranged from less than 1 to 10 micrograms per liter. Mud Creek contributed about 74 percent of the selenium load to the upper Mancos River in March 1994.Selenium concentrations were much higher in Navajo Wash; a sample collected in March had 97 micrograms per liter of selenium. Bottom-sediment samples from two ponds in the Mancos Projectexceeded the concentration of concern of 4 micrograms per gram. The highest selenium concentrations in biota samples from streams in the Mancos River Basin were for samples from Navajo Wash. Mostconcentrations in biota in the upper Mancos River Basin were less than guidelines. Mean selenium concentrations in eggs from aquatic birds collected at three ponds in the Mancos Project slightly exceed the guideline associated with reduced hatchability.Five bird livers had a mean selenium concentration of 32.6 micrograms per gram dry weight, whichslightly exceeded the mean concentration of 30 micrograms per gram dry weight that is associated with reproductive impairment. Two of the pondshad a high selenium hazard rating; however, mallard reproduction was observed in 1994 at one of the ponds that had a high selenium-hazard rating.

Engineered proteins as specific binding reagents.

PubMed

Binz, H Kaspar; Plückthun, Andreas

2005-08-01

Over the past 30 years, monoclonal antibodies have become the standard binding proteins and currently find applications in research, diagnostics and therapy. Yet, monoclonal antibodies now face strong competition from synthetic antibody libraries in combination with powerful library selection technologies. More recently, an increased understanding of other natural binding proteins together with advances in protein engineering, selection and evolution technologies has also triggered the exploration of numerous other protein architectures for the generation of designed binding molecules. Valuable protein-binding scaffolds have been obtained and represent promising alternatives to antibodies for biotechnological and, potentially, clinical applications.

Interspecific and intraspecific variation in selenium:mercury molar ratios in saltwater fish from the Aleutians: Potential protection on mercury toxicity by selenium

PubMed Central

Burger, Joanna; Gochfeld, Michael; Jeitner, Christian; Donio, Mark; Pittfield, Taryn

2014-01-01

A number of factors affect the consumption risk from mercury in fish, including mercury levels, seasonal patterns of mercury concentrations, human consumption patterns, and sensitive populations (e.g. pregnant women, fetuses, young children, and yet unknown genetic factors). Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for saltwater fish. We examine levels of mercury and selenium in several species of fish and seabirds from the Aleutians (Alaska), determine selenium:mercury molar ratios, and examine species-specific and individual variation in the ratios as a means of exploring the use of the ratio in risk assessment and risk management. Variation among species was similar for mercury and selenium. There was significant inter-specific and intraspecific variation in selenium:mercury molar ratios for fish, and for birds. The mean selenium:mercury molar ratios for all fish and bird species were above 1, meaning there was an excess of selenium relative to mercury. It has been suggested that an excess of selenium confers some protective advantage for salt water fish, although the degree of excess necessary is unclear. The selenium:mercury molar ratio was significantly correlated negatively with total length for most fish species, but not for dolly varden. Some individuals of Pacific cod, yellow irish lord, rock greenling, Pacific halibut, dolly varden, and to a lesser extent, flathead sole, had selenium:mercury ratios below 1. No bird muscle had an excess of mercury (ratio below 1), and only glaucous-winged gull and pigeon guillemot had ratios between 1 and 5. There was a great deal of variation in selenium:mercury molar ratios within fish species, and within bird species, making it difficult and impractical to use these ratios in risk assessment or management, for fish advisories, or for consumers, particularly given the difficulty of interpreting the ratios. PMID:22664537

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muecke, Ralph; Schomburg, Lutz; Glatzel, Michael

Purpose: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. Methods and Materials: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84{mu}g/L were randomized before RT either to receive 500 {mu}g of selenium (in the form of sodium selenite [selenase (registered) , biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouthmore » on the days of RT and 300 {mu}g of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. Results: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. Conclusions: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.« less

Odorant-binding proteins from a primitive termite.

PubMed

Ishida, Yuko; Chiang, Vicky P; Haverty, Michael I; Leal, Walter S

2002-09-01

Hitherto, odorant-binding proteins (OBPs) have been identified from insects belonging to more highly evolved insect orders (Lepidoptera, Coleoptera, Diptera, Hymenoptera, and Hemiptera), whereas only chemosensory proteins have been identified from more primitive species, such as orthopteran and phasmid species. Here, we report for the first time the isolation and cloning of odorant-binding proteins from a primitive termite species, the dampwood termite. Zootermopsis nevadensis nevadensis (Isoptera: Termopsidae). A major antennae-specific protein was detected by native PAGE along with four other minor proteins, which were also absent in the extract from control tissues (hindlegs). Multiple cDNA cloning led to the full characterization of the major antennae-specific protein (ZnevOBP1) and to the identification of two other antennae-specific cDNAs, encoding putative odorant-binding proteins (ZnevOBP2 and ZnevOBP3). N-terminal amino acid sequencing of the minor antennal bands and cDNA cloning showed that olfaction in Z. n. nevadensis may involve multiple odorant-binding proteins. Database searches suggest that the OBPs from this primitive termite are homologues of the pheromone-binding proteins from scarab beetles and antennal-binding proteins from moths.

Roles of Copper-Binding Proteins in Breast Cancer.

PubMed

Blockhuys, Stéphanie; Wittung-Stafshede, Pernilla

2017-04-20

Copper ions are needed in several steps of cancer progression. However, the underlying mechanisms, and involved copper-binding proteins, are mainly elusive. Since most copper ions in the body (in and outside cells) are protein-bound, it is important to investigate what copper-binding proteins participate and, for these, how they are loaded with copper by copper transport proteins. Mechanistic information for how some copper-binding proteins, such as extracellular lysyl oxidase (LOX), play roles in cancer have been elucidated but there is still much to learn from a biophysical molecular viewpoint. Here we provide a summary of copper-binding proteins and discuss ones reported to have roles in cancer. We specifically focus on how copper-binding proteins such as mediator of cell motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects. Because of the importance of copper for invasion/migration processes, which are key components of cancer metastasis, further insights into the actions of copper-binding proteins may provide new targets to combat cancer.

Selenium-Enriched Foods Are More Effective at Increasing Glutathione Peroxidase (GPx) Activity Compared with Selenomethionine: A Meta-Analysis

PubMed Central

Bermingham, Emma N.; Hesketh, John E.; Sinclair, Bruce R.; Koolaard, John P.; Roy, Nicole C.

2014-01-01

Selenium may play a beneficial role in multi-factorial illnesses with genetic and environmental linkages via epigenetic regulation in part via glutathione peroxidase (GPx) activity. A meta-analysis was undertaken to quantify the effects of dietary selenium supplementation on the activity of overall GPx activity in different tissues and animal species and to compare the effectiveness of different forms of dietary selenium. GPx activity response was affected by both the dose and form of selenium (p < 0.001). There were differences between tissues on the effects of selenium supplementation on GPx activity (p < 0.001); however, there was no evidence in the data of differences between animal species (p = 0.95). The interactions between dose and tissue, animal species and form were significant (p < 0.001). Tissues particularly sensitive to changes in selenium supply include red blood cells, kidney and muscle. The meta-analysis identified that for animal species selenium-enriched foods were more effective than selenomethionine at increasing GPx activity. PMID:25268836

Special AT-rich sequence binding protein 1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma.

PubMed

Ma, Jun; Wu, Kaiming; Zhao, Zhenxian; Miao, Rong; Xu, Zhe

2017-03-01

Esophageal squamous cell carcinoma is one of the most aggressive malignancies worldwide. Special AT-rich sequence binding protein 1 is a nuclear matrix attachment region binding protein which participates in higher order chromatin organization and tissue-specific gene expression. However, the role of special AT-rich sequence binding protein 1 in esophageal squamous cell carcinoma remains unknown. In this study, western blot and quantitative real-time polymerase chain reaction analysis were performed to identify differentially expressed special AT-rich sequence binding protein 1 in a series of esophageal squamous cell carcinoma tissue samples. The effects of special AT-rich sequence binding protein 1 silencing by two short-hairpin RNAs on cell proliferation, migration, and invasion were assessed by the CCK-8 assay and transwell assays in esophageal squamous cell carcinoma in vitro. Special AT-rich sequence binding protein 1 was significantly upregulated in esophageal squamous cell carcinoma tissue samples and cell lines. Silencing of special AT-rich sequence binding protein 1 inhibited the proliferation of KYSE450 and EC9706 cells which have a relatively high level of special AT-rich sequence binding protein 1, and the ability of migration and invasion of KYSE450 and EC9706 cells was distinctly suppressed. Special AT-rich sequence binding protein 1 could be a potential target for the treatment of esophageal squamous cell carcinoma and inhibition of special AT-rich sequence binding protein 1 may provide a new strategy for the prevention of esophageal squamous cell carcinoma invasion and metastasis.

Optimal serum selenium concentrations are associated with lower depressive symptoms and negative mood among young adults.

PubMed

Conner, Tamlin S; Richardson, Aimee C; Miller, Jody C

2015-01-01

There is evidence that low, and possibly high, selenium status is associated with depressed mood. More evidence is needed to determine whether this pattern occurs in young adults with a wide range of serum concentrations of selenium. The aim of this study was to determine if serum selenium concentration is associated with depressive symptoms and daily mood states in young adults. A total of 978 young adults (aged 17-25 y) completed the Center for Epidemiological Studies-Depression scale and reported their negative and positive mood daily for 13 d using an Internet diary. Serum selenium concentration was determined by inductively coupled plasma mass spectrometry. ANCOVA and regression models tested the linear and curvilinear associations between decile of serum selenium concentration and mood outcomes, controlling for age, gender, ethnicity, BMI, and weekly alcohol intake. Smoking and childhood socioeconomic status were further controlled in a subset of participants. The mean ± SD serum selenium concentration was 82 ± 18 μg/L and ranged from 49 to 450 μg/L. Participants with the lowest serum selenium concentration (62 ± 4 μg/L; decile 1) and, to a lesser extent, those with the highest serum selenium concentration (110 ± 38 μg/L; decile 10) had significantly greater adjusted depressive symptoms than did participants with midrange serum selenium concentrations (82 ± 1 to 85 ± 1 μg/L; deciles 6 and 7). Depressive symptomatology was lowest at a selenium concentration of ∼85 μg/L. Patterns for negative mood were similar but more U-shaped. Positive mood showed an inverse U-shaped association with selenium, but this pattern was less consistent than depressive symptoms or negative mood. In young adults, an optimal range of serum selenium between ∼82 and 85 μg/L was associated with reduced risk of depressive symptomatology. This range approximates the values at which glutathione peroxidase is maximal, suggesting that future research should investigate antioxidant pathways linking selenium to mood. This trial was registered with the Australian New Zealand Clinical Trials Registry as ACTRN12613000773730. © 2015 American Society for Nutrition.

A pollen-specific novel calmodulin-binding protein with tetratricopeptide repeats

NASA Technical Reports Server (NTRS)

Safadi, F.; Reddy, V. S.; Reddy, A. S.

2000-01-01

Calcium is essential for pollen germination and pollen tube growth. A large body of information has established a link between elevation of cytosolic Ca(2+) at the pollen tube tip and its growth. Since the action of Ca(2+) is primarily mediated by Ca(2+)-binding proteins such as calmodulin (CaM), identification of CaM-binding proteins in pollen should provide insights into the mechanisms by which Ca(2+) regulates pollen germination and tube growth. In this study, a CaM-binding protein from maize pollen (maize pollen calmodulin-binding protein, MPCBP) was isolated in a protein-protein interaction-based screening using (35)S-labeled CaM as a probe. MPCBP has a molecular mass of about 72 kDa and contains three tetratricopeptide repeats (TPR) suggesting that it is a member of the TPR family of proteins. MPCBP protein shares a high sequence identity with two hypothetical TPR-containing proteins from Arabidopsis. Using gel overlay assays and CaM-Sepharose binding, we show that the bacterially expressed MPCBP binds to bovine CaM and three CaM isoforms from Arabidopsis in a Ca(2+)-dependent manner. To map the CaM-binding domain several truncated versions of the MPCBP were expressed in bacteria and tested for their ability to bind CaM. Based on these studies, the CaM-binding domain was mapped to an 18-amino acid stretch between the first and second TPR regions. Gel and fluorescence shift assays performed with CaM and a CaM-binding synthetic peptide further confirmed MPCBP binding to CaM. Western, Northern, and reverse transcriptase-polymerase chain reaction analysis have shown that MPCBP expression is specific to pollen. MPCBP was detected in both soluble and microsomal proteins. Immunoblots showed the presence of MPCBP in mature and germinating pollen. Pollen-specific expression of MPCBP, its CaM-binding properties, and the presence of TPR motifs suggest a role for this protein in Ca(2+)-regulated events during pollen germination and growth.

Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl-like molecules binding.

PubMed

Isvoran, Adriana; Craciun, Dana; Martiny, Virginie; Sperandio, Olivier; Miteva, Maria A

2013-06-14

Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are small organic molecules known to mimic one face of protein-binding alpha-helical peptides. In this work we focus on several PPIs mediated by alpha-helical peptides. We performed computational sequence- and structure-based analyses in order to evaluate several key physicochemical and surface properties of proteins known to interact with alpha-helical peptides and/or terphenyl and its derivatives. Sequence-based analysis revealed low sequence identity between some of the analyzed proteins binding alpha-helical peptides. Structure-based analysis was performed to calculate the volume, the fractal dimension roughness and the hydrophobicity of the binding regions. Besides the overall hydrophobic character of the binding pockets, some specificities were detected. We showed that the hydrophobicity is not uniformly distributed in different alpha-helix binding pockets that can help to identify key hydrophobic hot spots. The presence of hydrophobic cavities at the protein surface with a more complex shape than the entire protein surface seems to be an important property related to the ability of proteins to bind alpha-helical peptides and low molecular weight mimetics. Characterization of similarities and specificities of PPI binding sites can be helpful for further development of small molecules targeting alpha-helix binding proteins.

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, Gisela K.

1997-01-01

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, G.K.

1997-04-29

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

Impact of germline and somatic missense variations on drug binding sites.

PubMed

Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

2017-03-01

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and germline nsSNVs that disrupt these binding sites can provide valuable knowledge for personalized medicine treatment. A web portal is available where nsSNVs from individual patient can be checked by scanning against DrugVar to determine whether any of the SNVs affect the binding of any drug in the database.

Simple method for determination of selenium in biological materials by flameless atomic-absorption spectrometry using a carbon-tube atomizer.

PubMed

Ishizaki, M

1978-03-01

A method for determination of selenium in biological materials by flameless atomic-absorption spectrometry using a carbon-tube atomizer is described. The sample is burned by an oxygen-flask combustion procedure, the resulting solution is treated with a cation-exchange resin to eliminate interfering cations, the selenium is extracted with dithizone in carbon tetrachloride and the resulting selenium dithizonate is combined with nickel nitrate in the carbon tube to enhance the sensitivity for selenium and avoid volatilization losses. The method measures selenium concentrations as low as 0.01 mug/g with a relative standard deviation of 8%.

Improved selenium recovery from tissue with modified sample decomposition

USGS Publications Warehouse

Brumbaugh, W. G.; Walther, M.J.

1991-01-01

The present paper describes a simple modification of a recently reported decomposition method for determination of selenium in biological tissue by hydride generation atomic absorption. The modified method yielded slightly higher selenium recoveries (3-4%) for selected reference tissues and fish tissue spiked with selenomethionine. Radiotracer experiments indicated that the addition of a small volume of hydrochloric acid to the wet digestate mixture reduced slight losses of selenium as the sample initially went to dryness before ashing. With the modified method, selenium spiked as selenomethionine behaved more like the selenium in reference tissues than did the inorganic spike forms when this digestion modification was used.

An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Solomon River Basin

USGS Publications Warehouse

May, T.W.; Fairchild, J.F.; Petty, J.D.; Walther, M.J.; Lucero, J.; Delvaux, M.; Manring, J.; Armbruster, M.

2008-01-01

The Solomon River Basin is located in north-central Kansas in an area underlain by marine geologic shales. Selenium is an indigenous constituent of these shales and is readily leached into the surrounding groundwater. Portions of the Basin are irrigated primarily through the pumping of selenium-contaminated groundwater from wells onto fields in agricultural production. Water, sediment, macroinvertebrates, and fish were collected from various sites in the Basin in 1998 and analyzed for selenium. Selenium concentrations were analyzed spatially and temporally and compared to reported selenium toxic effect thresholds for specific ecosystem components: water, sediments, food-chain organisms, and wholebody fish. A selenium aquatic hazard assessment for the Basin was determined based on protocol established by Lemly. Throughout the Basin, water, macroinvertebrate, and whole fish samples exceeded levels suspected of causing reproductive impairment in fish. Population structures of several fish species implied that successful reproduction was occurring; however, the influence of immigration of fish from low-selenium habitats could not be discounted. Site-specific fish reproduction studies are needed to determine the true impact of selenium on fishery resources in the Basin. ?? Springer Science+Business Media B.V. 2007.

Selenium, selenoprotein genes and Crohn's disease in a case-control population from Auckland, New Zealand.

PubMed

Gentschew, Liljana; Bishop, Karen S; Han, Dug Yeo; Morgan, Angharad R; Fraser, Alan G; Lam, Wen Jiun; Karunasinghe, Nishi; Campbell, Bobbi; Ferguson, Lynnette R

2012-09-01

New Zealand has one of the highest incidence rates of Crohn's Disease (CD), whilst the serum selenium status of New Zealanders is amongst the lowest in the world. A prospective case-control study in Auckland, New Zealand considered serum selenium as a potential CD risk factor. Serum selenium levels were significantly lower in CD patients compared to controls (101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL) (p = 5.91 × 10(-8)). Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL, making the average CD patient in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms (SNPs) tested, 13 were found to significantly interact with serum selenium on CD. After adjustment for multiple testing, a significant interaction with serum selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD. It is unclear as to whether lower selenium levels are a cause or an effect of the disease.

Selenium, Selenoprotein Genes and Crohn’s Disease in a Case-Control Population from Auckland, New Zealand

PubMed Central

Gentschew, Liljana; Bishop, Karen S.; Han, Dug Yeo; Morgan, Angharad R.; Fraser, Alan G.; Lam, Wen Jiun; Karunasinghe, Nishi; Campbell, Bobbi; Ferguson, Lynnette R.

2012-01-01

New Zealand has one of the highest incidence rates of Crohn’s Disease (CD), whilst the serum selenium status of New Zealanders is amongst the lowest in the world. A prospective case-control study in Auckland, New Zealand considered serum selenium as a potential CD risk factor. Serum selenium levels were significantly lower in CD patients compared to controls (101.8 ± 1.02 vs. 111.1 ± 1.01 ng/mL) (p = 5.91 × 10−8). Recent detailed studies in the United Kingdom have suggested an optimal serum level around 122 ng/mL, making the average CD patient in New Zealand selenium deficient. Of the 29 single nucleotide polymorphisms (SNPs) tested, 13 were found to significantly interact with serum selenium on CD. After adjustment for multiple testing, a significant interaction with serum selenium on CD was found for three SNPs, namely rs17529609 and rs7901303 in the gene SEPHS1, and rs1553153 in the gene SEPSECS. These three SNPs have not been reported elsewhere as being significantly associated with selenium or CD. It is unclear as to whether lower selenium levels are a cause or an effect of the disease. PMID:23112913

Patterns and plasticity in RNA-protein interactions enable recruitment of multiple proteins through a single site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valley, Cary T.; Porter, Douglas F.; Qiu, Chen

2012-06-28

mRNA control hinges on the specificity and affinity of proteins for their RNA binding sites. Regulatory proteins must bind their own sites and reject even closely related noncognate sites. In the PUF [Pumilio and fem-3 binding factor (FBF)] family of RNA binding proteins, individual proteins discriminate differences in the length and sequence of binding sites, allowing each PUF to bind a distinct battery of mRNAs. Here, we show that despite these differences, the pattern of RNA interactions is conserved among PUF proteins: the two ends of the PUF protein make critical contacts with the two ends of the RNA sites.more » Despite this conserved 'two-handed' pattern of recognition, the RNA sequence is flexible. Among the binding sites of yeast Puf4p, RNA sequence dictates the pattern in which RNA bases are flipped away from the binding surface of the protein. Small differences in RNA sequence allow new modes of control, recruiting Puf5p in addition to Puf4p to a single site. This embedded information adds a new layer of biological meaning to the connections between RNA targets and PUF proteins.« less

The Intrinsically Disordered Regions of the Drosophila melanogaster Hox Protein Ultrabithorax Select Interacting Proteins Based on Partner Topology

PubMed Central

Hsiao, Hao-Ching; Gonzalez, Kim L.; Catanese, Daniel J.; Jordy, Kristopher E.; Matthews, Kathleen S.; Bondos, Sarah E.

2014-01-01

Interactions between structured proteins require a complementary topology and surface chemistry to form sufficient contacts for stable binding. However, approximately one third of protein interactions are estimated to involve intrinsically disordered regions of proteins. The dynamic nature of disordered regions before and, in some cases, after binding calls into question the role of partner topology in forming protein interactions. To understand how intrinsically disordered proteins identify the correct interacting partner proteins, we evaluated interactions formed by the Drosophila melanogaster Hox transcription factor Ultrabithorax (Ubx), which contains both structured and disordered regions. Ubx binding proteins are enriched in specific folds: 23 of its 39 partners include one of 7 folds, out of the 1195 folds recognized by SCOP. For the proteins harboring the two most populated folds, DNA-RNA binding 3-helical bundles and α-α superhelices, the regions of the partner proteins that exhibit these preferred folds are sufficient for Ubx binding. Three disorder-containing regions in Ubx are required to bind these partners. These regions are either alternatively spliced or multiply phosphorylated, providing a mechanism for cellular processes to regulate Ubx-partner interactions. Indeed, partner topology correlates with the ability of individual partner proteins to bind Ubx spliceoforms. Partners bind different disordered regions within Ubx to varying extents, creating the potential for competition between partners and cooperative binding by partners. The ability of partners to bind regions of Ubx that activate transcription and regulate DNA binding provides a mechanism for partners to modulate transcription regulation by Ubx, and suggests that one role of disorder in Ubx is to coordinate multiple molecular functions in response to tissue-specific cues. PMID:25286318

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

PubMed Central

Gumucio, D L; Rood, K L; Gray, T A; Riordan, M F; Sartor, C I; Collins, F S

1988-01-01

The molecular mechanisms responsible for the human fetal-to-adult hemoglobin switch have not yet been elucidated. Point mutations identified in the promoter regions of gamma-globin genes from individuals with nondeletion hereditary persistence of fetal hemoglobin (HPFH) may mark cis-acting sequences important for this switch, and the trans-acting factors which interact with these sequences may be integral parts in the puzzle of gamma-globin gene regulation. We have used gel retardation and footprinting strategies to define nuclear proteins which bind to the normal gamma-globin promoter and to determine the effect of HPFH mutations on the binding of a subset of these proteins. We have identified five proteins in human erythroleukemia cells (K562 and HEL) which bind to the proximal promoter region of the normal gamma-globin gene. One factor, gamma CAAT, binds the duplicated CCAAT box sequences; the -117 HPFH mutation increases the affinity of interaction between gamma CAAT and its cognate site. Two proteins, gamma CAC1 and gamma CAC2, bind the CACCC sequence. These proteins require divalent cations for binding. The -175 HPFH mutation interferes with the binding of a fourth protein, gamma OBP, which binds an octamer sequence (ATGCAAAT) in the normal gamma-globin promoter. The HPFH phenotype of the -175 mutation indicates that the octamer-binding protein may play a negative regulatory role in this setting. A fifth protein, EF gamma a, binds to sequences which overlap the octamer-binding site. The erythroid-specific distribution of EF gamma a and its close approximation to an apparent repressor-binding site suggest that it may be important in gamma-globin regulation. Images PMID:2468996

CXCL4 is a novel nickel-binding protein and augments nickel allergy.

PubMed

Kuroishi, T; Bando, K; Tanaka, Y; Shishido, K; Kinbara, M; Ogawa, T; Muramoto, K; Endo, Y; Sugawara, S

2017-08-01

Nickel (Ni) is the most frequent metal allergen and induces a TH 1 -dependent type-IV allergy. Although Ni 2+ is considered to bind to endogenous proteins, it currently remains unclear whether these Ni-binding proteins are involved in Ni allergy in vivo. We previously reported the adjuvant effects of lipopolysaccharide (LPS) in a Ni allergy mouse model. As LPS induces a number of inflammatory mediators, we hypothesized that Ni-binding protein(s) are also induced by LPS. The objective of this study was to purify and identify Ni-binding protein(s) from serum taken from LPS-injected mice (referred as LPS serum) and examined the augmenting effects of these Ni-binding protein(s) on Ni allergy in an in vivo model. BALB/cA mice were sensitized with an i.p. injection of NiCl 2 and LPS. Ten days after sensitization, mice were challenged with NiCl 2 by an i.d. injection into ear pinnae. Ni-binding protein(s) were purified by Ni-affinity column chromatography and gel filtration. Lipopolysaccharide serum, but not serum taken from saline-injected mice, augmented ear swelling induced by Ni-allergic inflammation. Ni-binding, but not non-binding fraction, purified from LPS serum augmented Ni-allergic inflammation. Mass spectrometry and Western blotting detected CXCL4 in the active fraction. A batch analysis with Ni-sepharose and a surface plasmon resonance analysis revealed direct binding between CXCL4 and Ni 2+ . Recombinant CXCL4 augmented Ni-allergic inflammation and exerted adjuvant effects at the sensitization phase. These results indicate that CXCL4 is a novel Ni-binding protein that augments Ni allergy at the elicitation and sensitization phases. This is the first study to demonstrate that the Ni-binding protein augments Ni allergy in vivo. © 2017 John Wiley & Sons Ltd.

Effect of selenium nanoparticles with different sizes in primary cultured intestinal epithelial cells of crucian carp, Carassius auratus gibelio.

PubMed

Wang, Yanbo; Yan, Xuxia; Fu, Linglin

2013-01-01

Nano-selenium (Se), with its high bioavailability and low toxicity, has attracted wide attention for its potential application in the prevention of oxidative damage in animal tissues. However, the effect of nano-Se of different sizes on the intestinal epithelial cells of the crucian carp (Carassius auratus gibelio) is poorly understood. Our study showed that different sizes and doses of nano-Se have varied effects on the cellular protein contents and the enzyme activities of secreted lactate dehydrogenase, intracellular sodium potassium adenosine triphosphatase, glutathione peroxidase, and superoxide dismutase. It was also indicated that nano-Se had a size-dependent effect on the primary intestinal epithelial cells of the crucian carp. Thus, these findings may bring us a step closer to understanding the size effect and the bioavailability of nano-Se on the intestinal tract of the crucian carp.