Selenoprotein Gene Expression Research Articles

Comprehensive analysis of selenoprotein gene expression and prognostic value in ovarian cancer.

To comprehensively analyze the expression and prognostic value of selenoprotein in ovarian cancer (OV). GEPIA and cBioPortal were used to analyze selenoprotein expression and mutations and copy number variations. Kaplan-Meier plotter and the tumor immune estimation resource were used to evaluate the impact of these genes on clinical prognosis and their correlation with tumor immune infiltration. Compared with normal tissues, the expression of iodothyronine deiodinase 3 (DIO3), glutathione peroxidase 4, SECISBP2, SELM, and SELP was decreased in the four gynecological malignancies. In OV, selenoprotein had the highest number of mutations (309) and mutation frequency (52.91%), whereas the lowest was observed in endometrial cancer (29.72%). DIO3, selenoprotein O (SELO), and selenoprotein T (SELT) are significantly related to the prognosis of OV. Immune infiltration analysis showed that DIO3 was associated with tumor-associated macrophages, SELO with CD4+ T-cells and monocytes, and SELT with T-cells. Enrichment analysis revealed that DIO3 is mainly involved in inflammatory immune responses and the Ras signaling pathway, SELO is primarily related to innate immune responses, and SELT is closely associated with mitochondrial oxidative phosphorylation. This study explored the expression characteristics of 25 selenoprotein in patients with gynecological malignancies and found that DIO3, SELO, and SELT were significantly associated with the prognosis and clinical features of OV, which are potential therapeutic targets.

NRF2 and Thioredoxin Reductase 1 as Modulators of Interactions between Zinc and Selenium.

Selenium and zinc are essential trace elements known to regulate cellular processes including redox homeostasis. During inflammation, circulating selenium and zinc concentrations are reduced in parallel, but underlying mechanisms are unknown. Accordingly, we modulated the zinc and selenium supply of HepG2 cells to study their relationship. HepG2 cells were supplied with selenite in combination with a short- or long-term zinc treatment to investigate intracellular concentrations of selenium and zinc together with biomarkers describing their status. In addition, the activation of the redox-sensitive transcription factor NRF2 was analyzed. Zinc not only increased the nuclear translocation of NRF2 after 2 to 6 h but also enhanced the intracellular selenium content after 72 h, when the cells were exposed to both trace elements. In parallel, the activity and expression of the selenoprotein thioredoxin reductase 1 (TXNRD1) increased, while the gene expression of other selenoproteins remained unaffected or was even downregulated. The zinc effects on the selenium concentration and TXNRD activity were reduced in cells with stable NRF2 knockdown in comparison to control cells. This indicates a functional role of NRF2 in mediating the zinc/selenium crosstalk and provides an explanation for the observed unidirectional behavior of selenium and zinc.

The effect of High-intensity interval training with Portulaca oleracea Hydroalcoholic extract on gene expression of Selenoprotein P (SeP) and insulin resistance in rats with nonalcoholic fatty liver

The effect of High-intensity interval training with Portulaca oleracea Hydroalcoholic extract on gene expression of Selenoprotein P (SeP) and insulin resistance in rats with nonalcoholic fatty liver

A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Molecular Antioxidant Functions are Enhanced in Atlantic Bluefin Tuna (Thunnus Thynnus, L.) Larvae Fed Selenium-Enriched Rotifers Brachionus Rotundiformis.

Selenium (Se) is an essential trace element for fish with more than 40 selenoproteins identified, many exhibiting antioxidant functions. This study investigated the effect of dietary Se supplementation on physiological parameters, selenoprotein and antioxidant enzyme gene expression in Atlantic bluefin tuna (ABT, Thunnus thynnus) larvae. First-feeding ABT larvae were divided into triplicate groups and fed rotifers Brachionus rotundiformis enriched with five different levels of Se (0, 3, 10, 30, and 100 µg Se·L-1) until 14 days after hatching. Both rotifers and ABT larvae effectively accumulated Se achieving maximum levels in the Se100 treatment (30.05 μg Se·g-1 and 194 ± 38 μg Se·g-1 dry mass, respectively). Larvae showed highest total length when fed Se3 rotifers, whereas flexion index was highest in larvae fed Se10. Selenium supplementation increased the gene expression of selenoproteins gpx1, msrb1, trxr2, selenom, selenop, and selenoe compared to the non-supplemented control (Se0), but only marginal differences were detected between supplementation levels. In contrast, expression of the antioxidant enzymes cat and sod1 were lowest in larvae fed Se100. To conclude, non-Se-enriched rotifers may be suboptimal for first feeding ABT larvae, which showed improved selenoprotein and antioxidant gene expression when fed a diet containing 4.42 μg Se·g-1 dry mass.

Maternal organic selenium supplementation during gestation enhances muscle fiber area and muscle fiber maturation of offspring in porcine model

BackgroundOrganic selenium supplementation during gestation improves the antioxidant status and reproductive performance of sows and increases the antioxidative capacity of the intestines of their offspring. This study was conducted to investigate the effect of maternal basel diet (control) supplemented with an organic Se, 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), or inorganic sodium selenite (Na2SeO3) during gestation on the antioxidant status and development of muscle in newborn and weaned piglets. Newborn piglets before colostrum intake and weaned piglets were selected for longissimus dorsi (LD) muscle collection and analysis.ResultsThe results showed that maternal HMSeBA supplementation increased the muscle area and content of Se in the LD muscle of newborn piglets, improved gene expression of selenoproteins, and decreased oxidative status in the LD muscle of both newborn and weaned piglets compared with the control. The expression of muscle development-related genes of newborn piglets in the HMSeBA group was lower than in the control group, whereas the expression of MRF4 in weaned piglets was higher in the HMSeBA group than in the control and Na2SeO3 groups. In addition, HMSeBA supplementation decreased the mRNA expressions of myosin heavy chains (MyHC) IIx and MyHC IIb and the percentage of MyHC IIb; increased the expression of PGC-1α in the LD muscle of newborn piglets; increased the gene expression of MyHC IIa; and decreased the protein expression of slow MyHC and the activity of malate dehydrogenase in the LD muscle of weaned piglets compared with the control group.ConclusionsMaternal HMSeBA supplementation during gestation can improve the antioxidative capacity of the muscle of their offspring and promote the maturity of muscle fibres in weaned offspring.

Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling.

The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.

Comprehensive Analysis of Expression and Prognostic Value of Selenoprotein Genes in Thyroid Cancer.

Background: Low selenium levels are associated with an increased incidence and advanced stage of thyroid cancers (THCAs). In response to changes in selenium levels, a hierarchy of selenoprotein biosynthesis allows tissue-specific fine-tuning of the 25 selenoproteins. To determine the role of individual selenoproteins on thyroid carcinogenesis, we carried out a multiomic data mining study. Methods: The expression levels of individual selenoproteins and their correlations with prognosis in THCAs were analyzed using Oncomine, GEPIA, and Kaplan-Meier plotter platforms. Co-expression analyses using the cBioportal database were carried out to identify genes that are correlated with selenoproteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments were performed for genes correlated with selenoproteins that were identified as clinically significant. Results and Discussion: DIO1, GPX3, SELENOO, SELENOP, SELENOS, and SELENOV were significantly downregulated in THCAs and were associated with poor prognoses. Biological processes including negative regulation of growth and angiogenesis were enriched in DIO1-positively and DIO1-negatively correlated genes, respectively. Many biological processes including negative regulation of growth and MAPK cascade were enriched in GPX3-positively and GPX3-negatively correlated genes, respectively. The antitumor effects of SELENOS might be attributed to their protection against endoplasmic reticulum (ER) stress. SELENOO was revealed to be correlated with ER stress, mitochondrial translation, and telomere maintenance. Biological processes of SELENOV-correlated genes were enriched in redox processes and ER calcium ion homeostasis. Moreover, cell adhesion and angiogenesis were also shown to be negatively regulated by SELENOV, providing an antimetastatic effect similar as DIO1. Conclusion: This study explored the distinct roles of the 25 selenoproteins in THCA pathogenesis, providing potential oncosuppressing effects of 6 selenoproteins.

Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model.

Simple SummaryThe present work analyzed the expression of genes involved in radiation, using an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Results showed important findings of genes involved in cancers of the breast, lung, and nervous system, and others. Most of those genes analyzed in these studies such as ATM, selenoproteins, GABA receptor, interleukins, epsin, and cathepsin inhibitors like stefins, and metallothioneins can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. In conclusion, gene signature demonstrated to be specific to cell line types, hence cell-dependency must be considered in future radiotherapy treatment planning since molecular and clinical features affect such results. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects.This study aimed to analyze the expression of genes involved in radiation, using an Affymetrix system with an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Altered expression of different molecules was detected in the non-tumorigenic Alpha3, a malignant cell line transformed only by radiation and originally derived from the parental MCF-10F human cell line; that was compared with the Alpha 5 cell line, another cell line exposed to radiation and subsequently grown in the presence 17β-estradiol. This Alpha5, a tumorigenic cell line, originated the Tumor2 cell line. It can be summarized that the Alpha 3 cell line was characterized by greater gene expression of ATM and IL7R than control, Alpha5, and Tumor2 cell lines, it presented higher selenoprotein gene expression than control and Tumor2; epsin 3 gene expression was higher than control; stefin A gene expression was higher than Alpha5; and metallothionein was higher than control and Tumor2 cell line. Therefore, radiation, independently of estrogen, induced increased ATM, IL7R, selenoprotein, GABA receptor, epsin, stefin, and metallothioneins gene expression in comparison with the control. Results showed important findings of genes involved in cancers of the breast, lung, nervous system, and others. Most genes analyzed in these studies can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. Most of all, it was revealed that in the Alpha model, a breast cancer model developed by the authors, the cell line transformed only by radiation, independently of estrogen, was characterized by greater gene expression than other cell lines. Understanding the effect of radiotherapy in different cells will help us improve the clinical outcome of radiotherapies. Thus, gene signature has been demonstrated to be specific to tumor types, hence cell-dependency must be considered in future treatment planning. Molecular and clinical features affect the results of radiotherapy. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects while providing new insights into breast cancer-related fields.

Aberrant Gene Expression of Selenoproteins in Chicken Spleen Lymphocytes Induced by Mercuric Chloride.

Mercury (Hg) is a heavy metal widely distributed in ecological environment, poisoning the immune system of humans and animals. Selenium (Se) is an essential microelement and selenoproteins involved in the procedure of Se antagonizing organ toxicity induced by heavy metals. The aim of this research was to investigate the changes of gene expression profile of selenoproteins induced by mercuric chloride (HgCl2) in chicken spleen lymphocytes. We established cytotoxicity model of chicken spleen lymphocytes by HgCl2 exposure, the messenger RNA (mRNA) expression levels of 25 selenoproteins in spleen lymphocytes were analyzed by real-time quantitative PCR (qPCR), and the gene expression pattern of selenoproteins was revealed by principal component analysis (PCA). The results showed that the mRNA expression levels of 13 selenoproteins (GPX3, GPX4, TXNRD2, TXNRD3, DIO2, SELENOS, SELENON, SELENOT, SELENOO, SELENOP, SELENOP2, MSRB1, and SEPHS2) were decreased in HgCl2 treatment group, and there was strong positive correlation between these selenoproteins and component 1 as well as component 2 of the PCA. At the same time, the protein expression levels of GPX4, TXNRD1, TXNRD2, SELENOM, SELENOS, and SELENON were detected by Western blotting, which were consistent with the changes of gene expression. The results showed that the expression levels of selenoproteins were aberrant in response to HgCl2 toxicity. The information presented in this study provided clues for further research on the interaction between HgCl2 and selenoproteins, and the possible mechanism of immune organ toxicity induced by HgCl2.

Dysregulation of Transcription Profile of Selenoprotein in Patients with Kashin-Beck Disease and Its Effect on Se Deficiency-Induced Chondrocyte Apoptosis.

Kashin-Beck disease (KBD) is a chronic, degenerative osteoarthropathy related to selenium (Se) deficiency. Se participates in the synthesis of selenoprotein in the form of selenocysteine. In total, 25 selenoproteins, encoded by 25 genes, are currently found in humans; however, the effects of selenoprotein genes on chondrocyte apoptosis, particularly in apoptosis-related genes, remain poorly elucidated. Therefore, in the current study, the expression of selenoprotein genes and apoptosis-related genes were determined by RT-qPCR in patients and chondrocytes and the correlations between them were analyzed using Pearson and Spearman's rank correlation, and the chondrocyte apoptosis rate was detected by Annexin V-FITC/PI. The results showed that the mRNA levels of 17 selenoprotein genes were downregulated, whereas two genes were upregulated in patients with KBD. The BAX/BCL2 ratio and the mRNA levels of BAX and P53 were increased, but the mRNA levels of BCL2 and NF-κB p65 were decreasedin patients with KBD. The mRNA levels of GPX2, GPX3, DIO1, TXNRD1, TXNRD3, and SPS2 were most closely associated with apoptosis-related genes in patients with KBD. Moreover, in the Se deficiency group, the mRNA levels of GPX3, DIO1, and TXNRD1 were downregulated and GPX activity was decreased, but the late apoptosis rate, the mRNA levels of BAX and P53, and the BAX/BCL2 ratio were increased; the opposite trend was observed in the Se supplement group. Collectively, these results indicate that selenoprotein transcription profile is dysregulated in patients with KBD. Furthermore, the expression of GPX3, DIO1, and TXNRD1 genes might be involved in the development of chondrocyte apoptosis by affecting antioxidant capacity.

Genetically determined variations of selenoprotein P are associated with antioxidant, muscular, and lipid biomarkers in response to Brazil nut consumption by patients using statins

Several single nucleotide polymorphisms (SNPs) could indirectly, as well directly, influence metabolic parameters related to health effects in response to selenium (Se)supplementation. This study aimed to investigate whether the selenoprotein SNPs were associated with the response of Se status biomarkers to the Brazil nut consumption in patients using statins and if the variation in Se homoeostasis could affect antioxidant protection, lipid profile, muscle homoeostasis and selenoproteins mRNA. The study was performed in the Ribeirão Preto Medical School University Hospital. Thirty-two patients using statins received one unit of Brazil nut daily for 3 months. Body composition, blood Se concentrations, erythrocyte glutathione peroxidase (GPX) activity, total cholesterol, low-density lipoprotein(LDL), high-density lipoprotein (HDL), triacylglycerol (TAG), creatine kinase (CK) activity and gene expression of GPX1 and selenoprotein P (SELENOP) were evaluated before and after Brazil nut consumption. The volunteers were genotyped for SNP in GPX1 (rs1050450) and SELENOP (rs3877899 and rs7579). SNPs in selenoproteins were not associated with plasma and erythrocyte Se, but SNPs in SELENOP influenced the response of erythrocyte GPX activity and CK activity, TAG and LDL after Brazil nut consumption. Also, Brazil nut consumption increased GPX1 mRNA expression only in subjects with rs1050450 CC genotype. SELENOP mRNA expression was significantly lower in subjects with rs7579 GG genotype before and after the intervention. Thus, SNP in SELENOP could be associated with interindividual differences in Se homeostasis after Brazil nut consumption, emphasising the involvement of genetic variability in response to Se consumption towards health maintenance and disease prevention.

Activation of Nrf2 by Electrophiles Is Largely Independent of the Selenium Status of HepG2 Cells

Selenoenzymes, whose activity depends on adequate selenium (Se) supply, and phase II enzymes, encoded by target genes of nuclear factor erythroid 2-related factor 2 (Nrf2), take part in governing cellular redox homeostasis. Their interplay is still not entirely understood. Here, we exposed HepG2 hepatoma cells cultured under Se-deficient, Se-adequate, or Se-supranutritional conditions to the Nrf2 activators sulforaphane, cardamonin, or diethyl maleate. Nrf2 protein levels and intracellular localization were determined by immunoblotting, and mRNA levels of Nrf2 target genes and selenoproteins were assessed by qRT-PCR. Exposure to electrophiles resulted in rapid induction of Nrf2 and its enrichment in the nucleus, independent of the cellular Se status. All three electrophilic compounds caused an enhanced expression of Nrf2 target genes, although with differences regarding extent and time course of their induction. Whereas Se status did not significantly affect mRNA levels of the Nrf2 target genes, gene expression of selenoproteins with a low position in the cellular “selenoprotein hierarchy”, such as glutathione peroxidase 1 (GPX1) or selenoprotein W (SELENOW), was elevated under Se-supplemented conditions, as compared to cells held in Se-deficient media. In conclusion, no major effect of Se status on Nrf2 signalling was observed in HepG2 cells.

Selenocysteine insertion sequence binding protein 2 (Sbp2) in the sex-specific regulation of selenoprotein gene expression in mouse pancreatic islets

Selenoproteins are a group of selenocysteine-containing proteins with major roles in cellular antioxidant defense and thyroid hormone metabolism. Selenoprotein expression is determined by hierarchical mechanisms that result in tissue-specific levels. Current data inadequately explain the abundance of various selenoproteins under normal and pathological conditions, including in pancreatic β-cells. Selenocysteine insertion sequence binding protein 2 (SBP2) is a critical protein in selenoprotein translation that also plays an essential role in stabilizing selenoprotein transcripts by antagonizing nonsense-mediated decay (NMD). Importantly, dysfunctional SBP2 is associated with endocrine disorders in humans. Here we describe the impact of induced Sbp2 deficiency in pancreatic β-cells on selenoprotein transcript profiles in the pancreatic islets of C57BL/6J mice. Sex differences were noted in control mice, in which female islets showed 5 selenoproteins decreased and one increased versus male islets. Induced Sbp2 deficiency in pancreatic β-cells altered expression of only 3 selenoprotein transcripts in male islets, whereas 14 transcripts were reduced in female islets. In all cases, decreased transcription was observed in genes known to be regulated by NMD. The differential impact of Sbp2 deletion on selenoprotein transcription between sexes suggests sex-specific hierarchical mechanisms of selenoprotein expression that may influence islet biology and consequentially metabolic disease risk.

Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer.

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.

Response of selenoproteins gene expression profile to mercuric chloride exposure in chicken kidney

Kidney is a primary target organ for mercuric chloride (HgCl2) toxicity. Selenium (Se) can exert antagonistic effect on heavy metals-induced organ toxicity by regulating the expression of selenoproteins. The objective of this study was to investigate the effect of HgCl2 on the gene expression of selenoproteins in chicken kidney. Sixty male Hyline brown chickens were randomly and evenly divided into two groups. After acclimatization for one week, chickens were provided with the standard diet as well as non-treated water (CON group), and standard diet as well as HgCl2-treated water (250 ppm, HgCl2 group). After seven weeks, kidney tissues were collected to examine the mRNA expression levels of 25 selenoproteins genes and protein expression levels of 4 selenoproteins. Moreover, correlation analysis and principal component analysis (PCA) were used to analyze the expression patterns of 25 selenoproteins. The results showed that HgCl2 exposure significantly decreased the mRNA expression of Glutathione peroxidase 1 (GPX1), GPX4, Thioredoxin reductase 2 (TXNRD2), Iodothyronine deiodinase 1 (DIO1), Methionine-Rsulfoxide reductase 1 (SELR), 15-kDa selenoprotein (SEP15), selenoprotein I (SELI), SELK, SELM, SELN, SELP, SELS, SELT, SELW, and SEPHS2. Meanwhile, HgCl2 exposure significantly increased the mRNA expression of GPX3, TXNRD1, and SELU. Western blot analysis showed that the expression levels of GPX3, TXNRD1, SELK, and SELN were concordant with these mRNA expression levels. Analysis results of selenoproteins expression patterns showed that HgCl2-induced the main disorder expression of selenoproteins with antioxidant activity and endoplasmic reticulum resident selenoproteins. In conclusion, selenoproteins respond to HgCl2 exposure in a characteristic manner in chicken kidney.

Effect of Statin Treatment on Obese Mice Lacking Selenocysteine Lyase

Abstract Objectives Americans are a selenium-replete population with high use of statins, a drug commonly prescribed to ameliorate hypercholesterolemia. Statins act by inhibiting the first step of cholesterol biosynthesis in the liver, the mevalonate pathway. This pathway is also important for the maturation of the selenocysteine tRNA, responsible for the expression of selenoproteins. Selenoprotein deficits were suggested as responsible for side effects of statins, such as increased oxidative stress leading to muscle cramps and myopathies. Selenium for selenoprotein synthesis can be provided by diet or by the actions of the selenium recycling enzyme selenocysteine lyase (Scly). Our objective was to investigate the effects of the use of statins in an animal model lacking the enzyme Scly and fed a high-fat, Se-supplemented diet. Methods Age-matched homozygous littermates wild-type C57BL/6 N (WT) and Scly knockout (Scly KO) mice were fed a high-fat diet containing a 1 ppm blend of selenite plus selenomethionine, and were daily treated with simvastatin (5 mg/kg of body weight) for 21 days. We analyzed serum cholesterol levels, oxidative stress and creatine kinase (CK) activity, and liver and skeletal muscle gene expression of selenoproteins and enzymes involved in creatine metabolism. Results Obese Scly KO mice had a sex-dependent response statin treatment. While female Scly KO mice improved their body weight after statin treatment, male Scly KO mice further gained weight. Statin treatment improved serum oxidative stress in the Scly KO mice, despite sharp elevation of CK activity. Statin treatment did not affect hepatic selenoprotein gene expression of Scly KO mice, but impaired glutathione peroxidase 1 expression in the muscle of male Scly KO mice, while enhancing it in females. Conclusions Responses to statin treatment in Scly KO mice fed a high-fat, Se-supplemented diet vary according to sex, benefiting more female than male mice, and are mostly independent of selenoprotein expression. Funding Sources National Institutes of Health (NIH) grants U54MD007601 Ola Hawaii (subproject 5544) and R01DK47320, and Fundação de Amparo à Pesquisa do Estado de São Paulo fellowship 2018/0,9478–4. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Nano-selenium Supplementation Increases Selenoprotein (Sel) Gene Expression Profiles and Milk Selenium Concentration in Lactating Dairy Cows

Supplementation with selenium is common for dairy cows, but the importance of selenium source is not clear. This study aimed to compare nano-selenium (Nano-Se) and sodium selenite supplements for dairy cows on lactation performance, milk Se levels and selenoprotein (Sel) gene expression. Twelve multiparous Holstein cows were randomly divided into two groups: a control group fed a basal diet plus 0.30 mg Se/kg of DM as sodium selenite or Nano-Se for 30 days. Dry matter intake, milk yield and composition were not affected by dietary Se source (P > 0.05); however, the milk total Se levels and milk glutathione peroxidase (GSH-Px) activities were higher with Nano-Se supplementation than sodium selenite (P < 0.05). At the end of the experiment, Nano-Se supplementation significantly increased plasma Se levels and GSH-Px activity, compared with the sodium selenite supplement. The mRNA expression levels of glutathione peroxidase 1, 2 and 4; thioredoxin reductase 2 and 3; and selenoproteins W, T, K and F were markedly upregulated (P < 0.05) in the mammary gland of the Nano-Se group. Thus, the source of selenium plays an important role in the antioxidant status and in particular the Sel gene expression in the mammary glands of dairy cows, both being stimulated by nano sources.

Targeted Metabolomics Analysis Reveals that Dietary Supranutritional Selenium Regulates Sugar and Acylcarnitine Metabolism Homeostasis in Pig Liver

The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear. Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs. Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0±3.3kg) were fed SeMet adequate (Se-A, 0.25mg Se/kg) or SeMet supranutritional (Se-S, 2.5mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed. The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P <0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P <0.05), but expression of most selenoprotein genes and selenoenzyme activity did not differ between the 2 groups. Seven of 27 targeted sugar metabolites and 4 of 21 acylcarnitine metabolites significantly changed in response to high SeMet (P <0.05). High SeMet supplementation significantly upregulated phosphoenolpyruvate carboxy kinase (PEPCK) activity by 64.4% and decreased hexokinase and succinate dehydrogenase (SDH) activity by 46.5-56.7% (P <0.05). The relative contents of glucose, dihydroxyacetone phosphate, α-ketoglutarate, fumarate, malate, erythrose-4-phosphate, and sedoheptulose-7-phosphate in the Se-S group were 21.1-360% greater than those in the Se-A group (P <0.05). The expression of fatty acid synthase (FASN) and the relative contents of carnitine, hexanoyl-carnitine, decanoyl-carnitine, and tetradecanoyl-carnitine in the Se-S group were 35-97% higher than those in the Se-A group (P <0.05). Dietary high SeMet-induced hyperglycemia and hyperinsulinemia were associated with suppression of sugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes.

Analysis of Selenoprotein Expression in Response to Dietary Selenium Deficiency During Pregnancy Indicates Tissue Specific Differential Expression in Mothers and Sex Specific Changes in the Fetus and Offspring.

The human selenoproteome is comprised of ~25 genes, which incorporate selenium, in the form of selenocysteine, into their structure. Since it is well known that selenium is important to maternal health and foetal development during pregnancy, this study aimed at defining the impact of selenium deficiency on maternal, placental, foetal and offspring selenoprotein gene expression. Female C57BL/6 mice were randomly allocated to control (>190 μg/kg) or low selenium (<50 μg/kg) diets four weeks prior to mating and throughout gestation. At embryonic day (E)18.5, pregnant mice were sacrificed followed by collection of maternal and foetal tissues. A subset of mice littered down, and offspring were monitored from postnatal day (PN) 8, weaned at PN24 and sacrificed at PN180, followed by tissue collection. Following RNA extraction, the expression of 14 selenoproteins was assessed with qPCR in liver, kidneys, muscle and placenta. Selenium deficiency downregulated expression (Ptrt < 0.05) of many selenoproteins in maternal tissues and the placenta. However, foetal selenoprotein expression was upregulated (Ptrt < 0.05) in all tissues, especially the kidneys. This was not reflected at PN180; however, a sexually dimorphic relationship in selenoprotein expression was observed in offspring. This study demonstrates the selenoproteome is sensitive to dietary selenium levels, which may be exacerbated by pregnancy. We concluded that transcriptional regulation of selenoproteins is complex and multifaceted, with expression exhibiting tissue-, age- and sex-specificities.