Search Results (14)

This study investigated the protective effects of high selenomethionine (SeMet) supplementation on liver injury caused by oxidative stress in piglets and explored the underlying mechanisms. A total of 18 piglets were randomly assigned to three groups, with six replicates in each group. The control (CON) and diquat (DQ) groups were fed a basal diet supplemented with 0.3 mg Se/kg Se, while the SeMet group received a basal diet supplemented with 1.0 mg Se/kg. The results indicated that SeMet supplementation significantly improved growth performance and increased the serum and liver activities of antioxidant enzymes. Additionally, it reduced the serum and liver levels of malondialdehyde and protein carbonyls in piglets exposed to DQ. Selenoprotein transcriptome analysis showed that the mRNA levels of five selenoprotein genes (GPX1/3, DIO2, and SELENOF/M/W) were significantly upregulated by dietary SeMet supplementation in the liver of DQ-challenged piglets. Proteomic analysis revealed that a total of 3614 proteins were identified in the liver of piglets. Among them, 85 differentially expressed proteins (DEPs) were identified between the CON and DQ groups, 58 DEPs were observed between the DQ and SeMet groups, and 113 DEPs were identified between the CON and SeMet groups. KEGG analysis indicated that most of the DEPs observed among the three groups were involved in fatty acid metabolism, glycolysis/gluconeogenesis, and the PPAR signaling pathway. Together, these results indicate that dietary supplementation with supernutritional SeMet alleviates the negative effects of the DQ challenge on growth performance and liver injury in piglets. This effect is associated with increased antioxidant capacity, enhanced expression of certain selenoprotein genes, and the regulation of fatty acid metabolism. Full article

Selenoproteins contain selenium (Se), which is included in the 21st proteinogenic amino acid selenocysteine (Sec). Selenium (Se) is an essential trace element that exerts its biological actions mainly through selenoproteins. Selenoproteins have crucial roles in maintaining healthy brain activity. At the same time, brain-function-associated selenoproteins may also be involved in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The selenoproteins GPx4 (glutathione peroxidase 4), GPx1 (glutathione peroxidase 1), SELENOP (selenoprotein P), SELENOK (selenoprotein K), SELENOS (selenoprotein S), SELENOW (selenoprotein W), and SELENOT (selenoprotein T) are highly expressed, specifically in AD-related brain regions being closely correlated to brain function. Only a few selenoproteins, mentioned above (especially SELENOP), can bind transition and heavy metals. Metal ion homeostasis accomplishes the vital physiological function of the brain. Dyshomeostasis of these metals induces and entertains neurodegenerative diseases. In this review, we described some of the proposed and established mechanisms underlying the actions and properties of the above-mentioned selenoproteins having the characteristic feature of binding transition or heavy metals. Full article

Obstructive sleep apnoea (OSA) involves impaired upper airway muscle function and is linked to several pathologies including systemic hypertension, daytime somnolence and cognitive decline. Selenium is an essential micronutrient that exerts many of its effects through selenoproteins. Evidence indicates that either deficient or excessive dietary selenium intake can result in impaired muscle function, termed nutritional myopathy. To investigate the effects of selenium on an upper airway muscle, the sternohyoid, rats were fed on diets containing deficient, normal (0.5 ppm sodium selenite) or excessive (5 ppm selenite) selenium for a period of two weeks. Sternohyoid contractile function was assessed ex vivo. Serum selenium levels and activity of the glutathione antioxidant system were determined by biochemical assays. The abundance of three key muscle selenoproteins (selenoproteins -N, -S and -W (SELENON, SELENOS and SELENOW)) in sternohyoid muscle were quantified by immunoblotting. Levels of these selenoproteins were also compared between rats exposed to chronic intermittent hypoxia, a model of OSA, and sham treated animals. Although having no detectable effect on selected organ masses and whole-body weight, either selenium-deficient or -excessive diets severely impaired sternohyoid contractile function. These changes did not involve altered fibre size distribution. These dietary interventions resulted in corresponding changes in serum selenium concentrations but did not alter the activity of glutathione-dependent antioxidant systems in sternohyoid muscle. Excess dietary selenium increased the abundance of SELENOW protein in sternohyoid muscles but had no effect on SELENON or SELENOS. In contrast, chronic intermittent hypoxia increased SELENON, decreased SELENOW and had no significant effect on SELENOS in sternohyoid muscle. These findings indicate that two-week exposure to selenium-deficient or -excessive diets drastically impaired upper airway muscle function. In the sternohyoid, SELENON, SELENOS and SELENOW proteins show distinct alterations in level following exposure to different dietary selenium intakes, or to chronic intermittent hypoxia. Understanding how alterations in Se and selenoproteins impact sternohyoid muscle function has the potential to be translated into new therapies for prevention or treatment of OSA. Full article

Selenium (Se) is an indispensable trace element with versatile functions in antioxidant defense in poultry. In our previous study, we synthesized a novel type of biogenic selenium nanoparticle based on alginate oligosaccharides (SeNPs-AOS), and found that the particles are sized around 80 nm with an 8% Se content, and the dietary addition of 5 mg/kg of SeNPs-AOS could effectively alleviate the deleterious effects of heat stress (HS) in broilers, but it is still unclear whether SeNPs-AOS can improve the meat quality. Therefore, the aim of this study was to evaluate the protective effects of SeNPs-AOS on breast meat quality in heat-stressed broilers, and explore the relevant mechanisms. Birds at the age of 21 days were randomly divided into four groups with six replicates per group (eight broilers per replicate) according to a 2 × 2 experimental design, using HS (33 ± 2 °C, 10 h/day vs. thermoneutral, TN, under 23 ± 1.5 °C) and SeNPs-AOS (5 mg/kg feed vs. no inclusion) as variables. The results showed that dietary SeNPs-AOS decreased the cooking loss (p < 0.05), freezing loss (p < 0.001), and shear force (p < 0.01) of breast muscle in heat-stressed broilers. The non-targeted metabolomics analysis of the breast muscle identified 78 differential metabolites between the HS and HS + SeNPs-AOS groups, mainly enriched in the arginine and proline metabolism, β-alanine metabolism, D-arginine and D-ornithine metabolism, pantothenate, and CoA biosynthesis pathways (p < 0.05). Meanwhile, supplementation with SeNPs-AOS increased the levels of the total antioxidant capacity (T-AOC), the activities of catalase (CAT) and glutathione peroxidase (GSH-Px), and decreased the content of malondialdehyde (MDA) in the breast muscle (p < 0.05) in broilers under HS exposure. Additionally, SeNPs-AOS upregulated the mRNA expression of CAT, GPX1, GPX3, heme oxygenase-1 (HO-1), masculoaponeurotic fibrosarcoma G (MafG), MafK, selenoprotein W (SELENOW), SELENOK, ferritin heavy polypeptide-1 (FTH1), Ferroportin 1 (Fpn1), and nuclear factor erythroid 2-related factor 2 (Nrf2) (p < 0.05), while it downregulated Kelch-like ECH-associated pro-36 tein 1 (Keap1) and prostaglandin-endoperoxide Synthase 2 (PTGS2) expression (p < 0.05) in broilers under HS. These findings demonstrated that the dietary addition of SeNPs-AOS mitigated HS-induced oxidative damage and metabolite changes in the breast muscle of broilers, which may be related to the regulation of the Nrf2 signaling pathway and selenoprotein synthesis. In addition, SeNPs-AOS upregulated the breast muscle gene expression of anti-ferroptosis-related molecules in broilers under HS, suggesting that SeNPs-AOS can be used as novel Se supplements against HS in broilers. Full article

Selenium (Se) is a metalloid that is recognized as one of the vital trace elements in our body and plays multiple biological roles, largely mediated by proteins containing selenium—selenoproteins. Selenoproteins mainly have oxidoreductase functions but are also involved in many different molecular signaling pathways, physiological roles, and complex pathogenic processes (including, for example, teratogenesis, neurodegenerative, immuno-inflammatory, and obesity development). All of the selenoproteins contain one selenocysteine (Sec) residue, with only one notable exception, the selenoprotein P (SELENOP), which has 10 Sec residues. Although these mechanisms have been studied intensely and in detail, the characteristics and functions of many selenoproteins remain unknown. This review is dedicated to the recent data describing the identity and the functions of several selenoproteins that are less known than glutathione peroxidases (Gpxs), iodothyronine deiodinases (DIO), thioredoxin reductases (TRxRs), and methionine sulfoxide reductases (Msrs) and which are named after alphabetical letters (i.e., F, H, I, K, M, N, O, P, R, S, T, V, W). These “alphabet” selenoproteins are involved in a wide range of physiological and pathogenetic processes such as antioxidant defense, anti-inflammation, anti-apoptosis, regulation of immune response, regulation of oxidative stress, endoplasmic reticulum (ER) stress, immune and inflammatory response, and toxin antagonism. In selenium deficiency, the “alphabet” selenoproteins are affected hierarchically, both with respect to the particular selenoprotein and the tissue of expression, as the brain or endocrine glands are hardly affected by Se deficiency due to their equipment with LRP2 or LRP8. Full article

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4–6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined. Full article

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα⁺ macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1. Full article

The objective of this study is to observe the effect of high selenium on the antioxidant and immune functions of growing goats based on transcriptome sequencing. Eighteen goats were randomly divided into three groups: (1) the control (CON) group was fed a basal diet, and (2) the treatment 1 group (LS) and treatment 2 group (HS) were fed a basal diet with 2.4 and 4.8 mg/kg selenium-yeast (SY), respectively. The results indicate that HS treatment significantly (p < 0.05) increased the apparent digestibility of either extract and significantly increased (p < 0.05) total antioxidant capacity, whereas it significantly (p < 0.05) decreased plasma aspartate aminotransferase and malondialdehyde relative to the control group. The LS treatment had significantly (p < 0.05) increased glutathione S-transferase and catalase compared to CON. A total of 532 differentially expressed genes (DEGs) between the CON and HS were obtained using transcriptome sequencing. Kyoto Encyclopedia of Genes and Genomes analysis identified upregulated (p < 0.05) DEGs mainly related to vascular smooth muscle contraction, alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, the VEGF signalling pathway, and proteoglycans in cancer; downregulated (p < 0.05) DEGs mainly related to the NOD-like receptor signalling pathway, influenza A, cytokine-cytokine receptor interaction, haematopoietic cell lineage, and African trypanosomiasis. Ontology analyses of the top genes show that the identified DEGs are mainly involved in the regulation of granulocyte macrophage colony-stimulating factor production for biological processes, the external side of the plasma membrane for cellular components, and carbohydrate derivative binding for molecular functions. Seven genes are considered potential candidate genes for regulating antioxidant activity, including selenoprotein W, 1, glutathione peroxidase 1, glutathione S-transferase A1, tumour necrosis factor, tumour necrosis factor superfamily member 10, tumour necrosis factor superfamily member 8, and tumour necrosis factor superfamily member 13b. The experimental observations indicate that dietary supplementation with 4.8 mg/kg SY can enhance antioxidant and immune functions by improving muscle immunity, reducing the concentrations of inflammatory molecules, and modulating antioxidant and inflammatory signalling pathways in growing goats. Full article

The essential trace element selenium plays an important role in maintaining brain function. Selenoprotein W (SELENOW), the smallest selenoprotein that has been identified in mammals, is sensitive to selenium levels and abundantly expressed in the brain. However, its biological role in the brain remains to be clarified. Here, we studied the morphological and functional changes in the brain caused by SELENOW deficiency using its gene knockout (KO) mouse models. Histomorphological alterations of the amygdala and hippocampus, specifically in the female SELENOW KO mice, were observed, ultimately resulting in less anxiety-like behavior and impaired contextual fear memory. Fear conditioning (FC) provokes rapidly intricate responses involving neuroplasticity and oligodendrogenesis. During this process, the females generally show stronger contextual FC than males. To characterize the effect of SELENOW deletion on FC, specifically in the female mice, a Tandem mass tag (TMT)-based comparative proteomic approach was applied. Notably, compared to the wildtype (WT) no shock (NS) mice, the female SELENOW KO NS mice shared lots of common differentially expressed proteins (DEPs) with the WT FC mice in the hippocampus, enriched in the biological process of ensheathment and oligodendrocyte differentiation. Immunostaining and Western blotting analyses further confirmed the proteomic results. Our work may provide a holistic perspective of gender-specific SELENOW function in the brain and highlighted its role in oligodendrogenesis during fear memory. Full article

Selenoprotein W (SELENOW) is a 9.6 kDa protein containing selenocysteine (Sec, U) in a conserved Cys-X-X-Sec (CXXU) motif. Previously, we reported that SELENOW regulates various cellular processes by interacting with 14-3-3β at the U of the CXXU motif. Thioredoxin (Trx) is a small protein that plays a key role in the cellular redox regulatory system. The CXXC motif of Trx is critical for redox regulation. Recently, an interaction between Trx1 and 14-3-3 has been predicted. However, the binding mechanism and its biological effects remain unknown. In this study, we found that Trx1 interacted with 14-3-3β at the Cys32 residue in the CXXC motif, and SELENOW and Trx1 were bound at Cys191 residue of 14-3-3β. In vitro binding assays showed that SELENOW and Trx1 competed for interaction with 14-3-3β. Compared to control cells, Trx1-deficient cells and SELENOW-deficient cells showed increased levels of both the subG1 population and poly (ADP-ribose) polymerase (PARP) cleavage by etoposide treatment. Moreover, Akt phosphorylation of Ser473 was reduced in Trx1-deficient cells and was recovered by overexpression of SELENOW. These results indicate that SELENOW can protect Trx1-deficient cells from etoposide-induced cell death through its interaction with 14-3-3β. Full article

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. Full article

Selenium is a vital trace element present as selenocysteine (Sec) in proteins that are, thus, known as selenoproteins. Humans have 25 selenoproteins, most of which are functionally characterized as oxidoreductases, where the Sec residue plays a catalytic role in redox regulation and antioxidant activity. Glutathione peroxidase plays a pivotal role in scavenging and inactivating hydrogen and lipid peroxides, whereas thioredoxin reductase reduces oxidized thioredoxins as well as non-disulfide substrates, such as lipid hydroperoxides and hydrogen peroxide. Selenoprotein R protects the cell against oxidative damage by reducing methionine-R-sulfoxide back to methionine. Selenoprotein O regulates redox homeostasis with catalytic activity of protein AMPylation. Moreover, endoplasmic reticulum (ER) membrane selenoproteins (SelI, K, N, S, and Sel15) are involved in ER membrane stress regulation. Selenoproteins containing the CXXU motif (SelH, M, T, V, and W) are putative oxidoreductases that participate in various cellular processes depending on redox regulation. Herein, we review the recent studies on the role of selenoproteins in redox regulation and their physiological functions in humans, as well as their role in various diseases. Full article

To evaluate the effects of dietary Se deficiency and excess on the mRNA levels of selenoproteins in pig spleen tissues, 20 healthy uncastrated boars (Duroc × Landrace × Yorkshire, 10 ± 0.72 kg) were randomly divided into four groups (5 pigs per group). The pigs were fed a Se deficient corn-soybean basal feed (Se content <0.03 mg/kg) or basal feed with added sodium selenite at 0.3, 1.0, or 3.0 mg Se/kg diet, respectively. The experiment lasted 16 weeks. The spleen tissue was collected to examine the mRNA expression levels of 24 selenoprotein genes at the end of the study. Compared with pigs in other groups, those fed with the 1.0 mg Se/kg diet had higher mRNA levels of glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), deiodinase type II (Dio2), thioredoxin reductase 3 (Txnrd3), selenoprotein H (Selh), selenoprotein N, 1 (Sepn1), selenoprotein P1 (Sepp1), and selenoprotein V (Selv) in the spleen (p < 0.05). Dietary Se deficiency resulted in lower mRNA levels of Gpx1, Gpx2, glutathione peroxidase 3 (Gpx3), Dio2, thioredoxin reductase 2 (Txnrd2), Txnrd3, Selh, selenoprotein I (Seli), selenoprotein K (Selk), selenoprotein M (Selm), Sepn1, Sepp1, and Selv in the spleen than the other three groups. Dietary Se levels did not affect the mRNA levels of glutathione peroxidase 4 (Gpx4), deiodinase type I (Dio1), deiodinase type III (Dio3), selenophosphate synthetase 2 (Sephs2), thioredoxin reductase 1 (Txnrd1), selenoprotein O (Selo), selenoprotein S (Sels), selenoprotein W (Selw), selenoprotein X (Selx), and selenoprotein 15 (Sel15) in the spleen (p > 0.05). Dietary Se levels can affect the transcription levels of 14 selenoprotein genes in the spleen of pigs. Full article

Selenium (Se) deficiency is associated with the occurrence of many diseases. However, excessive Se supplementation, especially with inorganic Se, can result in toxicity. Selenoproteins are the major forms of Se in vivo to exert its biological function. Expression of those selenoproteins, especially with the application of a newly developed system, is thus very important for studying the mechanism of Se in nutrition. The use of Chlamydomonas reinhardtii (C. reinhardtii) as a biological vector to express an heterogeneous protein is still at the initial stages of development. In order to investigate the possibility of using this system to express selenoproteins, human 15-KDa selenoprotein (Sep15), a small but widely distributed selenoprotein in mammals, was chosen for the expression platform test. Apart from the wild-type human Sep15 gene fragment, two Sep15 recombinants were constructed containing Sep15 open reading frame (ORF) and the selenocysteine insertion sequence (SECIS) element from either human Sep15 or C. reinhardtii selenoprotein W1, a highly expressed selenoprotein in this alga. Those Sep15-containing plasmids were transformed into C. reinhardtii CC-849 cells. Results showed that Sep15 fragments were successfully inserted into the nuclear genome and expressed Sep15 protein in the cells. The transgenic and wild-type algae demonstrated similar growth curves in low Se culture medium. To our knowledge, this is the first report on expressing human selenoprotein in green alga. Full article