Characterization and expression analysis of seven selenoprotein genes in yellow catfish Pelteobagrus fulvidraco to dietary selenium levels

BackgroundSelenium (Se) appears in the selenoproteins in the form of selenocysteine (Sec) and is important for the growth and development of vertebrates. The present study characterized seven selenoproteins, consisting of the GPX1, GPX3, GPX4, SELENOW, SELENOP, TXNRD2 and TXNRD3 cDNAs in various tissues of yellow catfish, explored their regulation to dietary Se addition.Methods3′ and 5′ RACE PCR were used to clone full-length cDNA sequences of seven selenoprotein genes (GPX1, GPX3, GPX4, SELENOW, SELENOP, TXNRD2 and TXNRD3). Their molecular characterizations were analyzed, including conservative motifs and the SECIS elements. The phylogenetic trees were generated through neighbor-joining (NJ) method with MEGA 6.0 with 1000 bootstrap replications. Quantitative real-time PCR was used to explore their mRNA tissue distribution in the heart, anterior intestine, dorsal muscle, head kidney, gill, liver, brain, spleen and mesenteric fat. Yellow catfish (mixed sex) were fed diets with dietary Se contents at 0.03 (low Se), 0.25 (adequate Se) and 6.39 (high Se) mg Se/kg, respectively, for 12 weeks, and their spleen, kidney, testis and brain were used for the determination of the mRNA levels of the seven selenoproteins.ResultsThe seven selenoproteins had similar domains to their corresponding members of other vertebrates. They were widely expressed in nine tissues, including heart, liver, brain, spleen, head kidney, dorsal muscle, mesenteric fat, anterior intestine and gill, but showed tissue-dependent expression patterns. Dietary Se addition affected the expression of the seven genes in spleen, kidney, testis and brain tissues of yellow catfish.ConclusionTaken together, our study demonstrated the characterization, expression and regulation of seven selenoproteins, which increased our understanding of the biological functions of Se and selenoproteins in fish.     

Effects of Dietary Selenium Deficiency on mRNA Levels of Twenty-One Selenoprotein Genes in the Liver of Layer Chicken

Selenium (Se) is an essential trace element in many life forms due to its occurrence as selenocysteine (Sec) residue in selenoproteins. However, little is known about the expression pattern of selenoproteins in the liver of layer chicken. To investigate the effects of Se deficiency on the mRNA expressions of selenoproteins in the liver tissue of layer chickens, 1-day-old layer chickens were randomly allocated into two groups (n?=?120/group). The Se-deficient group (?Se) was fed a Se-deficient corn–soy basal diet; the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.15 mg/kg (sodium selenite). The liver tissue was collected and examined for mRNA levels of 21 selenoprotein genes at 15, 25, 35, 45, 55, and 65 days old. The data indicated that the mRNA expressions of Gpx1, Gpx2, Gpx3, Gpx4, Sepn1, Sepp1, Selo, Sepx1, Selu, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, SPS2, Selm, SelPb, Sep15, and Sels were decreased (p?<?0.05), but not the levels of Dio3 and Seli (p?>?0.05). The results showed that the mRNA levels of 19 selenoprotein (except Seli and Dio3) genes in the layer chicken liver were regulated by diet Se level. The present study provided some compensated data about the roles of Se in the regulation of selenoproteins.     

Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals

Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain.     

Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury

Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed selenoproteins. The selenoprotein family is small but diverse and includes key proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how selenoproteins are affected in this interaction. In this study we explored how Se and MeHg interact to affect the mRNA expression of selenoprotein genes in whole zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed MeHg with or without elevated Se in a 2×2 factorial design. The embryo mRNA levels of 30 selenoprotein genes were then measured. These genes cover most of the selenoprotein families, including members of the glutathione peroxidase (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide reductase families, along with selenophosphate synthetase 2 and selenoproteins H, J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor activity were also measured. We found that around one-quarter of the selenoprotein genes were downregulated by elevated MeHg. These downregulated genes were dominated by selenoproteins from antioxidant pathways that are also susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX activity and induced larval hypoactivity. Elevated Se partially prevented MeHg-induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval locomotor activity. Overall, the MeHg-induced downregulation and subsequent rescue by elevated Se levels of selenogenes regulated by Se status suggest that Se deficiency is a contributing factor to MeHg toxicity.     

Selenoproteins protect against avian nutritional muscular dystrophy by metabolizing peroxides and regulating redox/apoptotic signaling

Nutritional muscular dystrophy (NMD) of chicks is induced by dietary selenium (Se)/vitamin E (Vit. E) deficiencies and may be associated with oxidative cell damage. To reveal the underlying mechanisms related to the presumed oxidative cell damage, we fed four groups of 1-day-old broiler chicks (n = 40/group) with a basal diet (BD; 10 μg Se/kg; no Vit. E added, −Se −Vit. E) or the BD plus all-rac-α-tocopheryl acetate at 50 mg/kg (−Se +Vit. E), Se (as sodium selenite) at 0.3 mg/kg (+Se −Vit. E), or both of these nutrients (+Se +Vit. E) for 6 weeks. High incidences of NMD (93%) and mortality (36%) of the chicks were induced by the BD, starting at week 3. Dietary Se deficiency alone also induced muscle fiber rupture and coagulation necrosis in the pectoral muscle of chicks at week 3 and thereafter, with increased (P < 0.05) malondialdehyde, decreased (P < 0.05) total antioxidant capacity, and diminished (P < 0.05) glutathione peroxidase activities in the muscle. To link these oxidative damages of the muscle cells to the Se-deficiency-induced NMD, we first determined gene expression of the potential 26 selenoproteins in the muscle of the chicks at week 2 before the onset of symptoms. Compared with the +Se chicks, the −Se chicks had lower (P < 0.05) muscle mRNA levels of Gpx1, Gpx3, Gpx4, Sepp1, Selo, Selk, Selu, Selh, Selm, Sepw1, and Sep15. The −Se chicks also had decreased (P < 0.05) production of 6 selenoproteins (long-form selenoprotein P (SelP-L), GPx1, GPx4, Sep15, SelW, and SelN), but increased levels (P < 0.05) of the short-form selenoprotein P in muscle at weeks 2 and 4. Dietary Se deficiency elevated (P < 0.05) muscle p53, cleaved caspase 3, cleaved caspase 9, cyclooxygenase 2 (COX2), focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), phospho-Akt, nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, phospho-JNK, and phospho-ERK and decreased (P < 0.05) muscle procaspase 3, procaspase 9, and NF-κB inhibitor α. In conclusion, the downregulation of SelP-L, GPx1, GPx4, Sep15, SelW, and SelN by dietary Se deficiency might account for induced oxidative stress and the subsequent peroxidative damage of chick muscle cells via the activation of the p53/caspase 9/caspase 3, COX2/FAK/PI3K/Akt/NF-κB, and p38 MAPK/JNK/ERK signaling pathways. Metabolism of peroxides and redox regulation are likely to be the mechanisms whereby these selenoproteins prevented the onset of NMD in chicks.     

Selenium Deficiency Influences Nitric Oxide and Selenoproteins in Pancreas of Chickens

Selenium (Se) deficiency induces pancreatic atrophy in chickens, but the molecular mechanism remains unclear. In this study, we investigated the effect of dietary Se deficiency on the expressions of 25 selenoproteins and the content of nitric oxide (NO) and examined the relationship between selenoproteins and NO. Chickens (180; 1 day old) were randomly divided into two groups, low (L) group (fed with Se deficient (Se 0.033 mg/kg) diet) and control (C) group (fed with normal (Se 0.2 mg/kg) diet). Then, pancreas was collected at 15, 25, 35, 45, and 55 days, and the content of NO, the activity of inducible NO synthase (iNOS), and the messenger RNA (mRNA) levels of 25 selenoproteins and iNOS were measured. The results showed that 25 selenoproteins were decreased (P?P?Thioredoxin reductase 2 (TXNRD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3), selenoprotein I (SELI), iodothyronine deiodinase 1 (DIO1), selenoprotein P1 (SEPP1), selenoprotein W1 (SEPW1), selenoprotein O (SELO), selenoprotein T (SELT), selenoprotein M (SELM), selenoprotein X1 (SEPX1), and SPS2 were excessively decreased (P?iNOS activity, and mRNA level were increased strikingly compared with C group (P?相似文献   

Selenium nanoparticles are required for the optimum growth behavior,antioxidative capacity,and liver wellbeing of Striped catfish (Pangasianodon hypophthalmus)

Selenium (Se) is a multifunctional trace element required in specific amounts for the optimal growth of aquatic finfish species. For this reason, this study investigated the effect of Se nanoparticles on the growth behavior, antioxidative capacity, and liver wellbeing of Striped catfish (Pangasianodon hypophthalmus). Striped catfish fed varying Se nanoparticles levels (0. 0.5, 1, and 2 mg/kg) in triplicate units and kept for 60 days. Striped catfish delivered dietary Se nanoparticles had markedly increased growth performance, specific growth rate (SGR), consumed feed, and protein efficiency ratio but reduced feed conversion ratio (FCR). The whole body, liver, muscle, and gills have higher Se accumulation levels in fish that received Se nanoparticles than the control with the highest level in fish fed 2 mg/kg. The carcass composition showed higher protein content in fish fed 1 and 2 mg/kg (p = 0.001 and 0.001) and higher ash content (p = 0.001 and 0.002) in fish fed 2 mg/kg than the remaining groups. Superoxide dismutase was meaningfully activated in Striped catfish delivered 1 and 2 mg Se nanoparticles/kg compared with the control (p < 0.05). Also, catalase and glutathione peroxidase activities were higher, and malondialdehyde level was lower in Striped catfish fed Se nanoparticles at 0.5, 1, and 2 mg/kg than the control (p < 0.05). The villi exhibited a visible increase in both height and branching with an increased level of Se nanoparticles in addition to the increased number of goblet cells. The Se nanoparticles-treated fish revealed dose-dependent modifications fluctuated from diffuse fatty vacuolization in hepatocytes with eccentric pyknotic hepatocytes nuclei. In conclusion, Se nanoparticles are required for the optimum growth behavior, antioxidative capacity, and liver wellbeing of Striped catfish. Based on SGR and FCR data's regression analysis, Se nanoparticles are recommended at 1.02–1.11 mg/kg diet.     

氧化油脂对斑点叉尾鮰生长、体色和抗氧化能力的影响

为考察正常及氧化鱼油、豆油、混合油脂(鱼油﹕豆油=1﹕1)对斑点叉尾鮰(Ictalurus punctatus)生长性能、体色和肝脏抗氧化能力的影响, 设计6组等氮等脂饲料, 分别添加6%鱼油、6%豆油、3%鱼油+3%豆油、6%氧化鱼油、6%氧化豆油、3%氧化鱼油+3%氧化豆油, 饲喂6组初始体重(150.5±4.2 g)的斑点叉尾鮰8周, 每组3个重复, 每个重复14尾鱼。结果表明, 摄食6%鱼油、6%豆油、3%鱼油+3%豆油饲料的斑点叉尾鮰在增重率、饲料系数、肌肉组成、体色和肝脏抗氧化指标上均无显著差异(P>0.05); 摄食3组氧化油脂饲料后, 鱼体增重率和肌肉粗脂肪含量降低(P<0.05), 饲料系数和背部、尾部皮肤b*(黄度值)增加(P<0.05), 肝脏丙二醛(MDA)和血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)和直接胆红素升高(DBIL)(P<0.05), 肝脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原型谷胱甘肽降低(GSH)(P<0.05), 而肌肉色度值(L*、a* 、b*)和肌肉水分、粗蛋白质、灰分含量无显著差异(P>0.05)。以上结果表明, 6%氧化油脂(鱼油、豆油或混合油脂)导致斑点叉尾鮰生长性能下降、皮肤黄度增加、肝脏抗氧化能力受损; 豆油可替代斑点叉尾鮰饲料中鱼油的使用, 而不会对生长产生负面影响。     

The Effects of Supplementary Cr3 (Chromium(III) Propionate Complex) on the Mineral Status in Healthy Female Rats

Circulating concentration of the essential trace element selenium (Se) was significantly lower in inflammatory disorders. Although Se plays physiological roles mainly through the function of 25 selenoproteins, the response of the selenogenome in immune tissues during inflammatory reactions remains unclear. The objective of this study was to determine the Se retention and selenogenome expression in immune tissues during the lipopolysaccharide (LPS)-induced inflammatory response in porcine. A total of 12 male pigs were randomly divided into two groups and injected with LPS or saline. After 4 h postinjection, blood samples were collected and pigs were euthanized. Pigs challenged with LPS had 36.8 and 16.6 % lower (P < 0.05) Se concentrations in the serum and spleen, respectively, than those injected with saline. Moreover, the activities of GPX decreased (P < 0.05) by 23.4, 26.6, and 30.4 % in the serum, thymus, and lymph node, respectively, in the pigs injected with LPS. Furthermore, the LPS challenge altered (P < 0.05) the mRNA expression of 14, 16, 10, and 6 selenoprotein genes in the liver, spleen, thymus, and lymph node, respectively. Along with 10 previously reported selenoprotein genes, the response of Txnrd2, Txnrd3, Sep15, Selh, Seli, Seln, Selo, Selt, Selx, and Sephs2 to inflammatory reaction in immune tissues were newly illustrated in this study. In conclusion, the LPS-induced inflammatory response impaired Se metabolism and was associated with dysregulation of the selenogenome expression in immune tissues.     

Dietary selenium levels modulates antioxidant,cytokine and immune response and selenoproteins mRNA expression in rats under heat stress condition

BackgroundHigher environmental temperature is a major abiotic stress factor for animals and human beings. The selenium (Se) is an important trace mineral having diverse health promoting effects under stress conditions. However, studies on dietary requirement of selenium under prolonged heat stress condition are lacking. Present study discern the effect of higher dietary Se levels on antioxidant, cytokine, haemato-biochemical profile, and immune response, and the selenoproteins mRNA expression in rats under prolonged heat stress (HS) condition.MethodsWeaned Wistar rats (4 wk age; 67.6 ± 1.53 g BW; n = 72) housed under thermoneutral (TN) or HS conditions and fed with purified diets containing three graded Se levels were divided in six experimental groups. The groups were 1) TN control with 138 ppb Se (TN_CON), 2) HS control with 138 ppb Se (HS_CON), 3) TN with higher Se @ 291 ppb (TN_Se1), 4) HS with higher Se @ 291 ppb (HS_Se1) 5) TN with higher Se @ 460 ppb (TN_Se2), 6) HS with higher Se @ 460 ppb (HS_Se2). Rats in all the six groups were maintained in TN environmental conditions (57.3 ± 0.22 temperature humidity index; THI) for initial 28 days period. Subsequently, rats of HS groups were exposed to 77.0 ± 0.11 THI for 6 h/d in a psychrometric chamber for last fourteen days.ResultsHigher dietary Se (291 and 460 ppb) significantly improved the blood hemoglobin concentration and reduced serum alanine aminotransferase activity of rats under HS conditions. The serum triiodothyronine and insulin levels were significantly higher in high dietary Se groups irrespective of the environmental conditions. Similarly, the serum reduced glutathione levels, and catalase and superoxide dismutase enzyme activity were increased and malondialdehyde levels were reduced in high dietary Se groups irrespective of stress conditions. The glutathione peroxidase (GPx) activity was significantly higher in 460 ppb dietary Se groups as compared to other groups. The serum pro-inflammatory cytokine interleukin (IL)− 1 was declined, whereas the anti-inflammatory cytokine IL-10 level was increased in high dietary Se fed rats under both HS and TN conditions with 460 ppb dietary Se groups showing pronounced effects. Further, there was heat stress- and dietary Se level dependent- up regulation in hepatic GPx and iodothyronine deiodinase-II mRNA expression and similar pattern was noticed in hepatic thioredoxin reductase mRNA expression. The selenoprotein-P mRNA expression was up regulated in 460 ppb Se fed HS group as compared to CON and Se1_C groups. High dietary Se improved the humoral immune response 7d after antigen inoculation under HS conditions whereas cell-mediated immune response was augmented in rats fed higher Se under TN condition.ConclusionIt is concluded that under prolonged heat stress conditions the dietary requirement of Se may be increased to 460 ppb for improving the antioxidant status and humoral immune response, cytokine levels, modulating the thyroid and insulin hormone, and the selenoproteins mRNA expression of rats.     

Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer

Selenium (Se), a dietary trace metal essential for human health, is incorporated into ~25 selenoproteins including selenoprotein S (SelS) and the 15-kDa selenoprotein (Sep15) both of which have functions in the endoplasmic reticulum protein unfolding response. The aim of this study was to investigate whether genetic variants in such selenoprotein genes are associated with altered risk of colorectal cancer (CRC). A Korean population of 827 patients with CRC and 733 healthy controls was genotyped for 7 SNPs in selenoprotein genes and one SNP in the gene encoding manganese superoxide dismutase using Sequenom technology. Multivariate logistic regression analysis showed that after adjustment for lifestyle factors three SNP variants were associated with altered disease risk. There was a mean odds ratio of 2.25 [95% CI 1.13,4.48] in females homozygous TT for rs34713741 in SELS with the T variant being associated with higher risk of rectal cancer, and odds ratios of 2.47 and 2.51, respectively, for rs5845 and rs5859 in SEP15 with the minor A and T alleles being associated with increased risk of male rectal cancer. The data indicate that the minor alleles for rs5845, rs5859 and rs34713741 are associated with increased rectal cancer risk and that the effects of the three SNPs are dependent on gender. The results highlight potential links between Se, the function of two selenoproteins involved in the protein unfolding response and CRC risk. Further studies are required to investigate whether the effects of the variants on CRC risk are also modulated by dietary Se intake.     

Reduced macrophage selenoprotein expression alters oxidized lipid metabolite biosynthesis from arachidonic and linoleic acid

Uncontrolled inflammation is an underlying etiology for multiple diseases and macrophages orchestrate inflammation largely through the production of oxidized fatty acids known as oxylipids. Previous studies showed that selenium (Se) status altered the expression of oxylipids and magnitude of inflammatory responses. Although selenoproteins are thought to mediate many of the biological effects of Se, the direct effect of selenoproteins on the production of oxylipids is unknown. Therefore, the role of decreased selenoprotein activity in modulating the production of biologically active oxylipids from macrophages was investigated. Thioglycollate-elicited peritoneal macrophages were collected from wild-type and myeloid-cell-specific selenoprotein knockout mice to analyze oxylipid production by liquid chromatography/mass spectrometry as well as oxylipid biosynthetic enzyme and inflammatory marker gene expression by quantitative real-time polymerase chain reaction. Decreased selenoprotein activity resulted in the accumulation of reactive oxygen species, enhanced cyclooxygenase and lipoxygenase expression and decreased oxylipids with known anti-inflammatory properties such as arachidonic acid-derived lipoxin A₄ (LXA₄) and linoleic acid-derived 9-​oxo-octadecadienoic acid (9-oxoODE). Treating RAW 264.7 macrophages with LXA₄ or 9-oxoODE diminished oxidant-induced macrophage inflammatory response as indicated by decreased production of TNFα. The results show for the first time that selenoproteins are important for the balanced biosynthesis of pro- and anti-inflammatory oxylipids during inflammation. A better understanding of the Se-dependent control mechanisms governing oxylipid biosynthesis may uncover nutritional intervention strategies to counteract the harmful effects of uncontrolled inflammation due to oxylipids.     

In silico identification of novel selenoproteins in the Drosophila melanogaster genome

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3′-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.     

Selenoproteins and heat shock proteins play important roles in immunosuppression in the bursa of Fabricius of chickens with selenium deficiency

Selenium (Se) is necessary for the immune system in chicken and mediates its physiological functions through selenoproteins. Heat shock proteins (Hsps) are indispensable for maintaining normal cell function and for directing the immune response. The aim of the present study was to investigate the effects of Se deficiency on the messenger ribonucleic acid (mRNA) expression levels of selenoproteins and Hsps as well as immune functions in the chicken bursa of Fabricius. Two groups of chickens, namely the control and Se-deficient (L group) groups, were reared for 55 days. The chickens were offered a basal diet, which contained 0.15 mg Se/kg in the diet fed to the control group and 0.033 mg Se/kg in the diet fed to the L group. We performed real-time quantitative polymerase chain reactionto detect the mRNA expression levels of selenoproteins and Hsps on days 15, 25, 35, 45 and 55. Western blotting was used to determine the protein expression levels of Hsps on days 35, 45 and 55, and immune functions were assessed through an enzyme-linked immunosorbent assay on days 15, 35, and 55. The data showed that the mRNA expression levels of selenoproteins, such as Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, GPx1, GPx2, GPx3 GPx4, Sepp1, Selo, Sel-15, Sepx1, Sels, Seli, Selu, Selh, and SPS2, were significantly lower (P < 0.05) in the L group compared with the control group. Additionally, the mRNA and protein expression levels of Hsps (Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90) were also significantly higher (P < 0.05) in the L group. The expression levels of IL-2, IL-6, IL-8, IL-10, IL-17, IL-1β, IFN-α, IFN-β, and IFN-γ were significantly lower (P < 0.05) and TNF-α was significantly higher (P < 0.05) in the L group compared with the control group. Our results show that immunosuppression was accompanied by a downregulation of mRNA expression levels of selenoproteins and an upregulation of the Hsp mRNA expression levels. Thus, Se deficiency causes defects in the chicken bursa of Fabricius, and selenoproteins and Hsps play important roles in immunosuppression in the bursa of Fabricius of chickens with Se deficiency.     

Selenium homeostasis in human brain cells: Effects of copper (II) and Se species

BackgroundBoth essential trace elements selenium (Se) and copper (Cu) play an important role in maintaining brain function. Homeostasis of Cu, which is tightly regulated under physiological conditions, seems to be disturbed in Alzheimer´s (AD) and Parkinson´s disease (PD) patients. Excess Cu promotes the formation of oxidative stress, which is thought to be a major cause for development and progression of neurological diseases (NDs). Most selenoproteins exhibit antioxidative properties and may counteract oxidative stress. However, expression of selenoproteins is altered under conditions of Se deficiency. Serum Se levels are decreased in AD and PD patients suggesting Se as an important factor in the development and progression of NDs. The aim of this study was to elucidate the interactions between Cu and Se in human brain cells particularly with respect to Se homeostasis.MethodsFirstly, modulation of Se status by selenite or SeMet were assessed in human astrocytes and human differentiated neurons. Therefore, cellular total Se content, intra- and extracellular selenoprotein P (SELENOP) content, and glutathione peroxidase (GPX) activity were quantified. Secondly, to investigate the impact of Cu on these markers, cells were exposed to copper(II)sulphate (CuSO₄) for 48 h. In addition, putative protective effects of Se on Cu-induced toxicity, as measured by cell viability, DNA damage, and neurodegeneration were investigated.ResultsModulation of cellular Se status was strongly dependent on Se species. In detail, SeMet increased total cellular Se and SELENOP content, whereas selenite led to increased GPX activity and SELENOP excretion. Cu treatment resulted in 133-fold higher cellular Cu concentration with a concomitant decrease in Se content. Additionally, SELENOP excretion was suppressed in both cell lines, while GPX activity was diminished only in astrocytes. These effects of Cu could be partially prevented by the addition of Se depending on the cell line and Se species used. While Cu-induced oxidative DNA damage could not be prevented by addition of Se regardless of chemical species, SeMet protected against neurite network degeneration triggered by Cu.ConclusionCu appears to negatively affect Se status in astrocytes and neurons. Especially with regard to an altered homeostasis of those trace elements during aging, this interaction is of high physiological relevance. Increasing Cu concentrations associated with decreased selenoprotein expression or functionality might be a promoting factor for the development of NDs.     

Effects of acclimation salinity on the expression of selenoproteins in the tilapia,Oreochromis mossambicus

Selenoproteins are ubiquitously expressed, act on a variety of physiological redox-related processes, and are mostly regulated by selenium levels in animals. To date, the expression of most selenoproteins has not been verified in euryhaline fish models. The Mozambique tilapia, Oreochromis mossambicus, a euryhaline cichlid fish, has a high tolerance for changes in salinity and survives in fresh water (FW) and seawater (SW) environments which differ greatly in selenium availability. In the present study, we searched EST databases for cichlid selenoprotein mRNAs and screened for their differential expression in FW and SW-acclimated tilapia. The expression of mRNAs encoding iodothyronine deiodinases 1, 2 and 3 (Dio1, Dio2, Dio3), Fep15, glutathione peroxidase 2, selenoproteins J, K, L, M, P, S, and W, was measured in the brain, eye, gill, kidney, liver, pituitary, muscle, and intraperitoneal white adipose tissue. Gene expression of selenophosphate synthetase 1, Secp43, and selenocysteine lyase, factors involved in selenoprotein synthesis or in selenium metabolism, were also measured. The highest variation in selenoprotein and synthesis factor mRNA expression between FW- and SW-acclimated fish was found in gill and kidney. While the branchial expression of Dio3 was increased upon transferring tilapia from SW to FW, the inverse effect was observed when fish were transferred from FW to SW. Protein content of Dio3 was higher in fish acclimated to FW than in those acclimated to SW. Together, these results outline tissue distribution of selenoproteins in FW and SW-acclimated tilapia, and indicate that at least Dio3 expression is regulated by environmental salinity.     

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein

Proteins containing the 21st amino acid selenocysteine (Sec) are present in the three domains of life. However, within lower eukaryotes, particularly parasitic protists, the dependence on the trace element selenium is variable as many organisms lost the ability to utilize Sec. Herein, we analyzed the genomes of Trypanosoma and Leishmania for the presence of genes coding for Sec-containing proteins. The selenoproteomes of these flagellated protozoa have three selenoproteins, including distant homologs of mammalian SelK and SelT, and a novel multidomain selenoprotein designated SelTryp. In SelK and SelTryp, Sec is near the C-terminus, and in all three selenoproteins, it is within predicted redox motifs. SelTryp has neither Sec- nor cysteine-containing homologs in the human host and appears to be a Kinetoplastida-specific protein. The use of selenium for protein synthesis was verified by metabolically labeling Trypanosoma cells with ⁷⁵Se. In addition, genes coding for components of the Sec insertion machinery were identified in the Kinetoplastida genomes. Finally, we found that Trypanosoma brucei brucei cells were highly sensitive to auranofin, a compound that specifically targets selenoproteins. Overall, these data establish that Trypanosoma, Leishmania and likely other Kinetoplastida utilize and depend on the trace element selenium, and this dependence is due to occurrence of selenium in at least three selenoproteins.