This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obe...This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.展开更多
Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting...Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting against damage induced by oxidative stress.This study aimed to investigate the effects and possible mechanism of selenium on selenoproteins expression in EA.hy926 cells induced by oxidized low density lipoprotein(oxLDL).The impact of selenium on the viability of EA.hy926 cells was detected by the methylthiazolyldiphenyltetrazolium bromide(MTT)method,and intracellular reactive oxygen species(ROS)level and mitochondrial membrane potential were assessed by fluorescent probe DCFH-DA and JC-1,respectively.RNA-seq,quantitative real-time polymerase chain reaction(qPCR),and Western blot were used to investigate the selenoprotein expression.Selenoprotein mRNA translation efficiency was analyzed by ribosome profiling(Ribo-Seq)coupled with transcriptomics.Our data showed that selenium supplementation(0.5μmol/L)significantly decreased ROS production,increased mitochondrial inner membrane potential and increased the proliferative activity of EA.hy926 cells induced by oxLDL.Moreover,The protective effects of selenium against oxLDL-induced EA.hy926 cell injury were associated with the upregulation of the expressions of selenoproteins glutathione peroxidase 1(GPX1),glutathione peroxidase 4(GPX4),and thioredoxin reductase 1(TXNRD1).Furthermore,the expressions of selenoproteins GPX1 and GPX4 were hierarchically controlled,but the expressions of selenoproteins TXNRD1 were mainly regulated by oxLDL.Finally,Ribo-Seq coupled with transcriptomics results demonstrated that the expressions of selenoproteins GPX1,GPX4,and TXNRD1 were regulated at the translation process level.These findings suggested that selenium could have preventive effects in oxLDL induced EA.hy926 cell injury by regulating the selenoprotein expression,and the selenoproteins expressions at the translation level in vascular endothelial cells need further study.展开更多
Selenium（Se） is an essential trace element in many organisms, its biological function is mainly in the form of selenoproteins, and plant selenoproteins have antioxidant, anti-cancer, and immunity enhancing effects. ...Selenium（Se） is an essential trace element in many organisms, its biological function is mainly in the form of selenoproteins, and plant selenoproteins have antioxidant, anti-cancer, and immunity enhancing effects. This study reviewed the existing forms of selenium in plants, selenoproteins classification and selenoproteins extraction methods and proposed future research directions.展开更多
Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by diet...Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by dietary selenium(Se)level.Here,we developed the dietary oxidative stress(DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation,which is accompanied by mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and protein and lipid metabolism disorders.Supplementation with Se(0.3,0.6 or 0.9 mg Se/kg)in form of hydroxy selenomethionine(OH-SeMet)linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins,which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle,and the mitigation of mitochondrial dysfunction and ER stress.What’s more,selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle.However,several parameters such as the activity of GSH-Px and T-SOD,the protein abundance of JNK2,CLPP,SELENOS and SELENOF did not show dose-dependent changes.Notably,several key selenoproteins such as MSRB1,SELENOW,SELENOM,SELENON and SELENOS play the unique roles during this protection.Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress,recover protein and lipid biosynthesis,thus alleviate skeletal muscle growth retardation.Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.展开更多
Objective Iodothyronine deiodinases(DIOs)are important selenoproteins that play a key role in the bone and joint diseases.Osteoarthritis(OA)is the most prevalent joint disease especially in elders.This bioinformatic a...Objective Iodothyronine deiodinases(DIOs)are important selenoproteins that play a key role in the bone and joint diseases.Osteoarthritis(OA)is the most prevalent joint disease especially in elders.This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis.Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques,mcluding GenCLip 3.0,Database for Annotation,Visualization and Integrated Discovery(DAVID),STRING,Cytoscape,and Network Analyst.The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus(GEO)database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3.Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine;GO analysis showed that DIOs were mainly involved in biological processes,such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling;SULT1A1 was the core node of the PPI network;miRNAs and thyroid hormones had some iterations with DIO1 and DI02;Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients(SMD=0.31,95%CI:0.03,0.59,P=0.03).Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone.And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.展开更多
AIM: To investigate the expression of selenoprotein P mRNA (SePmRNA) in tissues of normal liver, liver cirrhosis and hepatocellular carcinoma (HCC), and its relationship with HCC occurrence and development. METHODS: T...AIM: To investigate the expression of selenoprotein P mRNA (SePmRNA) in tissues of normal liver, liver cirrhosis and hepatocellular carcinoma (HCC), and its relationship with HCC occurrence and development. METHODS: The expression of SePmRNA in tissues of normal liver, liver cirrhosis and HCC were detected by in situ hybridization using a cDNA probe. RESULTS: The enzyme digesting products of PBluescript-H uman Selenoprotein P were evaluated by electrophoresis. The positive expression of SePmRNA was found in the tissues of normal liver, liver cirrhosis and HCC. The expression of SeP mRNA was found in hepatic interstitial substance, especially in endothelial cells and lymphocytes of vasculature. The positive rate of SePmRNA in normal liver tissue was 84.6% (11/13) and the positive signals appeared in the nucleus and cytoplasm, mostly in the nucleolus, and the staining granules were larger in the nucleolus and around the nucleus. The positive rate of SePmRNA in liver cirrhosis tissue was 45.0% (9/20) and the positive signals were mainly in the nucleolus and cytoplasm, being less around the nucleus and inner nucleus than that in normal liver tissue. The positive rate of SePmRNA in HCC tissue was 30.0% (9/30) and the positive signals were in the cytoplasm, but less in the nucleus. CONCLUSION: SePmRNA expression in the tissues of normal liver and HCC is significantly different (84.6% vs 30.0%, P = 0.003), suggesting that SeP might play a role in the occurrence and development of HCC.展开更多
The nucleotide sequences of the open reading frames of cDNAs for selenoprotein W from skeletal muscle of rat, mouse, sheep, rhesus monkey and human are reported. Theoretical translation of the coding sequences indicat...The nucleotide sequences of the open reading frames of cDNAs for selenoprotein W from skeletal muscle of rat, mouse, sheep, rhesus monkey and human are reported. Theoretical translation of the coding sequences indicated highly similar proteins of 88 (mouse and rat) or 87 (human, monkey and sheep) amino acids. In 73 of 88 positions the specified amino acids are identical for all five proteins. TGA encoding selenocysteine is the 13th codon of all the cDNAs. The rnouse, rat and sheep open reading frames terminate with TGA but the human and rhesus monkey coding regions terminate with TAA. The encoded amino acid sequences are identical for the rat and mouse proteins, and for the human and monkey proteins. The similarity of the cDNAs continues in the 3' noncoding regions through the putative selenocysteine insertion sequence (SEClS) elements which are required for correct interpretation of the selenocysteine codon. The region between the SECIS elements and the polyadenylation signals showed much lower similarity. The cloned rat gene for selenoprotein W is 5000 bases long,with the 663 bases of the cDNA in six exons. The transcription start site was identified by nuclease protection assay to be 16 bases upstream of the longest cDNA clone. A canonical TATA box occurs 150 bases upstream, but the assay did not indicate the presence of longer mRNAs展开更多
Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs...Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs in higher animals and further we exarnine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); (iii) the effect of selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis of the modified bases on Sec tRNA in Xenopus oocytes展开更多
Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that...Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect, although low molecular weight seleno-compounds have also been posited to selectively induce apoptosis in transformed cells. To address the effects of selenium supplementation on selenoprotein expression in prostate cells, we have undertaken an analysis of antioxidant selenoprotein expression as well as selenium toxicity in non-tumorigenic prostate epithelial cells （RWPE- 1 ） and prostate cancer cells （LNCaP and PC-3）. Our results show that two of the glutathione peroxidase family members （GPX1 and GPX4） are highly induced by supplemental selenium in prostate cancer cells but only slightly induced in RWPE-1 cells. In addition, GPX 1 levels are dramatically lower in PC-3 cells as compared to RWPE- 1 or LNCaP cells. GPX2 protein and mRNA, however, are only detectable in RWPE-1 cells. Of the three selenium compounds tested （sodium selenite, sodium selenate and selenomethionine）, only sodium selenite shows toxicity in a physiological range of selenium concentrations. Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells.展开更多
This paper reviews some recent findings on the interactions between selenium deficiency and iodine deficency. Both micronutrients can control the levels of selenoprotein mRNAs, particularly in the thyroid and brain. W...This paper reviews some recent findings on the interactions between selenium deficiency and iodine deficency. Both micronutrients can control the levels of selenoprotein mRNAs, particularly in the thyroid and brain. When selenium and iodine supplies are limiting the compensatory mechanisms work to minimise adverse effects on thyroid hormone metabolsm and thus neurological developtnent. The mechanisms for regulation of selenoproteins in selenium and iodine deficiency are however very tissue-specific. For example, unlike the brain and thyroid,brown adipose tissue is unable to retain selenoproteins in selenium and iodine deficiency and is therefore at greater risk from injurious effects of the deficiencies.展开更多
Selenium has been recognized as an essential nutrient in animals since the 1950s. Demonstration of the role of dietary selenium in protection from oxidative stress foIlowed in the early 1970s, and was largely attribut...Selenium has been recognized as an essential nutrient in animals since the 1950s. Demonstration of the role of dietary selenium in protection from oxidative stress foIlowed in the early 1970s, and was largely attributed to its presence as an integral part of cellular glutathione peroxidase. However, the functions of this enzyme did not explain many of the other effects of selenium deficiency. The identification of other mammalian selenoproteins during the last few years has provided new insights into the functions of this trace nutrient. The discovery that type 1 deiodinase (D1) is a selenoenzyme, in addition to unveiling an essential role for selenium in thyroid hormone action, has had more far-reaching implications. Studies of this protein opened the door for investigation of the requirements for eukaryotic selenoprotein synthesis,and the features that distinguish this pathway from the corresponding prokaryotic pathway.Selenium is present in a number of prokaryotic and eukaryotic proteins in the form of the unusual amino acid, selenocysteine. Incorporation of selenocysteine into these proteins requires a novel translation step in which UGA specifies selenocysteine insertion. Since UGA codons are typically recognized as translation stop signals, an intriguing question is raised: How does a cell recognize and distinguish a UGA selenocysteine codon from a UGA stop codon? In this review, we will focus on what is known about selenocysteine incorporation in eukaryotes, briefly summarizing initial studies and discussing a few recent advances in our understanding of this unique 'recoding' process展开更多
After labeling of rats in vivo with 75Se and protein separation by sodium dodecyl sulfatepolyacrylamide gel electrophoresis more than 25 Se-containing bands could be distinguished.Of those proteins which were detected...After labeling of rats in vivo with 75Se and protein separation by sodium dodecyl sulfatepolyacrylamide gel electrophoresis more than 25 Se-containing bands could be distinguished.Of those proteins which were detected only in certain compartments and might therefore have tissue-specific functions, two were chosen for detailed investigation.A 15 kDa-protein was found in the prostatic epithelium where it accounted for about two thirds of the protein-bound 75Se. It was mainly present in the cytosol but was not released into the prostatic secretion. After gel chromatography it was found in the fraction which contained proteins with molecular masses of about 300 kDa. Using two-dimensional electrophoresis a plvalue of about 4. 5 was determined.In the testis a specific Se-containing 34 kDa-protein was observed which appeared after the onset of puberty. It was localized in the spermatid nuclei where it contained about 80% of the Se tracer present and was found to be bound to the DNA. After extraction it partly disintegrated into a 20 kDa-protein.Both compounds contain Se in the form of selenocysteine. The fact that their formation had priority over that of glutathione peroxidase during insufficient Se intake is an indication of their biological significance. Special interest in the prostatic epithelial selenoprotein derives from a possible inverse relationship between the Se status and the incidence of prostate cancer observed in epidemiological studies, whereas with the 34 kDa-selenoprotein its appearance during the condensation phase of the spermatid nuclei might suggest its participation in some processes of sperm maturation展开更多
Ebola virus infection is the present public health problem.The trend of worldwide epidemic becomes the serious consideration for this infection.The Ebola virus infection has main clinical manifestation as acute febril...Ebola virus infection is the present public health problem.The trend of worldwide epidemic becomes the serious consideration for this infection.The Ebola virus infection has main clinical manifestation as acute febrile illness with hemorrhagic episode.The problem of hemostatic disturbance can be seen.Focusing on the palhophysiology.selenium plays an important role in the blood clotting regulation.The study on the selenoprotein of the Ebola virus can be useful for further understanding on the pathology of the infection.Here,the authors use metallomics analysis for assessment of Ebola virus genome.According to this study,the selenoprotein portion within Ebola virus genome can be detected at position 1046-1115.展开更多
Objective:To investigate if the protective effect ofα-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHG...Objective:To investigate if the protective effect ofα-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHGPx;GPx4) and selenoprotein P (SelPP) that have roles against oxidative stress.Methods:Forty female mice were randomly assigned into natural control (CON), positive control (ETOH), low-, medium-, and high-α-tocopherol-supplemented-ethanol groups (LTOC, MTOC, HTOC, respectively). CON received drinking water without ethanol while ETOH, LTOC, MTOC and HTOC groups received 20% ethanol in drinking water. The supplemented groups were given respective dosages ofα-tocopherol, 0.410, 0.819, and 1.640 mg/g body weight, at day 14 before mating onwards to the day 9 of gestation. At 10.5 ED of gestation (1100 h), the pregnant females were sacrificed by cervical dislocation and the embryos were harvested. Total RNA were extracted, cDNA synthesis and qRT- PCR analyses were carried out.Results: The level of expression of PHGPx in the positive control was significantly lower than that of the natural control. Among the threeα-tocopherol-supplemented groups, only the medium dose- group was significantly higher than the positive control. The level of expression of SelPP in the positive control was significantly lower than those of the natural control, the low- and medium- dose -tocopherol supplemented groups. In the high dose-α-tocopherol supplemented group, the level of expression was not significantly different from the positive control but significantly lower than the natural control.Conclusions: The activity of the selenoproteins PHGPx and SelPP are involved in the internetwork of antioxidative enzymes with vitamin E when given up to a medium dose only and is one of the possible pathways of shielding embryonic development against the impact of ethanol on brain morphogenesis. This study strengthens the impact of dietaryα-tocopherol and Selenium supplement during the critical period of pregnancy.展开更多
The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after ...The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.展开更多
Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to stau...Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to staurosporine(STS)and hyperthermia.Methods A stable SELENOM-knockdown(SELENOM-KD)cell line was created.We measured reactive oxygen species(ROS),mitochondrial membrane potential(ΔΨm),cell death,and apoptotic gene expression.Results SELENOM-KD increased basal ROS levels and induced mitochondrial dysfunction.It sensitized cells to STS-induced apoptosis,enhancing the upregulation of pro-apoptotic genes.Conversely,under hyperthermia(42°C),SELENOM-KD cells exhibited significant thermoresistance,with 52%survival vs.99%death in controls,associated with suppressed pro-apoptotic signaling.Conclusions SELENOM is a critical redox and mitochondrial regulator in GBM.Its loss produces a context-dependent effect on cell fate:sensitizing to chemical apoptosis while conferring resistance to hyperthermia.SELENOM expression is a promising predictive biomarker for stratifying GBM patients for hyperthermia-based therapies.展开更多
The computer program RNA Draw was used to identify the secondary structures in the 3’untranslated regions (3’UTRs) of the mRNAs from 46 eukaryotic seleno-proteins among 7 species. The program found one or two possib...The computer program RNA Draw was used to identify the secondary structures in the 3’untranslated regions (3’UTRs) of the mRNAs from 46 eukaryotic seleno-proteins among 7 species. The program found one or two possible SECIS elements in these selenoproteins. The SECIS element consists of a stem-loop or hairpin structure with three conserved sequences of AUGA-(A)AA-GA. SECIS element was not found by the RNA Draw program in randomly selected non-selenoproteins. The results showed that SECIS element is the unique character of the genes ofeukaryotic selenoproteins. Thus it is possible to use RNA Draw to search the SECIS elements in gene bank for potential new selenoproteins.展开更多
文摘This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.
基金supported by grants from the National Natural Science Foundation of China(NSFC,81960588)the Ningxia Natural Science Foundation(2020AAC03146)support from the Ningxia Medical University。
文摘Selenium is a crucial trace element that contributes to physiological processes in the body as selenoproteins.Selenoproteins serve as an integral role in the body in controlling the redox state of cells and protecting against damage induced by oxidative stress.This study aimed to investigate the effects and possible mechanism of selenium on selenoproteins expression in EA.hy926 cells induced by oxidized low density lipoprotein(oxLDL).The impact of selenium on the viability of EA.hy926 cells was detected by the methylthiazolyldiphenyltetrazolium bromide(MTT)method,and intracellular reactive oxygen species(ROS)level and mitochondrial membrane potential were assessed by fluorescent probe DCFH-DA and JC-1,respectively.RNA-seq,quantitative real-time polymerase chain reaction(qPCR),and Western blot were used to investigate the selenoprotein expression.Selenoprotein mRNA translation efficiency was analyzed by ribosome profiling(Ribo-Seq)coupled with transcriptomics.Our data showed that selenium supplementation(0.5μmol/L)significantly decreased ROS production,increased mitochondrial inner membrane potential and increased the proliferative activity of EA.hy926 cells induced by oxLDL.Moreover,The protective effects of selenium against oxLDL-induced EA.hy926 cell injury were associated with the upregulation of the expressions of selenoproteins glutathione peroxidase 1(GPX1),glutathione peroxidase 4(GPX4),and thioredoxin reductase 1(TXNRD1).Furthermore,the expressions of selenoproteins GPX1 and GPX4 were hierarchically controlled,but the expressions of selenoproteins TXNRD1 were mainly regulated by oxLDL.Finally,Ribo-Seq coupled with transcriptomics results demonstrated that the expressions of selenoproteins GPX1,GPX4,and TXNRD1 were regulated at the translation process level.These findings suggested that selenium could have preventive effects in oxLDL induced EA.hy926 cell injury by regulating the selenoprotein expression,and the selenoproteins expressions at the translation level in vascular endothelial cells need further study.
基金Supported by Guangxi Scientific Research and Technological Development Program(GKH 15104001-22)Guangxi Natural Science Foundation(2014GXNSFBA118139)+2 种基金Special Fund for Basal Scientific Research of Guangxi Academy of Agricultural Sciences(GN 2014YD13)Nanning Scientific Research and Technological Development Program(20152054-13)Scientific Research and Technological Development Program of Xixiangtang District of Nanning City(2015312)~~
文摘Selenium（Se） is an essential trace element in many organisms, its biological function is mainly in the form of selenoproteins, and plant selenoproteins have antioxidant, anti-cancer, and immunity enhancing effects. This study reviewed the existing forms of selenium in plants, selenoproteins classification and selenoproteins extraction methods and proposed future research directions.
基金supported by the National Natural Science Foundation of China(No.31772643 and 31272468)the Special Research Funding for Discipline Construction in Sichuan Agricultural University(No.03570126)Adisseo France(18SES533).
文摘Background The skeletal muscle of pigs is vulnerable to oxidative damage,resulting in growth retardation.Selenoproteins are important components of antioxidant systems for animals,which are generally regulated by dietary selenium(Se)level.Here,we developed the dietary oxidative stress(DOS)-inducing pig model to investigate the protective effects of selenoproteins on DOS-induced skeletal muscle growth retardation.Results Dietary oxidative stress caused porcine skeletal muscle oxidative damage and growth retardation,which is accompanied by mitochondrial dysfunction,endoplasmic reticulum(ER)stress,and protein and lipid metabolism disorders.Supplementation with Se(0.3,0.6 or 0.9 mg Se/kg)in form of hydroxy selenomethionine(OH-SeMet)linearly increased muscular Se deposition and exhibited protective effects via regulating the expression of selenotranscriptome and key selenoproteins,which was mainly reflected in lower ROS levels and higher antioxidant capacity in skeletal muscle,and the mitigation of mitochondrial dysfunction and ER stress.What’s more,selenoproteins inhibited DOS induced protein and lipid degradation and improved protein and lipid biosynthesis via regulating AKT/mTOR/S6K1 and AMPK/SREBP-1 signalling pathways in skeletal muscle.However,several parameters such as the activity of GSH-Px and T-SOD,the protein abundance of JNK2,CLPP,SELENOS and SELENOF did not show dose-dependent changes.Notably,several key selenoproteins such as MSRB1,SELENOW,SELENOM,SELENON and SELENOS play the unique roles during this protection.Conclusions Increased expression of selenoproteins by dietary OH-SeMet could synergistically alleviate mitochondrial dysfunction and ER stress,recover protein and lipid biosynthesis,thus alleviate skeletal muscle growth retardation.Our study provides preventive measure for OS-dependent skeletal muscle retardation in livestock husbandry.
基金supported by Science and Technology Programme of Shaanxi Province(2020SF-076)Science Research Project of Education Department of Shaanxi Province(19JS015)Healthcare Research Fund from Health Commission of Shaanxi Province(2018A019).
文摘Objective Iodothyronine deiodinases(DIOs)are important selenoproteins that play a key role in the bone and joint diseases.Osteoarthritis(OA)is the most prevalent joint disease especially in elders.This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis.Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques,mcluding GenCLip 3.0,Database for Annotation,Visualization and Integrated Discovery(DAVID),STRING,Cytoscape,and Network Analyst.The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus(GEO)database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3.Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine;GO analysis showed that DIOs were mainly involved in biological processes,such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling;SULT1A1 was the core node of the PPI network;miRNAs and thyroid hormones had some iterations with DIO1 and DI02;Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients(SMD=0.31,95%CI:0.03,0.59,P=0.03).Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone.And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.
基金Supported by Science and Technology Investigation and Development Project of Shaanxi Province, No. 2002K10-G1
文摘AIM: To investigate the expression of selenoprotein P mRNA (SePmRNA) in tissues of normal liver, liver cirrhosis and hepatocellular carcinoma (HCC), and its relationship with HCC occurrence and development. METHODS: The expression of SePmRNA in tissues of normal liver, liver cirrhosis and HCC were detected by in situ hybridization using a cDNA probe. RESULTS: The enzyme digesting products of PBluescript-H uman Selenoprotein P were evaluated by electrophoresis. The positive expression of SePmRNA was found in the tissues of normal liver, liver cirrhosis and HCC. The expression of SeP mRNA was found in hepatic interstitial substance, especially in endothelial cells and lymphocytes of vasculature. The positive rate of SePmRNA in normal liver tissue was 84.6% (11/13) and the positive signals appeared in the nucleus and cytoplasm, mostly in the nucleolus, and the staining granules were larger in the nucleolus and around the nucleus. The positive rate of SePmRNA in liver cirrhosis tissue was 45.0% (9/20) and the positive signals were mainly in the nucleolus and cytoplasm, being less around the nucleus and inner nucleus than that in normal liver tissue. The positive rate of SePmRNA in HCC tissue was 30.0% (9/30) and the positive signals were in the cytoplasm, but less in the nucleus. CONCLUSION: SePmRNA expression in the tissues of normal liver and HCC is significantly different (84.6% vs 30.0%, P = 0.003), suggesting that SeP might play a role in the occurrence and development of HCC.
文摘The nucleotide sequences of the open reading frames of cDNAs for selenoprotein W from skeletal muscle of rat, mouse, sheep, rhesus monkey and human are reported. Theoretical translation of the coding sequences indicated highly similar proteins of 88 (mouse and rat) or 87 (human, monkey and sheep) amino acids. In 73 of 88 positions the specified amino acids are identical for all five proteins. TGA encoding selenocysteine is the 13th codon of all the cDNAs. The rnouse, rat and sheep open reading frames terminate with TGA but the human and rhesus monkey coding regions terminate with TAA. The encoded amino acid sequences are identical for the rat and mouse proteins, and for the human and monkey proteins. The similarity of the cDNAs continues in the 3' noncoding regions through the putative selenocysteine insertion sequence (SEClS) elements which are required for correct interpretation of the selenocysteine codon. The region between the SECIS elements and the polyadenylation signals showed much lower similarity. The cloned rat gene for selenoprotein W is 5000 bases long,with the 663 bases of the cDNA in six exons. The transcription start site was identified by nuclease protection assay to be 16 bases upstream of the longest cDNA clone. A canonical TATA box occurs 150 bases upstream, but the assay did not indicate the presence of longer mRNAs
文摘Selenocysteine (Sec) tRNAs serve as carrier molecules for the biosynthesis of Sec from serine and to donate Sec to protein in response to specific UGA codons. In this study, we describe the current status of Sec tRNAs in higher animals and further we exarnine: (i) the Sec tRNA population in Drosophila; (ii) transcription of the Sec tRNA in vivo (in Xenopus oocytes) and in vitro (in Xenopus oocyte extracts); (iii) the effect of selenium on the Sec tRNA population in various rat tissues following replenishment of extremely selenium deficient rats with this element; and (iv) the biosynthesis of the modified bases on Sec tRNA in Xenopus oocytes
文摘Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect, although low molecular weight seleno-compounds have also been posited to selectively induce apoptosis in transformed cells. To address the effects of selenium supplementation on selenoprotein expression in prostate cells, we have undertaken an analysis of antioxidant selenoprotein expression as well as selenium toxicity in non-tumorigenic prostate epithelial cells （RWPE- 1 ） and prostate cancer cells （LNCaP and PC-3）. Our results show that two of the glutathione peroxidase family members （GPX1 and GPX4） are highly induced by supplemental selenium in prostate cancer cells but only slightly induced in RWPE-1 cells. In addition, GPX 1 levels are dramatically lower in PC-3 cells as compared to RWPE- 1 or LNCaP cells. GPX2 protein and mRNA, however, are only detectable in RWPE-1 cells. Of the three selenium compounds tested （sodium selenite, sodium selenate and selenomethionine）, only sodium selenite shows toxicity in a physiological range of selenium concentrations. Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells.
文摘This paper reviews some recent findings on the interactions between selenium deficiency and iodine deficency. Both micronutrients can control the levels of selenoprotein mRNAs, particularly in the thyroid and brain. When selenium and iodine supplies are limiting the compensatory mechanisms work to minimise adverse effects on thyroid hormone metabolsm and thus neurological developtnent. The mechanisms for regulation of selenoproteins in selenium and iodine deficiency are however very tissue-specific. For example, unlike the brain and thyroid,brown adipose tissue is unable to retain selenoproteins in selenium and iodine deficiency and is therefore at greater risk from injurious effects of the deficiencies.
文摘Selenium has been recognized as an essential nutrient in animals since the 1950s. Demonstration of the role of dietary selenium in protection from oxidative stress foIlowed in the early 1970s, and was largely attributed to its presence as an integral part of cellular glutathione peroxidase. However, the functions of this enzyme did not explain many of the other effects of selenium deficiency. The identification of other mammalian selenoproteins during the last few years has provided new insights into the functions of this trace nutrient. The discovery that type 1 deiodinase (D1) is a selenoenzyme, in addition to unveiling an essential role for selenium in thyroid hormone action, has had more far-reaching implications. Studies of this protein opened the door for investigation of the requirements for eukaryotic selenoprotein synthesis,and the features that distinguish this pathway from the corresponding prokaryotic pathway.Selenium is present in a number of prokaryotic and eukaryotic proteins in the form of the unusual amino acid, selenocysteine. Incorporation of selenocysteine into these proteins requires a novel translation step in which UGA specifies selenocysteine insertion. Since UGA codons are typically recognized as translation stop signals, an intriguing question is raised: How does a cell recognize and distinguish a UGA selenocysteine codon from a UGA stop codon? In this review, we will focus on what is known about selenocysteine incorporation in eukaryotes, briefly summarizing initial studies and discussing a few recent advances in our understanding of this unique 'recoding' process
文摘After labeling of rats in vivo with 75Se and protein separation by sodium dodecyl sulfatepolyacrylamide gel electrophoresis more than 25 Se-containing bands could be distinguished.Of those proteins which were detected only in certain compartments and might therefore have tissue-specific functions, two were chosen for detailed investigation.A 15 kDa-protein was found in the prostatic epithelium where it accounted for about two thirds of the protein-bound 75Se. It was mainly present in the cytosol but was not released into the prostatic secretion. After gel chromatography it was found in the fraction which contained proteins with molecular masses of about 300 kDa. Using two-dimensional electrophoresis a plvalue of about 4. 5 was determined.In the testis a specific Se-containing 34 kDa-protein was observed which appeared after the onset of puberty. It was localized in the spermatid nuclei where it contained about 80% of the Se tracer present and was found to be bound to the DNA. After extraction it partly disintegrated into a 20 kDa-protein.Both compounds contain Se in the form of selenocysteine. The fact that their formation had priority over that of glutathione peroxidase during insufficient Se intake is an indication of their biological significance. Special interest in the prostatic epithelial selenoprotein derives from a possible inverse relationship between the Se status and the incidence of prostate cancer observed in epidemiological studies, whereas with the 34 kDa-selenoprotein its appearance during the condensation phase of the spermatid nuclei might suggest its participation in some processes of sperm maturation
文摘Ebola virus infection is the present public health problem.The trend of worldwide epidemic becomes the serious consideration for this infection.The Ebola virus infection has main clinical manifestation as acute febrile illness with hemorrhagic episode.The problem of hemostatic disturbance can be seen.Focusing on the palhophysiology.selenium plays an important role in the blood clotting regulation.The study on the selenoprotein of the Ebola virus can be useful for further understanding on the pathology of the infection.Here,the authors use metallomics analysis for assessment of Ebola virus genome.According to this study,the selenoprotein portion within Ebola virus genome can be detected at position 1046-1115.
基金De La Sale University-University Research Coordination OficeUniversity Science Foundation(USF)under project#43FU/S309 and partly from the Department of Science and Technology.
文摘Objective:To investigate if the protective effect ofα-tocopherol against the impact of ethanol on brain morphogenesis involved the activity of the selenoproteins phospholipid hydroperoxide glutathione peroxidase (PHGPx;GPx4) and selenoprotein P (SelPP) that have roles against oxidative stress.Methods:Forty female mice were randomly assigned into natural control (CON), positive control (ETOH), low-, medium-, and high-α-tocopherol-supplemented-ethanol groups (LTOC, MTOC, HTOC, respectively). CON received drinking water without ethanol while ETOH, LTOC, MTOC and HTOC groups received 20% ethanol in drinking water. The supplemented groups were given respective dosages ofα-tocopherol, 0.410, 0.819, and 1.640 mg/g body weight, at day 14 before mating onwards to the day 9 of gestation. At 10.5 ED of gestation (1100 h), the pregnant females were sacrificed by cervical dislocation and the embryos were harvested. Total RNA were extracted, cDNA synthesis and qRT- PCR analyses were carried out.Results: The level of expression of PHGPx in the positive control was significantly lower than that of the natural control. Among the threeα-tocopherol-supplemented groups, only the medium dose- group was significantly higher than the positive control. The level of expression of SelPP in the positive control was significantly lower than those of the natural control, the low- and medium- dose -tocopherol supplemented groups. In the high dose-α-tocopherol supplemented group, the level of expression was not significantly different from the positive control but significantly lower than the natural control.Conclusions: The activity of the selenoproteins PHGPx and SelPP are involved in the internetwork of antioxidative enzymes with vitamin E when given up to a medium dose only and is one of the possible pathways of shielding embryonic development against the impact of ethanol on brain morphogenesis. This study strengthens the impact of dietaryα-tocopherol and Selenium supplement during the critical period of pregnancy.
基金supported by the Heilongjiang Provincial Natural Science Foundation for Outstanding Youth(No.YQ2021C021),China。
文摘The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.
基金the framework of the State assignment No.075-00607-25-00.
文摘Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to staurosporine(STS)and hyperthermia.Methods A stable SELENOM-knockdown(SELENOM-KD)cell line was created.We measured reactive oxygen species(ROS),mitochondrial membrane potential(ΔΨm),cell death,and apoptotic gene expression.Results SELENOM-KD increased basal ROS levels and induced mitochondrial dysfunction.It sensitized cells to STS-induced apoptosis,enhancing the upregulation of pro-apoptotic genes.Conversely,under hyperthermia(42°C),SELENOM-KD cells exhibited significant thermoresistance,with 52%survival vs.99%death in controls,associated with suppressed pro-apoptotic signaling.Conclusions SELENOM is a critical redox and mitochondrial regulator in GBM.Its loss produces a context-dependent effect on cell fate:sensitizing to chemical apoptosis while conferring resistance to hyperthermia.SELENOM expression is a promising predictive biomarker for stratifying GBM patients for hyperthermia-based therapies.
文摘The computer program RNA Draw was used to identify the secondary structures in the 3’untranslated regions (3’UTRs) of the mRNAs from 46 eukaryotic seleno-proteins among 7 species. The program found one or two possible SECIS elements in these selenoproteins. The SECIS element consists of a stem-loop or hairpin structure with three conserved sequences of AUGA-(A)AA-GA. SECIS element was not found by the RNA Draw program in randomly selected non-selenoproteins. The results showed that SECIS element is the unique character of the genes ofeukaryotic selenoproteins. Thus it is possible to use RNA Draw to search the SECIS elements in gene bank for potential new selenoproteins.
