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P D Whanger - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH COMMUNICATION Tissue distribution and influence of selenium status on levels of Selenoprotein W
2013Co-Authors: Jan-ying Yeh, M. A. Beilstein, J S Andrews, P D WhangerAbstract:ABSTRACT Rabbits Were immunized With tWo synthetic peptides based on hydrophilic regions of Selenoprotein W from rat muscle. The resulting polyclonal antibodies Were used in Western blots to determine the compartmentation and tissue distribution of Selenoprotein W, and to determine the influence of selenium on the levels of this Selenoprotein in rat muscle. Selenoprotein W exists mainly in cytosol, but very small amounts Were associated With membranes. Western blots revealed Selenoprotein W in muscle, spleen, testis, and brain of rats. Rats Were fed diets of either no addition of selenium (0 ppm Se) or additions of 0.1 and 4.0 mg selenium/g (0.1 ppm Se and 4.0 ppm Sc) diet for 6 Wk. Selenoprotein W Was undetectable in skeletal muscle of rats fed the basal diet, detectable in those fed 0.1 ppm selenium in the diet, and much higher in muscle from rats fed 4 ppm selenium diet. In a species comparison, Western blots indicated the presence of Selenoprotein W in muscle of rabbits, sheep, and cattle
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Selenoprotein expression and function—Selenoprotein W
Biochimica et biophysica acta, 2009Co-Authors: P D WhangerAbstract:Selenoprotein W (SeW) is a small Selenoprotein (85 to 88 amino acids) first identified in sheep suffering from selenium deficiency. The levels are highest in muscle, heart (except rodents) spleen and brain. The deduced amino acid sequence has been obtained for mice, rats, monkeys, humans, sheep, pigs, fish and chickens. The sequences of SeW are identical in rats and mice as Well as monkeys and humans. In all eight species of animals cysteine is present at residue number 9 and selenocysteine at residue number 13. Residue number 37 is cysteine in six species of animal With fish and chickens as the exceptions. Of those examined, the rodent SeW is the only one containing four cysteines Whereas the others contain only tWo cysteines. Glutathionylaltion has been shoWn for SeW from rats and monkeys but has not been confirmed for this Selenoprotein from the other six animals. The biological function of SeW has not been definitely identified. Evidence has been obtained that it can serve as an antioxidant, responds to stress, involved in cell immunity, specific target for methylmercury, and has thioredoxin-like function.
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Selenoprotein expression and function - Selenoprotein W.
Biochimica et Biophysica Acta, 2009Co-Authors: P D WhangerAbstract:Selenoprotein W (SeW) is a small Selenoprotein (85 to 88 amino acids) first identified in sheep suffering from selenium deficiency. The levels are highest in muscle, heart (except rodents) spleen and brain. The deduced amino acid sequence has been obtained for mice, rats, monkeys, humans, sheep, pigs, fish and chickens. The sequences of SeW are identical in rats and mice as Well as monkeys and humans. In all eight species of animals cysteine is present at residue number 9 and selenocysteine at residue number 13. Residue number 37 is cysteine in six species of animal With fish and chickens as the exceptions. Of those examined, the rodent SeW is the only one containing four cysteines Whereas the others contain only tWo cysteines. Glutathionylaltion has been shoWn for SeW from rats and monkeys but has not been confirmed for this Selenoprotein from the other six animals. The biological function of SeW has not been definitely identified. Evidence has been obtained that it can serve as an antioxidant, responds to stress, involved in cell immunity, specific target for methylmercury, and has thioredoxin-like function.
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deletion analysis of the rodent Selenoprotein W promoter
Journal of Inorganic Biochemistry, 2005Co-Authors: L A Hooven, L.w. Ream, William R Vorachek, A B Bauman, J A Butler, P D WhangerAbstract:To identify regulatory elements in the rat Selenoprotein W (SeW) promoter, 2090, 1265, 741, and 404 base pair truncations of genomic DNA lying immediately upstream of the SeW coding sequence Were cloned into a luciferase reporter vector (pGL3-Basic from Promega, Madison, WI, USA). 3656 and 406 base pair mouse SeW promoter constructs Were also compared. SeW promoter activity Was assayed in tWo rat cell lines: L8 muscle cells and C6 brain cells. The SeW promoter Was 2-7 times more active (p<0.01) than SV40 promoter. Promoter activity of constructs of the SeW promoter ranging from 200 base pairs to 51 base pairs gradually decreased to zero in brain cells, but fell precipitously to zero in muscle cells. Some truncations stimulated promoter activity, suggesting the full-length promoter may contain binding sites for factors that suppress SeW expression.
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identification of putative transcription factor binding sites in rodent Selenoprotein W promoter
Journal of Inorganic Biochemistry, 2004Co-Authors: A Amantana, Walt Ream, William R Vorachek, J A Butler, P D WhangerAbstract:To understand transcriptional regulation of the Selenoprotein W (SeW) gene, We used in vitro binding assays to identify transcription factors that may be involved in the transcriptional regulation of the SeW gene. Using protein from rat C6 (glial) cell nuclear extracts, oligonucleotides containing putative regulatory elements in the SeW promoter and antibodies, We observed that specificity protein 1(Sp1) transcription factor binds to the Sp1 consensus sequence in the SeW promoter as Well as to the metal response element (MRE). Although competition analysis shoWed specific binding at the TFII-1 site, super-shift analysis using anti-TFII-1 antibody did not yield any super-shifted band. Therefore, the SeW gene may be a target for Sp1 Whose binding to various regulatory sequences of the SeW promoter may activate or repress the transcription of SeW. The MRE, GRE, AP-1 and LF-A1 sites Were also tested but no evidence Was obtained for specific binding as indicated by lack of competition With unlabeled probes.
Ziwei Zhang - One of the best experts on this subject based on the ideXlab platform.
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Analysis of the Interactions BetWeen Thioredoxin and 20 Selenoproteins in Chicken
Biological Trace Element Research, 2017Co-Authors: Jie Yang, Hamid Sattar, Yilin Luan, Shiwen Xu, Ziwei ZhangAbstract:Thioredoxin (Trx) is a small molecular protein With complicated functions in a number of processes, including inflammation, apoptosis, embryogenesis, cardiovascular disease, and redox regulation. Some Selenoproteins, such as glutathione peroxidase (Gpx), iodothyronine deiodinase (Dio), and thioredoxin reductase (TR), are involved in redox regulation. HoWever, Whether there are interactions betWeen Trx and Selenoproteins is still not knoWn. In the present paper, We used a Modeller, Hex 8.0.0, and the KFC2 Server to predict the interactions betWeen Trx and Selenoproteins. We used the Modeller to predict the target protein in objective format and assess the accuracy of the results. Molecular interaction studies With Trx and Selenoproteins Were performed using the molecular docking tools in Hex 8.0.0. Next, We used the KFC2 Server to further test the protein binding sites. In addition to the Selenoprotein physiological functions, We also explored potential relationships betWeen Trx and Selenoproteins beyond all the results We got. The results demonstrate that Trx has the potential to interact With 19 Selenoproteins, including iodothyronine deiodinase 1 (Dio1), iodothyronine deiodinase 3 (Dio3), glutathione peroxidase 1 (Gpx1), glutathione peroxidase 2 (Gpx2), glutathione peroxidase 3 (Gpx3), glutathione peroxidase 4 (Gpx4), Selenoprotein H (SelH), Selenoprotein I (SelI), Selenoprotein M (SelM), Selenoprotein N (SelN), Selenoprotein T (SelT), Selenoprotein U (SelU), Selenoprotein W (SelW), Selenoprotein 15 (Sep15), methionine sulfoxide reductase B (Sepx1), selenophosphate synthetase 1 (SPS1), TR1, TR2, and TR3, among Which TR1, TR2, TR3, SPS1, Sep15, SelN, SelM, SelI, Gpx2, Gpx3, Gpx4, and Dio3 exhibited intense correlations With Trx. HoWever, additional experiments are needed to verify them.
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Selenoprotein W redox regulated ca 2 channels correlate With selenium deficiency induced muscles ca 2 leak
Oncotarget, 2016Co-Authors: Haidong Yao, Wenchao Zhao, Hamid Sattar, Jie Yang, Xia Zhao, Ruifeng Fan, Wei Liu, Jinxin Zhao, Ziwei ZhangAbstract:// Haidong Yao 1,* , Ruifeng Fan 1,* , Xia Zhao 1 , Wenchao Zhao 1 , Wei Liu 1,2 , Jie Yang 1 , Hamid Sattar 1 , Jinxin Zhao 1 , ZiWei Zhang 1 and ShiWen Xu 1 1 Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China 2 The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, P. R. China * These authors have contributed equally to this Work Correspondence to: ShiWen Xu, email: // ZiWei Zhang, email: // KeyWords : selenium deficiency; Ca2+ leak; Selenoprotein W; Ca 2+ channels; redox regulation Received : June 11, 2016 Accepted : August 17, 2016 Published : August 20, 2016 Abstract Selenium (Se) deficiency induces Ca 2+ leak and calcification in mammal skeletal muscles; hoWever, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and Selenoprotein W (SelW) gene knockdoWn myoblast and embryo models Were used to study the mechanism. The results shoWed that Se deficiency-induced typical muscular injuries accompanied With Ca 2+ leak and oxidative stress ( P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca 2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 ( P < 0.05); and increased the levels of Ca 2+ channel PMCA ( P < 0.05). Similarly, SelW knockdoWn also induced Ca 2+ leak from the SR and cytoplasm; increased mitochondrial Ca 2+ levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca 2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdoWn induced Ca 2+ leak, oxidative stress, and Ca 2+ channel reduction. In addition, Ca 2+ levels and the expression of the Ca 2+ channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 Were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared With SelW knockdoWn cells. Thus, With regard to the decreased Ca 2+ channels, SelW knockdoWn closely correlated Se deficiency With Ca 2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca 2+ leak in muscles.
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Selenoprotein W Was correlated With the protective effect of selenium on chicken myocardial cells from oxidative damage
Biological Trace Element Research, 2016Co-Authors: Wenchao Zhao, Haidong Yao, Wei Liu, Yuguang Shi, Ziwei ZhangAbstract:Selenium (Se) mainly performs its function through Se-containing proteins. Selenoprotein W (SelW), one member of the Selenoprotein family, plays important roles in the normal function of the heart. To investigate the possible relationship betWeen Se and SelW for the regulation of oxidative damage in chicken embryo myocardial cells, We treated myocardial cells With Se and H2O2. Then, the levels of lactate dehydrogenase (LDH) and 3,4-methylenedioxyamphetamine in the culture media, levels of SelW, inflammatory genes NF-κB, tumor necrosis factor (TNF)-α, p53, and the cell cycle Were analyzed. Furthermore, the correlation betWeen SelW and the levels of these factors Was determined. The results indicated that Se treatment increased the expression of SelW (P < 0.05) and caused a doWnregulation of p53, NF-κB, and TNF-α (P < 0.05). In contrast, H2O2 increased the expression of p53, NF-κB, TNF-α, and LDH (P < 0.05) and induced early cell apoptosis, Which Was alleviated by treatment With Se. In addition, SelW had a positive correlation With the levels of inflammatory genes investigated. Taken together, our findings suggested that SelW is sensitive to Se levels and oxidative stress, and may play a role in the protective function of Se against oxidative damage and inflammation in chicken myocardial cells.
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the role of Selenoprotein W in inflammatory injury in chicken immune tissues and cultured splenic lymphocyte
Biometals, 2015Co-Authors: Ziwei Zhang, Haidong YaoAbstract:Selenoprotein W (SelW) is mainly understood in terms of its antioxidant effects in the cellular defense system. Inflammation is an important indicator of animal tissue injury, and the inflammatory cells may trigger a sophisticated and Well-orchestrated inflammatory cascade, resulting in exaggerated oxidative stress. To investigate the role of SelW in inflammatory injury in chicken immune tissues and cultured splenic lymphocyte, in this report, the effects of selenium (Se) on mRNA expressions of SelW and inflammatory factors (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in the chicken immune organs (spleen, thymus and bursa of Fabricius) and cultured splenic lymphocyte treated With sodium selenite and H2O2, or knocked doWn SelW With small interfering RNAs (siRNAs) Were examined. The results shoWed that Se-deficient diets effectively decreased the mRNA expression of SelW (P < 0.05), and induced a significantly up-regulation of COX-2, iNOS, NF-κB, PTGEs and TNF-α mRNA levels (P < 0.05). The histopathological analysis shoWed that immune tissues Were obviously injured in the loW-Se groups. In vitro, H2O2 induced a significantly up-regulation of the mRNA levels of inflammation-related genes (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in cultured splenic lymphocyte (P < 0.05). When lymphocytes Were pretreated With Se before treated With H2O2, the inflammation-related genes Were significantly decreased (P < 0.05). Silencing of SelW significantly up-regulated the inflammation-related genes (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in cultured splenic lymphocyte (P < 0.05). The results suggested that the expression levels of inflammatory factors (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) and SelW can be influenced by Se in birds. SelW commonly played an important role in the protection of immune organs of birds from inflammatory injury by the regulations of inflammation-related genes.
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Different responses of Selenoproteins to the altered expression of Selenoprotein W in chicken myoblasts
RSC Advances, 2014Co-Authors: Wenchao Zhao, Pervez Ahmed Khoso, Ziwei Zhang, Xia Zhao, Shiwen XuAbstract:The aim of the present study Was to examine the role of Selenoprotein W (SepW1) in modulating the expression of other Selenoproteins. In the present study, We silenced and overexpressed the expression of SepW1 in chicken myoblasts and subsequently treated the myoblasts With a reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), and H2O2. Thereafter, the levels of expression of 25 Selenoproteins and the activities of certain antioxidative enzymes, glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) Were analyzed. In addition, principal component analysis (PCA) Was used to define the most important parameters that could be used as key factors. The results indicated that as a highly expressed Selenoprotein (only loWer than Gpx1, Selk, Sels and Sep15), SepW1 could interact With H2O2 (P < 0.05) and influence the expression of some Selenoproteins (Gpx3, Gpx4, Txnrd1, Selt, Selh, Sepp1, Sels and Sep15, P < 0.05) and the sensitivity of the cells to H2O2. Both the overexpression and silencing of SepW1 influenced the mRNA levels of Selenoproteins. HoWever, the responses of Selenoproteins to altered SepW1 expression Were different. The results indicated that SepW1 played a special role in H2O2 metabolism and may modulate the expression of certain Selenoproteins through the redox pathWay. Therefore, these results indicate that SepW1 is an essential antioxidative Selenoprotein in chicken myoblasts.
Wayne Chris Hawkes - One of the best experts on this subject based on the ideXlab platform.
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Selenoprotein W controls epidermal groWth factor receptor surface expression activation and degradation via receptor ubiquitination
Biochimica et Biophysica Acta, 2015Co-Authors: Zeynep Alkan, Frank Duong, Wayne Chris HawkesAbstract:Abstract Epidermal groWth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of groWth factor receptors that modulate a complex netWork of intracellular signaling pathWays controlling groWth, proliferation, differentiation, and motility. Selenoprotein W (SEPW1) is a highly conserved, diet-regulated 9 kDa thioredoxin-like protein required for normal cell cycle progression. We report here that SEPW1 is required for EGF-induced EGFR activation and that it functions by suppressing EGFR ubiquitination and receptor degradation. SEPW1 depletion inhibited EGF-dependent cell cycle entry in breast and prostate epithelial cells. In prostate cells, SEPW1 depletion decreased EGFR auto-phosphorylation, While SEPW1 overexpression increased EGFR auto-phosphorylation. SEPW1 depletion increased the rate of EGFR degradation, Which decreased total and surface EGFR and suppressed EGF-dependent EGFR endocytosis, EGFR dimer formation, and activation of EGF-dependent pathWays. EGFR ubiquitination Was increased in SEPW1-depleted cells — in agreement With the increased rate of EGFR degradation, and suggests that SEPW1 suppresses EGFR ubiquitination. Ubiquitination-directed lysozomal degradation controls post-translational EGFR expression and is dysregulated in many cancers. Thus, suppression of EGFR ubiquitination by SEPW1 may be related to the putative increase in cancer risk associated With high selenium intakes. KnoWledge of the mechanisms underlying SEPW1's regulation of EGFR ubiquitination may reveal neW opportunities for nutritional cancer prevention or cancer drug development.
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Selenoprotein W inhibits the c met oncogene by regulating receptor ubiquitination
The FASEB Journal, 2015Co-Authors: Christina Wilcox, Zeynep Alkan, Wayne Chris HawkesAbstract:Background: Hepatocyte GroWth Factor Receptor (HGFR), or c-Met, is the receptor for Hepatocyte GroWth Factor (HGF). HGF-bound c-Met causes the activation of many important doWnstream pathWays leading to cell proliferation, survival, invasion, differentiation, and migration. Selenoprotein W1 (SEPW1) is a selenium (Se) regulated, small thioredoxin-like protein required for cell cycle entry in breast and prostate epithelial cells. Se is an essential micronutrient With an involvement in cancer, but the mechanisms of its action are unclear. LoW levels of dietary Se can be a risk factor for many cancers including liver cancer. The objective of this study Was to investigate the mechanisms by Which SEPW1 inhibits the invasive properties of hepatocellular carcinoma in HepG2 cells. Results: Silencing SEPW1 caused an increase in total c-Met expression, c-Met located on the plasma membrane, and HGF-induced c-Met phosphorylation in HepG2 human hepatocellular carcinoma cells. Consistent With the increase in total c-Met...
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Selenoprotein W regulates epidermal groWth factor receptor trafficking expression and activation 374 4
The FASEB Journal, 2014Co-Authors: Wayne Chris Hawkes, Zeynep Alkan, Frank Duong, Priya RanganAbstract:Epidermal groWth factor (EGF) receptor (EGFR) is the founding member of the ErbB family of groWth factor receptors that control groWth, proliferation, differentiation, apoptosis, and cell migration. Selenoprotein W (SEPW1) is a highly conserved, ubiquitously expressed 9 kDa selenocysteine-containing protein involved in cell cycle control. SEPW1 siRNA inhibited EGFR activation in RWPE-1, MCF-10A and MCF-7 cells, While SEPW1 overexpression increased it. SEPW1 siRNA inhibited EGF-induced activation of doWnstream pathWays (MAPK, PI3K/Akt, JAK/STAT, and p53), and blocked EGF-induced cell cycle entry. SEPW1 Was associated With peripheral punctuate structures that partially co-localized With EGFR. Ligand-bound EGFR failed to traffic toWards the nucleus in SEPW1-depleted cells, indicating that SEPW1 has a role in EGFR trafficking. Consequently, the half-life, expression, dimerization, and phosphorylation of EGFR Were also decreased in SEPW1-depleted cells. SEPW1 siRNA also inhibited hydrogen peroxide-induced EGFR...
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delayed cell cycle progression in Selenoprotein W depleted cells is regulated by a mitogen activated protein kinase kinase 4 p38 c jun nh2 terminal kinase p53 pathWay
Journal of Biological Chemistry, 2012Co-Authors: Wayne Chris Hawkes, Zeynep AlkanAbstract:Selenoprotein W (SEPW1) is a ubiquitous, highly conserved thioredoxin-like protein Whose depletion causes a transient p53- and p21Cip1-dependent G1-phase cell cycle arrest in breast and prostate epithelial cells. SEPW1 depletion increases phosphorylation of Ser-33 in p53, Which is associated With decreased p53 ubiquitination and stabilization of p53. We report here that delayed cell cycle progression, Ser-33 phosphorylation, and p53 nuclear accumulation from SEPW1 depletion require mitogen-activated protein kinase kinase 4 (MKK4). Silencing MKK4 rescued G1 arrest, Ser-33 phosphorylation, and nuclear accumulation of p53 induced by SEPW1 depletion, but silencing MKK3, MKK6, or MKK7 did not. SEPW1 silencing did not change the phosphorylation state of MKK4 but increased total MKK4 protein. Silencing p38γ, p38δ, or JNK2 partially rescued G1 arrest from SEPW1 silencing, suggesting they signal doWnstream from MKK4. These results imply that SEPW1 silencing increases MKK4, Which activates p38γ, p38δ, and JNK2 to phosphorylate p53 on Ser-33 and cause a transient G1 arrest.
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Selenoprotein W depletion induces a p53 and p21 dependent delay in cell cycle progression in rWpe 1 prostate epithelial cells
Journal of Cellular Biochemistry, 2012Co-Authors: Wayne Chris Hawkes, Ignat Printsev, Zeynep AlkanAbstract:The anticancer activity of selenium (Se) has been demonstrated in myriad animal and in vitro studies, yet the mechanisms remain obscure. The main form of Se in animal tissues is selenocysteine in Selenoproteins, but the relative importance of Selenoproteins versus smaller Se compounds in cancer protection is unresolved. Selenoprotein W (SEPW1) is a highly conserved protein ubiquitously expressed in animals, bacteria, and archaea. SEPW1 depletion causes a delay in cell cycle progression at the G1/S transition of the cell cycle in breast and prostate epithelial cells. Tumor suppressor protein p53 is a master regulator of cell cycle progression and is the most frequently mutated gene in human cancers. p53 Was increased in SEPW1 silenced cells and Was inversely correlated With SEPW1 mRNA in cell lines With altered SEPW1 expression. Silencing SEPW1 decreased ubiquitination of p53 and increased p53 half-life. SEPW1 silencing increased p21(Cip1/WAF1/CDKN1A), While p27 (Kip1/CDKN1B) levels Were unaffected. G1-phase arrest from SEPW1 knockdoWn Was abolished by silencing p53 or p21. Cell cycle arrest from SEPW1 silencing Was not associated With activation of ATM or phosphorylation of Ser-15 in p53, suggesting the DNA damage response pathWay Was not involved. Silencing GPX1 had no effect on cell cycle, suggesting that G1-phase arrest from SEPW1 silencing Was not due to loss of antioxidant protection. More research is required to identify the function of SEPW1 and hoW it affects stability of p53. J. Cell. Biochem. 113: 61–69, 2012. © 2011 Wiley Periodicals, Inc.
Haidong Yao - One of the best experts on this subject based on the ideXlab platform.
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Selenoprotein W redox regulated ca 2 channels correlate With selenium deficiency induced muscles ca 2 leak
Oncotarget, 2016Co-Authors: Haidong Yao, Wenchao Zhao, Hamid Sattar, Jie Yang, Xia Zhao, Ruifeng Fan, Wei Liu, Jinxin Zhao, Ziwei ZhangAbstract:// Haidong Yao 1,* , Ruifeng Fan 1,* , Xia Zhao 1 , Wenchao Zhao 1 , Wei Liu 1,2 , Jie Yang 1 , Hamid Sattar 1 , Jinxin Zhao 1 , ZiWei Zhang 1 and ShiWen Xu 1 1 Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China 2 The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, P. R. China * These authors have contributed equally to this Work Correspondence to: ShiWen Xu, email: // ZiWei Zhang, email: // KeyWords : selenium deficiency; Ca2+ leak; Selenoprotein W; Ca 2+ channels; redox regulation Received : June 11, 2016 Accepted : August 17, 2016 Published : August 20, 2016 Abstract Selenium (Se) deficiency induces Ca 2+ leak and calcification in mammal skeletal muscles; hoWever, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and Selenoprotein W (SelW) gene knockdoWn myoblast and embryo models Were used to study the mechanism. The results shoWed that Se deficiency-induced typical muscular injuries accompanied With Ca 2+ leak and oxidative stress ( P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca 2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 ( P < 0.05); and increased the levels of Ca 2+ channel PMCA ( P < 0.05). Similarly, SelW knockdoWn also induced Ca 2+ leak from the SR and cytoplasm; increased mitochondrial Ca 2+ levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca 2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdoWn induced Ca 2+ leak, oxidative stress, and Ca 2+ channel reduction. In addition, Ca 2+ levels and the expression of the Ca 2+ channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 Were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared With SelW knockdoWn cells. Thus, With regard to the decreased Ca 2+ channels, SelW knockdoWn closely correlated Se deficiency With Ca 2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca 2+ leak in muscles.
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Selenoprotein W Was correlated With the protective effect of selenium on chicken myocardial cells from oxidative damage
Biological Trace Element Research, 2016Co-Authors: Wenchao Zhao, Haidong Yao, Wei Liu, Yuguang Shi, Ziwei ZhangAbstract:Selenium (Se) mainly performs its function through Se-containing proteins. Selenoprotein W (SelW), one member of the Selenoprotein family, plays important roles in the normal function of the heart. To investigate the possible relationship betWeen Se and SelW for the regulation of oxidative damage in chicken embryo myocardial cells, We treated myocardial cells With Se and H2O2. Then, the levels of lactate dehydrogenase (LDH) and 3,4-methylenedioxyamphetamine in the culture media, levels of SelW, inflammatory genes NF-κB, tumor necrosis factor (TNF)-α, p53, and the cell cycle Were analyzed. Furthermore, the correlation betWeen SelW and the levels of these factors Was determined. The results indicated that Se treatment increased the expression of SelW (P < 0.05) and caused a doWnregulation of p53, NF-κB, and TNF-α (P < 0.05). In contrast, H2O2 increased the expression of p53, NF-κB, TNF-α, and LDH (P < 0.05) and induced early cell apoptosis, Which Was alleviated by treatment With Se. In addition, SelW had a positive correlation With the levels of inflammatory genes investigated. Taken together, our findings suggested that SelW is sensitive to Se levels and oxidative stress, and may play a role in the protective function of Se against oxidative damage and inflammation in chicken myocardial cells.
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the role of Selenoprotein W in inflammatory injury in chicken immune tissues and cultured splenic lymphocyte
Biometals, 2015Co-Authors: Ziwei Zhang, Haidong YaoAbstract:Selenoprotein W (SelW) is mainly understood in terms of its antioxidant effects in the cellular defense system. Inflammation is an important indicator of animal tissue injury, and the inflammatory cells may trigger a sophisticated and Well-orchestrated inflammatory cascade, resulting in exaggerated oxidative stress. To investigate the role of SelW in inflammatory injury in chicken immune tissues and cultured splenic lymphocyte, in this report, the effects of selenium (Se) on mRNA expressions of SelW and inflammatory factors (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in the chicken immune organs (spleen, thymus and bursa of Fabricius) and cultured splenic lymphocyte treated With sodium selenite and H2O2, or knocked doWn SelW With small interfering RNAs (siRNAs) Were examined. The results shoWed that Se-deficient diets effectively decreased the mRNA expression of SelW (P < 0.05), and induced a significantly up-regulation of COX-2, iNOS, NF-κB, PTGEs and TNF-α mRNA levels (P < 0.05). The histopathological analysis shoWed that immune tissues Were obviously injured in the loW-Se groups. In vitro, H2O2 induced a significantly up-regulation of the mRNA levels of inflammation-related genes (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in cultured splenic lymphocyte (P < 0.05). When lymphocytes Were pretreated With Se before treated With H2O2, the inflammation-related genes Were significantly decreased (P < 0.05). Silencing of SelW significantly up-regulated the inflammation-related genes (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) in cultured splenic lymphocyte (P < 0.05). The results suggested that the expression levels of inflammatory factors (iNOS, COX-2, NF-κB, PTGEs, and TNF-α) and SelW can be influenced by Se in birds. SelW commonly played an important role in the protection of immune organs of birds from inflammatory injury by the regulations of inflammation-related genes.
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possible correlation of Selenoprotein W With inflammation factors in chicken skeletal muscles
Biological Trace Element Research, 2014Co-Authors: Haidong Yao, Ziwei Zhang, Siran Tan, Yaohong ZhuAbstract:The aim of the present study Was to investigate the possible correlation of Selenoprotein W (SelW) With inflammatory injury induced by dietary selenium (Se) deficiency in chicken. One-day-old male chickens Were fed either a commercial diet or a Se-deficient diet for 55 days. Then, the expression levels of SelW messenger RNA (mRNA) and inflammation-related genes (NF-κB, TNF-α, iNOS, COX-2, and PTGES) in chicken skeletal muscles (Wing muscle, pectoral muscle, and thigh muscle) Were determined at 15, 25, 35, 45, and 55 days old, respectively. In addition, the correlation betWeen SelW mRNA expression and inflammation-related genes Were assessed. The results shoWed that dietary Se deficiency reduced the mRNA expression of SelW in chicken Wing, pectorals, and thigh muscles. In contrast, Se deficiency increased the mRNA expression levels of inflammation-related genes in chicken skeletal muscle tissues at different time points. The Pearson’s correlation coefficients shoWed that the mRNA expression levels of inflammation-related genes Were significantly negative related to SelW (p < 0.05). These data shoWed that Se deficiency induced the inflammatory response in chicken skeletal muscle. As one important Selenoprotein gene in skeletal muscles, SelW may play a role in the regulation of inflammation reaction in Se-deficiency myopathy.
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antioxidative role of Selenoprotein W in oxidant induced chicken splenic lymphocyte death
Biometals, 2014Co-Authors: Ziwei Zhang, Haidong YaoAbstract:To verify the antioxidative role of SelW in oxidant-induced chicken splenic lymphocyte, in this report, the influence of selenite supplementation and SelW gene silence on H2O2-mediated cell viability and cell apoptosis in cultured splenic lymphocyte derived from spleen of chicken Were examined. The cultured cells Were treated With sodium selenite and H2O2, or knocked doWn SelW With small interfering RNAs (siRNAs). The lymphocytes Were examined for cell viability, cell apoptosis and mRNA expression levels of SelW and apoptosis-related genes (Bcl-2, Bax, Bak-1, caspase-3 and p53). The results shoW that the mRNA expression of SelW Were effectively increased after treatment With sodium selenite, and H2O2-induced cell apoptosis Was significantly decreased and cell viability Was significantly increased. 20 μM H2O2 Was found to induce cell apoptosis and decrease cell viability, Which Was alleviated obviously When cells Were pretreated With sodium selenite before exposure to 20 μM H2O2. MeanWhile, H2O2 induced a significantly up-regulation of the Bax/Bcl-2 ratio, Bax, Bak-1, caspase-3 and p53 and doWn-regulation of Bcl-2 (P < 0.05). When lymphocytes Were pretreated With Se before treated With H2O2, the Bax/Bcl-2 ratio and mRNA expression of those genes Were significantly decreased, and Bcl-2 Was increased (P < 0.05). SelW siRNA-transfected cells Were more sensitive to the oxidative stress induced by treatment of H2O2 than control cells. Silencing of the lymphocyte SelW gene decreased their cell viability, and increased their apoptosis rate and susceptibility to H2O2. Silencing of SelW significantly up-regulated the Bax/Bcl-2 ratio, Bax, Bak-1, caspase-3 and p53 and doWn-regulated Bcl-2 (P < 0.05). The present study demonstrates that SelW plays an important role in protection of splenic lymphocyte of birds from oxidative stress.
Jan-ying Yeh - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH COMMUNICATION Tissue distribution and influence of selenium status on levels of Selenoprotein W
2013Co-Authors: Jan-ying Yeh, M. A. Beilstein, J S Andrews, P D WhangerAbstract:ABSTRACT Rabbits Were immunized With tWo synthetic peptides based on hydrophilic regions of Selenoprotein W from rat muscle. The resulting polyclonal antibodies Were used in Western blots to determine the compartmentation and tissue distribution of Selenoprotein W, and to determine the influence of selenium on the levels of this Selenoprotein in rat muscle. Selenoprotein W exists mainly in cytosol, but very small amounts Were associated With membranes. Western blots revealed Selenoprotein W in muscle, spleen, testis, and brain of rats. Rats Were fed diets of either no addition of selenium (0 ppm Se) or additions of 0.1 and 4.0 mg selenium/g (0.1 ppm Se and 4.0 ppm Sc) diet for 6 Wk. Selenoprotein W Was undetectable in skeletal muscle of rats fed the basal diet, detectable in those fed 0.1 ppm selenium in the diet, and much higher in muscle from rats fed 4 ppm selenium diet. In a species comparison, Western blots indicated the presence of Selenoprotein W in muscle of rabbits, sheep, and cattle
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Characterization and expression of chicken Selenoprotein W
BioMetals, 2011Co-Authors: Mei-jung Jiang, Chao-hsiang Lin, Yu-chuan Liang, Kuei-jen Lee, Jan-ying YehAbstract:As an essential trace element, selenium (Se) deficiency results in White Muscle Disease in livestock and Keshan disease in humans. The main objectives of this study Were to clone and characterize the chicken Selenoprotein W (SeW) gene and investigate SeW mRNA expression in chicken tissues. The deduced amino acid (AA) sequence of chicken SeW contains 85 AAs With UAG as the stop codon. Like all SeW genes identified in different species, chicken SeW contains one Well-conserved selenocysteine (Sec) at the 13th position encoded by the UGA codon. The proposed glutathione (GSH)-binding site at the Cys_37 of SeW is not conserved in the chicken, but Cys_9 and Sec_13, With possible GSH binding, are conserved in SeWs identified from all species. There are 23–59% and 50–61% homology in cDNA and deduced AA sequences of SeW, respectively, betWeen the chicken and other species. The predicted secondary structure of chicken SeW mRNA indicates that the selenocysteine insertion sequence element is type II With invariant adenosines Within the apical bulge. The SeW mRNA expression is high in skeletal muscle folloWed by brain, but extremely loW in other tissues from chickens fed a commercial maize-based diet. The SeW gene is ubiquitously expressed in heart, skeletal muscle, brain, testis, spleen, kidney, lung, liver, stomach and pancreas in chickens fed a commercial diet supplemented With sodium selenite. These results indicate that dietary selenium supplementation regulates SeW gene expression in the chicken and skeletal muscle is the most responsive tissue When dietary Se content is loW.
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effect of dietary selenium on Selenoprotein W and glutathione peroxidase in 28 tissues of the rat
Journal of Nutritional Biochemistry, 1998Co-Authors: Y. Sun, Jan-ying Yeh, J A Butler, P D WhangerAbstract:Abstract The influence of deficient (0.004 μg/g), adequate (0.1 μg/g), and excessive (4.0 μg/g) levels of dietary selenium (Se) on the Selenoprotein W (Se-W) content and glutathione peroxidase (GPX) activity Was investigated in 28 tissues of the rat. GPX activity Was found in all 28 tissues examined, and dietary selenium resulted in increased activities in all tissues, except for the spinal cord. Except for the brain, 0.1 μg Se per g diet resulted in significantly greater GPX activity in all tissues as compared With rats fed the deficient diet. When 4.0 μg Se per g diet Was fed, hoWever, this resulted in significantly greater activity in the brain as compared With the rats fed the deficient diet. Se-W Was nondetectable in liver, thyroid, pancreas, pituitary, and eyes regardless of the level of Se fed. Se-W Was not detected in heart, lungs, prostate, esophagus, small intestine, tongue, skin, diaphragm, and skeletal muscle from Se-deficient rats, but Was present in these tissues When the tWo higher levels of Se Were fed. In other tissues such as the kidney and seminal vesicles Se-W Was detected only in rats fed 4.0 μg Se per g diet. These results indicate that the distribution of Se-W among rat tissues is more Widespread than thought, and suggest that the regulation of Se-W by Se is markedly different betWeen various tissues.
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dietary selenium increases Selenoprotein W levels in rat tissues
Journal of Nutrition, 1997Co-Authors: Jan-ying Yeh, S C Vendeland, J A Butler, P D WhangerAbstract:TWo experiments Were conducted to evaluate the influence of dietary selenium (Se) on tissue levels of Selenoprotein W (Se-W) in rats. Se dependent glutathione peroxidase (GPX) activity and Se levels Were also determined for comparative measurements. In the first experiment, rats Were fed a basal diet deficient in Se or supplemented With either 0.1 or 4.0 mg Se (as selenite) per kg diet for 6 Wk. Se-W levels Were significantly higher in muscle, spleen and testes of rats fed 0.1 mg Se per kg diet compared to those fed the deficient diet (controls), and those fed 4.0 mg Se per kg diet had significantly higher levels in muscle, brain and spleen (P < 0. 05) than those fed 0.1 mg Se per kg diet. No further increases, hoWever, occurred in the tests. There Was a significant increase (P < 0.05) of mRNA encoding Se-W in muscle With each increase of dietary Se. In the second experiment rats Were fed the basal diet or this diet plus 0.01, 0.03, 0.06, 0.1, 1.0, 2.0 or 4.0 mg Se per kg diet. The levels of Se-W in muscle did not increase (P < 0.05) until 0.06 mg Se per kg diet Were fed to rats. A very marked increase (P < 0.05) occurred When 1.0 mg Se per kg diet Was fed With no further increases With higher levels. There Was a linear increase of Se-W in brain (r = 0.89) and spleen (r = 0.98) With the Se concentration in the diet up to 0.1 mg Se per kg Where a plateau Was reached. The testes shoWed a different pattern in that a very marked increase (P < 0.01) occurred When only 0.01 mg Se per kg diet Was fed Where an inflection Was reached. Except for muscle, GPX activities reached a plateau in all tissues When diets containing 0.06 to 0.1 mg supplemental Se per kg Were fed. The Se concentration in these tissues increased at a linear rate With the Se concentration in the diets up to 0.1 mg Se per kg Where it continued to rise at a different rate. The results indicate that in rats, the regulation of Se-W by Se is different for various tissues and differs from that for GPX.
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Selenium Influences Tissue Levels of Selenoprotein W in Sheep
The Journal of nutrition, 1997Co-Authors: Jan-ying Yeh, M. A. Beilstein, Neil E. Forsberg, Philip D. WhangerAbstract:Because selenium increases the levels of other Selenoproteins, the influence of this element on Selenoprotein W Was examined in Wether sheep fed either a loW selenium diet (0.02 mg/kg) or the same diet supplemented With 3 mg selenium as selenite per kilogram diet. Muscle biopsies Were taken initially and at 3.5, 7.0 and 10.5 Wk. The sheep Were killed after the last muscle biopsy and samples from nine tissues Were taken. Selenoprotein W Was determined in tissues by Western blots With a polyclonal antibody against a synthetic peptide based on the protein sequence of the homologous rat Selenoprotein W. In supplemented sheep, muscle Selenoprotein W Was significantly increased over initial levels (P < 0.05) at 7 Wk and afterWards, Whereas in sheep consuming the loW selenium diet, muscle Selenoprotein W levels declined significantly (P < 0.05) after 10.5 Wk. This Selenoprotein Was found in various amounts in all tissues examined. The highest levels of Selenoprotein W Were found in skeletal muscles and heart and the loWest Was found in liver. Except for Selenoprotein W in brain, the concentrations of Selenoprotein W, selenium and glutathione peroxidase activity Were significantly higher (P < 0.05) in all tissues from supplemented sheep than in those from unsupplemented sheep. The Selenoprotein W levels in brains of the tWo groups Were not significantly different. Thus, Selenoprotein W levels in all tissues of sheep except the brain are sensitive to selenium status.