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Henry A Spiller
INTRODUCTION: There is increasing evidence that the pathophysiological target of mercury is in fact selenium, rather than the covalent binding of mercury to sulfur in the body's ubiquitous sulfhydryl groups. The role of selenium in mercury poisoning is multifaceted, bidirectional, and central to understanding the target organ toxicity of mercury. METHODS: An initial search was performed using Medline/PubMed, Toxline, Google Scholar, and Google for published work on mercury and selenium...
November 10, 2017: Clinical Toxicology
David Wright, Zaid Altaany, Yumin Bi, Zaccary Alperstein, Patrick O'Donoghue
TrxR1 is a cancer target and essential selenoprotein that defends the cell against reactive oxygen species and regulates cellular signaling and redox pathways. Previous cell-based studies correlated TrxR1 acetylation with modulated cellular reduction activity, yet the function of specific acetylation sites on TrxR1 remain unknown. We produced site-specifically acetylated TrxR1 variants that also contain selenocysteine (Sec). We demonstrated efficient high-fidelity protein synthesis with 22 different amino acids by simultaneous UAG codon reassignment to Nε-acetyl-lysine (acK) and UGA codon recoding to Sec...
November 8, 2017: Antioxidants & Redox Signaling
Kathleen N McAllister, Laurent Bouillaut, Jennifer N Kahn, William T Self, Joseph A Sorg
Clostridium difficile is a significant concern as a nosocomial pathogen, and genetic tools are important when analyzing the physiology of such organisms so that the underlying physiology/pathogenesis of the organisms can be studied. Here, we used TargeTron to investigate the role of selenoproteins in C. difficile Stickland metabolism and found that a TargeTron insertion into selD, encoding the selenophosphate synthetase that is essential for the specific incorporation of selenium into selenoproteins, results in a significant growth defect and a global loss of selenium incorporation...
November 7, 2017: Scientific Reports
Christine C Winterbourn
Hydrogen peroxide is a generated in numerous biological processes. It transmits cellular signals, contributes to oxidative folding of exported proteins, and in excess can be damaging to cells and tissues. Although a strong oxidant, high activation energy barriers make it unreactive with most biological molecules. Its main reactions are with transition metal centers, selenoproteins and selected thiol proteins, with glutathione peroxidases and peroxiredoxins being major targets. It reacts slowly with most thiol proteins and how they become oxidized during redox signal transmission is not well understood...
November 7, 2017: Antioxidants & Redox Signaling
Daniel H Haft, Michael DiCuccio, Azat Badretdin, Vyacheslav Brover, Vyacheslav Chetvernin, Kathleen O'Neill, Wenjun Li, Farideh Chitsaz, Myra K Derbyshire, Noreen R Gonzales, Marc Gwadz, Fu Lu, Gabriele H Marchler, James S Song, Narmada Thanki, Roxanne A Yamashita, Chanjuan Zheng, Françoise Thibaud-Nissen, Lewis Y Geer, Aron Marchler-Bauer, Kim D Pruitt
The Reference Sequence (RefSeq) project at the National Center for Biotechnology Information (NCBI) provides annotation for over 95 000 prokaryotic genomes that meet standards for sequence quality, completeness, and freedom from contamination. Genomes are annotated by a single Prokaryotic Genome Annotation Pipeline (PGAP) to provide users with a resource that is as consistent and accurate as possible. Notable recent changes include the development of a hierarchical evidence scheme, a new focus on curating annotation evidence sources, the addition and curation of protein profile hidden Markov models (HMMs), release of an updated pipeline (PGAP-4), and comprehensive re-annotation of RefSeq prokaryotic genomes...
November 3, 2017: Nucleic Acids Research
E G Varlamova, M V Goltyaev, V I Novoselov, E E Fesenko
The intracellular localization of human selenoprotein SelI and the degree of expression of its gene in different human tumor cell lines were determined. It was found that the SelI protein is present in the nucleus, cytoplasm, and endoplasmic reticulum and is absent in the nucleolus. Since the oxidative stress caused by a sharp increase in the content of free radicals in the body is one of the causes of malignant transformation, the study of the role of the trace element selenium and selenocysteine-containing proteins as antioxidants in carcinogenesis is of great scientific interest...
September 2017: Doklady. Biochemistry and Biophysics
Wei-Ju Lee, Yen-Ling Chen, Yi-Wen Chu, Du-Shieng Chien
BACKGROUND: Serum glutathione peroxidase-3 (GPx-3) is known as a key selenoprotein with antioxidant properties. GPx-3 deficiency has been associated with sepsis. The objectives of this study are (1) to compare the GPx-3 protein concentrations and GPx-3 bioactivity in normal healthy subjects and septic patients, and (2) to evaluate the relationship between GPx-3 bioactivity and its protein concentration. METHODS: Serum samples were collected from 50 normal healthy subjects and 70 septic patients...
October 31, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
George J Kahaly, Michaela Riedl, Jochem König, Tanja Diana, Lutz Schomburg
Context: Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Objective: Evaluate efficacy of add-on Se on medical treatment in GD. Design: Double-blind, placebo-controlled, randomized supplementation trial. Setting: Academic endocrine outpatient clinic. Patients: Seventy untreated hyperthyroid patients with GD. Intervention: Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
Mojgan Gharipour, Masoumeh Sadeghi, Mehrdad Behmanesh, Mansour Salehi, Pouya Nezafati, Amin Gharpour
  Selenium is a trace element required for a range of cellular functions. It is widely used for the biosynthesis of the unique amino acid selenocysteine [Sec], which is a structural element of selenoproteins. This systematic review focused on the possible relation between selenium and metabolic risk factors. The literature was searched via PubMed, Scopus, ISI Web of Science, and Google Scholar. Searches were not restricted by time or language. Relevant studies were selected in three phases. After an initial quality assessment, two reviewers extracted all the relevant data, whereas the third reviewer checked their extracted data...
October 23, 2017: Acta Bio-medica: Atenei Parmensis
Marco Mariotti, Sumangala Shetty, Lisa Baird, Sen Wu, Gary Loughran, Paul R Copeland, John F Atkins, Michael T Howard
Gene-specific expansion of the genetic code allows for UGA codons to specify the amino acid selenocysteine (Sec). A striking example of UGA redefinition occurs during translation of the mRNA coding for the selenium transport protein, selenoprotein P (SELENOP), which in vertebrates may contain up to 22 in-frame UGA codons. Sec incorporation at the first and downstream UGA codons occurs with variable efficiencies to control synthesis of full-length and truncated SELENOP isoforms. To address how the Selenop mRNA can direct dynamic codon redefinition in different regions of the same mRNA, we undertook a comprehensive search for phylogenetically conserved RNA structures and examined the function of these structures using cell-based assays, in vitro translation systems, and in vivo ribosome profiling of liver tissue from mice carrying genomic deletions of 3' UTR selenocysteine-insertion-sequences (SECIS1 and SECIS2)...
October 23, 2017: Nucleic Acids Research
Insun Song, Yong Jun Choi, Yilan Jin, Jung-Woo Kim, Jeong-Tae Koh, Hyung Min Ji, Seon-Yong Jeong, Ye-Yeon Won, Won Kim, Yoon-Sok Chung
To identify novel candidate genes associated with osteoporosis, RNA‑sequence analysis of human mesenchymal stem cells (hMSCs) from patients with osteoporosis (G3) and osteopenia (G2), and healthy controls (G1) was performed. Differentially expressed genes (DEGs) from among the three groups were identified. DEGs were separated into nine groups according to their gene expression patterns: UU (up and up), UF (up and flat), UD (up and down), FU (flat and up), FF (flat and flat), FD (flat and down), DU (down and up), DF (down and flat), and DD (down and down)...
October 2017: Molecular Medicine Reports
Nayoung Suh, Eun-Bi Lee
In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded in large scale before their administration. Prolonged culture in vitro results in cellular senescence-associated phenotypes, including accumulation of reactive oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell-related genes during in vitro expansion revealed that numerous canonical pathways were significantly changed. To determine the effect of selenocysteine (Sec), a rare amino acid found in several antioxidant enzymes, on the replicative senescence in hMSCs, we treated senescent hMSCs with Sec...
October 25, 2017: BMB Reports
Michael P Marciel, Peter R Hoffmann
Cancer survival is largely impacted by the dissemination of cancer cells from the original tumor site to secondary tissues or organs through metastasis. Targets for antimetastatic therapies have recently become a focus of research, but progress will require a better understanding of the molecular mechanisms driving metastasis. Selenoproteins play important roles in many of the cellular activities underlying metastasis including cell adhesion, matrix degradation and migration, invasion into the blood and extravasation into secondary tissues, and subsequent proliferation into metastatic tumors along with the angiogenesis required for growth...
2017: Advances in Cancer Research
Sarah P Short, Christopher S Williams
Selenium is a micronutrient essential to human health and has long been associated with cancer prevention. Functionally, these effects are thought to be mediated by a class of selenium-containing proteins known as selenoproteins. Indeed, many selenoproteins have antioxidant activity which can attenuate cancer development by minimizing oxidative insult and resultant DNA damage. However, oxidative stress is increasingly being recognized for its "double-edged sword" effect in tumorigenesis, whereby it can mediate both negative and positive effects on tumor growth depending on the cellular context...
2017: Advances in Cancer Research
Ewa Jabłońska, Edyta Reszka
Chemopreventive activity of selenium (Se) may influence epigenome. In this review, we have discussed two aspects of Se and epigenetics in cancer, related to (1) the association between Se and epigenetic regulation in cancer development and prevention; (2) epigenetic modification of selenoprotein-encoding genes in different cancers. In both issues, we focused on DNA methylation as the most investigated epigenetic mechanism. The existing evidence from experimental data in human cancer cell lines, rodents, and human studies in cancer-free subjects indicates that: high Se exposure leads to the inhibition of DNA methyltransferase expression/activity; the association between Se and global methylation remains unclear and requires further investigation with respect to the underlying mechanisms and possible nonlinear character of this relationship; Se affects methylation of specific tumor suppressor genes, possibly in a sex-dependent manner; and cancer phenotype is often characterized by altered methylation of selenoprotein-encoding genes, mainly glutathione peroxidase 3...
2017: Advances in Cancer Research
Camile C Fontelles, Thomas P Ong
Selenium (Se) is a micronutrient with promising breast cancer prevention and treatment potential. There is extensive preclinical evidence of Se mammary carcinogenesis inhibition. Evidence from epidemiological studies is, however, unclear and intervention studies are rare. Here, we examine Se chemoprotection, chemoprevention, and chemotherapy effects in breast cancer, focusing on associated cellular and molecular mechanisms. Se exerts its protective actions through multiple mechanisms that involve antioxidant activities, induction of apoptosis, and inhibition of DNA damage, cell proliferation, angiogenesis, and invasion...
2017: Advances in Cancer Research
Bastihalli T Diwakar, Arvind M Korwar, Robert F Paulson, K Sandeep Prabhu
Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis...
2017: Advances in Cancer Research
Elias S J Arnér
The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, encoded in human by TXNRD1) is implied to have several different roles in relation to cancer. Its physiologic functions may protect normal cells from carcinogenesis, but may also promote cancer progression if carcinogenesis nonetheless occurs. With distinct links to Nrf2 signaling, ribonucleotide reductase-dependent production of deoxyribonucleotides and its support of several antioxidant systems counteracting oxidative stress, the metabolic pathways regulated, and affected by TrxR1, are altogether of crucial importance in cancer...
2017: Advances in Cancer Research
Anna P Kipp
Five out of eight human glutathione peroxidases (GPxes) are selenoproteins and thus their expression depends on the selenium (Se) supply. Most Se-dependent GPxes are downregulated in tumor cells, while only GPx2 is considerably upregulated. Whether expression profiles of GPxes predict tumor development and patient survival is controversially discussed. Also, results from in vitro and in vivo studies modulating the expression of GPx isoforms provide evidence for both anti- and procarcinogenic mechanisms. GPxes are able to reduce hydroperoxides, which otherwise would damage DNA, possibly resulting in DNA mutations, modulate redox-sensitive signaling pathways affecting proliferation, differentiation, and cellular metabolism or initiate cell death...
2017: Advances in Cancer Research
Xianrong Xiong, Daoliang Lan, Jian Li, Yaqiu Lin, Mingyang Li
The objectives of the present study were to investigate the effects of selenium (Se) supplementation during in vitro maturation (IVM) on the developmental capacity of yak (Bos grunniens) oocytes. Nuclear maturation, DNA integrity, glutathione peroxidase (GSH-Px) activity, subsequent embryonic development, and gene expression after in vitro fertilization (IVF) were evaluated. The Se concentrations in yak plasma and follicular fluid were 0.142 and 0.069 μg/mL, respectively. The DNA damage in cumulus cells decreased significantly with 2 and 4 μg/mL supplementation of sodium selenite to IVM medium (P < 0...
October 16, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
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