The Role of Selenium in Health and Disease
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The Selenium Recycling Enzyme Selenocysteine Lyase: Regulation and Physiological Role in Glucose and Lipid Metabolism
THE SELENIUM RECYCLING ENZYME SELENOCYSTEINE LYASE: REGULATION AND PHYSIOLOGICAL ROLE IN GLUCOSE AND LIPID METABOLISM A DISSERTATION SUBMITTED TO THE GRADUATE DIVISION OF THE UNIVERSITY OF HAWAI‘I AT MĀNOA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN CELL AND MOLECULAR BIOLOGY MAY 2012 BY LUCIA ANDREIA SEALE Dissertation Committee: Marla J. Berry, Chairperson Robert A. Nichols Jun Pane‘e P. Reed Larsen E. Gordon Grau To my beloved parents Wilson & Madalena To my dear love André ii ACKNOWLEDGEMENTS A Ph.D. is a journey in a rough sea. As in all memorable expeditions, there is more to learn while traveling towards the final destination than at the destination itself. In several ways, it is the path and how you face the unexpected obstacles in this path that makes you a Doctor. The Ph.D. expedition does not allow an easy ride. While you travel through the waves and storms of your topic, figuring out a lot on and about yourself, you also encounter along the way people that make your stressful journey happier, nicer, safer, funnier and – why not – more challenging. They provided the emotional background that is not described in a scientific document. In my Ph.D. journey, these are the people about whom I’ll talk years ahead to friends, to whom I will silently smile when the nostalgic waves of the Ph.D. path break in the shores of my life. They are the unforgettable people that allowed me to arrive safe and sound in Doctorland. First and foremost, my greatest acknowledgement and gratitude goes to Dr. -
MPO) in Inflammatory Communication
antioxidants Review The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication Yulia Kargapolova * , Simon Geißen, Ruiyuan Zheng, Stephan Baldus, Holger Winkels * and Matti Adam Department III of Internal Medicine, Heart Center, Faculty of Medicine and University Hospital of Cologne, 50937 North Rhine-Westphalia, Germany; [email protected] (S.G.); [email protected] (R.Z.); [email protected] (S.B.); [email protected] (M.A.) * Correspondence: [email protected] (Y.K.); [email protected] (H.W.) Abstract: Myeloperoxidase is a signature enzyme of polymorphonuclear neutrophils in mice and humans. Being a component of circulating white blood cells, myeloperoxidase plays multiple roles in various organs and tissues and facilitates their crosstalk. Here, we describe the current knowledge on the tissue- and lineage-specific expression of myeloperoxidase, its well-studied enzymatic activity and incoherently understood non-enzymatic role in various cell types and tissues. Further, we elaborate on Myeloperoxidase (MPO) in the complex context of cardiovascular disease, innate and autoimmune response, development and progression of cancer and neurodegenerative diseases. Keywords: myeloperoxidase; oxidative burst; NETs; cellular internalization; immune response; cancer; neurodegeneration Citation: Kargapolova, Y.; Geißen, S.; Zheng, R.; Baldus, S.; Winkels, H.; Adam, M. The Enzymatic and Non-Enzymatic Function of 1. Introduction. MPO Conservation Across Species, Maturation in Myeloid Progenitors, Myeloperoxidase (MPO) in and its Role in Immune Responses Inflammatory Communication. Myeloperoxidase (MPO) is a lysosomal protein and part of the organism’s host-defense Antioxidants 2021, 10, 562. https:// system. MPOs’ pivotal function is considered to be its enzymatic activity in response to doi.org/10.3390/antiox10040562 invading pathogenic agents. -
Lncrna-MEG3 Functions As Ferroptotic Promoter to Mediate OGD Combined High Glucose-Induced Death of Rat Brain Microvascular Endothelial Cells Via the P53-GPX4 Axis
LncRNA-MEG3 functions as ferroptotic promoter to mediate OGD combined high glucose-induced death of rat brain microvascular endothelial cells via the p53-GPX4 axis Cheng Chen Xiangya Hospital Central South University Yan Huang Xiangya Hospital Central South University Pingping Xia Xiangya Hospital Central South University Fan Zhang Xiangya Hospital Central South University Longyan Li Xiangya Hospital Central South University E Wang Xiangya Hospital Central South University Qulian Guo Xiangya Hospital Central South University Zhi Ye ( [email protected] ) Xiangya Hospital Central South University https://orcid.org/0000-0002-7678-0926 Research article Keywords: lncRNA-MEG3, p53, ferroptosis, ischemia, GPX4, OGD, hyperglycemia, Posted Date: May 18th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-28622/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/21 Abstract Background Individuals with diabetes are exposed to a higher risk of perioperative stroke than non- diabetics mainly due to persistent hyperglycemia. lncRNA-MEG3 (long non-coding RNA maternally expressed gene 3) has been considered as an important mediator in regulating ischemic stroke. However, the functional and regulatory roles of lncRNA-MEG3 in diabetic brain ischemic injury remain unclear. Results In this study, RBMVECs (the rat brain microvascular endothelial cells) were exposed to 6 h of OGD (oxygen and glucose deprivation), and subsequent reperfusion via incubating cells with glucose of various high concentrations for 24 h to imitate in vitro diabetic brain ischemic injury. It was shown that the marker events of ferroptosis and increased lncRNA-MEG3 expression occurred after the injury induced by OGD combined with hyperglycemic treatment. -
Selenium Vs. Sulfur: Investigating the Substrate Specificity of a Selenocysteine Lyase
University of Central Florida STARS Electronic Theses and Dissertations, 2004-2019 2019 Selenium vs. Sulfur: Investigating the Substrate Specificity of a Selenocysteine Lyase Michael Johnstone University of Central Florida Part of the Biotechnology Commons Find similar works at: https://stars.library.ucf.edu/etd University of Central Florida Libraries http://library.ucf.edu This Masters Thesis (Open Access) is brought to you for free and open access by STARS. It has been accepted for inclusion in Electronic Theses and Dissertations, 2004-2019 by an authorized administrator of STARS. For more information, please contact [email protected]. STARS Citation Johnstone, Michael, "Selenium vs. Sulfur: Investigating the Substrate Specificity of a Selenocysteine Lyase" (2019). Electronic Theses and Dissertations, 2004-2019. 6511. https://stars.library.ucf.edu/etd/6511 SELENIUM VS. SULFUR: INVESTIGATING THE SUBSTRATE SPECIFICITY OF A SELENOCYSTEINE LYASE by MICHAEL ALAN JOHNSTONE B.S. University of Central Florida, 2017 A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the Burnett School of Biomedical Sciences in the College of Medicine at the University of Central Florida Orlando, Florida Summer Term 2019 Major Professor: William T. Self © 2019 Michael Alan Johnstone ii ABSTRACT Selenium is a vital micronutrient in many organisms. While traces are required for survival, excess amounts are toxic; thus, selenium can be regarded as a biological “double-edged sword”. Selenium is chemically similar to the essential element sulfur, but curiously, evolution has selected the former over the latter for a subset of oxidoreductases. Enzymes involved in sulfur metabolism are less discriminate in terms of preventing selenium incorporation; however, its specific incorporation into selenoproteins reveals a highly discriminate process that is not completely understood. -
Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals
antioxidants Review Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals Da-Young Lee, Moon-Young Song and Eun-Hee Kim * College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea; [email protected] (D.-Y.L.); [email protected] (M.-Y.S.) * Correspondence: [email protected]; Tel.: +82-31-881-7179 Abstract: Colorectal cancer still has a high incidence and mortality rate, according to a report from the American Cancer Society. Colorectal cancer has a high prevalence in patients with inflammatory bowel disease. Oxidative stress, including reactive oxygen species (ROS) and lipid peroxidation, has been known to cause inflammatory diseases and malignant disorders. In particular, the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-related protein 1 (KEAP1) pathway is well known to protect cells from oxidative stress and inflammation. Nrf2 was first found in the homolog of the hematopoietic transcription factor p45 NF-E2, and the transcription factor Nrf2 is a member of the Cap ‘N’ Collar family. KEAP1 is well known as a negative regulator that rapidly degrades Nrf2 through the proteasome system. A range of evidence has shown that consumption of phytochemicals has a preventive or inhibitory effect on cancer progression or proliferation, depending on the stage of colorectal cancer. Therefore, the discovery of phytochemicals regulating the Nrf2/KEAP1 axis and Citation: Lee, D.-Y.; Song, M.-Y.; verification of their efficacy have attracted scientific attention. In this review, we summarize the role Kim, E.-H. Role of Oxidative Stress of oxidative stress and the Nrf2/KEAP1 signaling pathway in colorectal cancer, and the possible and Nrf2/KEAP1 Signaling in utility of phytochemicals with respect to the regulation of the Nrf2/KEAP1 axis in colorectal cancer. -
Programmed Cell-Death by Ferroptosis: Antioxidants As Mitigators
International Journal of Molecular Sciences Review Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators Naroa Kajarabille 1 and Gladys O. Latunde-Dada 2,* 1 Nutrition and Obesity Group, Department of Nutrition and Food Sciences, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain; [email protected] 2 King’s College London, Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK * Correspondence: [email protected] Received: 9 September 2019; Accepted: 2 October 2019; Published: 8 October 2019 Abstract: Iron, the fourth most abundant element in the Earth’s crust, is vital in living organisms because of its diverse ligand-binding and electron-transfer properties. This ability of iron in the redox cycle as a ferrous ion enables it to react with H2O2, in the Fenton reaction, to produce a hydroxyl radical ( OH)—one of the reactive oxygen species (ROS) that cause deleterious oxidative damage • to DNA, proteins, and membrane lipids. Ferroptosis is a non-apoptotic regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is triggered when the endogenous antioxidant status of the cell is compromised, leading to lipid ROS accumulation that is toxic and damaging to the membrane structure. Consequently, oxidative stress and the antioxidant levels of the cells are important modulators of lipid peroxidation that induce this novel form of cell death. Remedies capable of averting iron-dependent lipid peroxidation, therefore, are lipophilic antioxidants, including vitamin E, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1) and possibly potent bioactive polyphenols. -
Purification and Characterization of a Novel Selenocysteine Lyase from Enterococcus Faecalis
University of Central Florida STARS Electronic Theses and Dissertations, 2004-2019 2014 Purification and Characterization of a Novel Selenocysteine Lyase from Enterococcus faecalis Samantha Nelson University of Central Florida Part of the Biotechnology Commons, and the Molecular Biology Commons Find similar works at: https://stars.library.ucf.edu/etd University of Central Florida Libraries http://library.ucf.edu This Masters Thesis (Open Access) is brought to you for free and open access by STARS. It has been accepted for inclusion in Electronic Theses and Dissertations, 2004-2019 by an authorized administrator of STARS. For more information, please contact [email protected]. STARS Citation Nelson, Samantha, "Purification and Characterization of a Novel Selenocysteine Lyase from Enterococcus faecalis" (2014). Electronic Theses and Dissertations, 2004-2019. 4807. https://stars.library.ucf.edu/etd/4807 PURIFICATION AND CHARACTERIZATION OF A NOVEL SELENOCYSTEINE LYASE FROM ENTEROCOCCUS FAECALIS by SAMANTHA NELSON B.S. University of Central Florida, 2012 A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in the Burnett School of Biomedical Sciences in the College of Medicine at the University of Central Florida Orlando, Florida Summer Term 2014 Major Professor: William T. Self © 2014 Samantha Nelson ii ABSTRACT A previous study identified Enterococcus faecalis as one of two bacteria known to have the selD gene and other selenium related genes without having the genes necessary to make selenocysteine or selenouridine. EF2570, a gene in the cluster, was later shown to be upregulated during biofilm formation and also responsible for a selenite- and molybdate-dependent increase in biofilm formation in vitro. -
Myeloperoxidase-Mediated Platelet Release Reaction
Myeloperoxidase-Mediated Platelet Release Reaction Robert A. Clark J Clin Invest. 1979;63(2):177-183. https://doi.org/10.1172/JCI109287. Research Article The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both lytic and nonlytic effects on platelets were assessed by comparison of the simultaneously measured release of a dense-granule marker, [3H]serotonin, and a cytoplasmic marker, [14C]adenine. Incubation of platelets with H2O2 alone (20 μM H2O2 for 10 min) resulted in a small, although significant, release of both serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H2O2 concentrations (>0.1 mM) or prolonged incubation (1-2 h). Serotonin release by H2O2 was markedly enhanced by the addition of myeloperoxidase and a halide. Under these conditions, there was a predominance of release of serotonin (50%) vs. adenine (13%), suggesting, in part, a nonlytic mechanism. Serotonin release by the complete peroxidase system was rapid, reaching maximal levels in 2-5 min, and was active at H2O2 concentrations as low as 10 μM. It was blocked by agents which inhibit peroxidase (azide, cyanide), 2+ degrade H2O2 (catalase), chelate Mg (EDTA, but not EGTA), or inhibit platelet metabolic activity (dinitrophenol, deoxyglucose). These results suggest that the myeloperoxidase system initiates the release of platelet constituents primarily by a nonlytic process analogous to the platelet release reaction. Because components of the peroxidase system (myeloperoxidase, H2O2) are secreted by activated neutrophils, the reactions described here […] Find the latest version: https://jci.me/109287/pdf Myeloperoxidase-Mediated Platelet Release Reaction ROBERT A. -
GRAS Notice 665, Lactoperoxidase System
GRAS Notice (GRN) No. 665 http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm ORIGINAL SUBMISSION 000001 Mo•·gan Lewis Gf<N Ob()&h5 [R1~~~~~~[Q) Gary L. Yingling Senior Counsel JUL 1 8 2016 + 1.202. 739 .5610 gary.yingling@morganlewis .com OFFICE OF FOO~ ADDITIVE SAFETY July 15, 2016 VIA FEDERAL EXPRESS Dr. Antonia Mattia Director Division of Biotechnology and GRAS Notice Review Office of Food Additive Safety (HFS-200) Center for Food Safety and Applied Nutrition Food and Drug Administration 5100 Paint Branch Parkway College Park, MD 20740-3835 Re: GRAS Notification for the Lactoperoxidase System Dear Dr. Mattia: On behalf of Taradon Laboratory C'Taradon"), we are submitting under cover of this letter three paper copies and one eCopy of DSM's generally recognized as safe ("GRAS'') notification for its lactoperoxidase system (''LPS''). The electronic copy is provided on a virus-free CD, and is an exact copy of the paper submission. Taradon has determined through scientific procedures that its lactoperoxidase system preparation is GRAS for use as a microbial control adjunct to standard dairy processing procedures such as maintaining appropriate temperatures, pasteurization, or other antimicrobial treatments to extend the shelf life of the products. In many parts of the world, the LPS has been used to protect dairy products, particularly in remote areas where farmers are not in close proximity to the market. In the US, the LPS is intended to be used as a processing aid to extend the shelf life of avariety of dairy products, specifically fresh cheese including mozzarella and cottage cheeses, frozen dairy desserts, fermented milk, flavored milk drinks, and yogurt. -
Kinetics of Interconversion of Redox Intermediates of Lactoperoxidase
Jpn. J. Infect. Dis., 57, 2004 Kinetics of Interconversion of Redox Intermediates of Lactoperoxidase, Eosinophil Peroxidase and Myeloperoxidase Paul Georg Furtmüller, Walter Jantschko, Martina Zederbauer, Christa Jakopitsch, Jürgen Arnhold1 and Christian Obinger* Metalloprotein Research Group, Division of Biochemistry, Department of Chemistry, BOKU-University of Natural Resources and Applied Life Sciences, 1Institute of Medical Physics and Biophysics, School of Medicine, University of Leipzig, Leipzig, Germany SUMMARY: Myeloperoxidase, eosinophil peroxidase and lactoperoxidase are heme-containing oxidoreductases, which undergo a series of redox reactions. Though sharing functional and structural homology, reflecting their phylogenetic origin, differences are observed regarding their spectral features, substrate specificities, redox properties and kinetics of interconversion of the relevant redox intermediates ferric and ferrous peroxidase, compound I, compound II and compound III. Depending on substrate availability, these heme enzymes path through the halogenation cycle and/or the peroxidase cycle and/or act as poor (pseudo-) catalases. Today - based on sequence homologies, tertiary structure and the halide ions is the following: I– > Br– > Cl–. All peroxidases can nature of the heme group - two heme peroxidase superfamilies are oxidize iodide. At neutral pH, only MPO is capable to oxidize distinguished, namely the superfamily containing enzymes from chloride at a reasonable rate (4), and it is assumed that chloride and archaea, bacteria, fungi and plants (1) and the superfamily of thiocyanate are competing substrates in vivo. EPO can oxidize mammalian enzymes (2), which contains myeloperoxidase (MPO), chloride only at acidic pH (5), and at normal plasma concentrations, eosinophil peroxidase (EPO), lactoperoxidase (LPO) and thyroid bromide and thiocyanate function as substrates, whereas for LPO peroxidase (TPO). -
Parental Selenium Nutrition Affects the One-Carbon Metabolism
life Article Parental Selenium Nutrition Affects the One-Carbon Metabolism and the Hepatic DNA Methylation Pattern of Rainbow Trout (Oncorhynchus mykiss) in the Progeny 1, 2, 1 1 Pauline Wischhusen y , Takaya Saito y ,Cécile Heraud , Sadasivam J. Kaushik , 1 2 1, , Benoit Fauconneau , Philip Antony Jesu Prabhu , Stéphanie Fontagné-Dicharry * y 2, and Kaja H. Skjærven y 1 INRAE, University of Pau and Pays de l’Adour, E2S UPPA, NUMEA, 64310 Saint Pee sur Nivelle, France; [email protected] (P.W.); [email protected] (C.H.); [email protected] (S.J.K.); [email protected] (B.F.) 2 Institute of Marine Research, P.O. Box 1870, 5020 Bergen, Norway; [email protected] (T.S.); [email protected] (P.A.J.P.); [email protected] (K.H.S.) * Correspondence: [email protected] These authors contributed equally to this work. y Received: 11 June 2020; Accepted: 23 July 2020; Published: 25 July 2020 Abstract: Selenium is an essential micronutrient and its metabolism is closely linked to the methionine cycle and transsulfuration pathway. The present study evaluated the effect of two different selenium supplements in the diet of rainbow trout (Onchorhynchus mykiss) broodstock on the one-carbon metabolism and the hepatic DNA methylation pattern in the progeny. Offspring of three parental groups of rainbow trout, fed either a control diet (NC, basal Se level: 0.3 mg/kg) or a diet supplemented with sodium selenite (SS, 0.8 mg Se/kg) or hydroxy-selenomethionine (SO, 0.7 mg Se/kg), were collected at swim-up fry stage. -
Positive Granules in Normal Circulating Neutrophils: an Ultrastructural Study by Cryosection
Histol Histopathol (1998) 13: 405-414 Histology and 001: 10.14670/HH-13.405 Histopathology http://www.hh.um.es From Cell Biology to Tissue Engineering Morphological heterogeneity of myeloperoxidase positive granules in normal circulating neutrophils: an ultrastructural study by cryosection N. Saitol, F. Satol, M. Asakal, N. Takemori2 and Y. Kohgo3 1Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Hokkaido, 2Asahikawa Kohosei General Hospital, Asahikawa, Hokkaido, and 3Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan Summary. Ultrastructural localization of myelo and shape (Ackerman and Clark, 1971). In general, the peroxidase (MPO) in the granules of human circulating ultrastructural localization of MPO has been performed neutrophils was examined by cryosection. On careful employing a cytochemical technique (Graham and comparison with the morphological characteristics of the Karnovksy, 1966). However, using this technique, the granules by conventional transmission electron homogeneous chemical product induced by the microscopic study, large MPO-positive granules were cytochemical reaction makes it difficult to identify divided into five types by immunocryoultramicrotomy intragranular structure. Moreover, it is not easy to using monoclonal antibody. Double staining of MPO and precisely pinpoint which granules observed by lactoferrin (or lysozyme) was also performed. Lacto conventional transmission electron microscopy are MPO ferrin was generally detected in MPO-negative granules. positive (MPO+). To overcome these disadvantages, an Lysozyme immunostaining was present in MPO-positive ultrastructural immunogold staining, by which the and -negative granules. These data may suggest different structure can still be observed even after positive functions among large MPO-positive granules of human reaction for detecting intragranular proteins, has been circulating neutrophils.