Selenium

Dolph L. Hatfi eld • Ulrich Schweizer Petra A. Tsuji • Vadim N. Gladyshev Editors

Selenium Its Molecular Biology and Role in Human Health

Fourth Edition

ISBN 978-3-319-41281-8 ISBN 978-3-319-41283-2 (eBook) DOI 10.1007/978-3-319-41283-2

Library of Congress Control Number: 2016948304

© Springer Science+Business Media, LLC 2001, 2006, 2012, 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made.

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Editors Dolph L. Hatfi eld Mouse Cancer Genetics ProgramNational Cancer Institute National Institutes of Health Bethesda , MD , USA

Petra A. Tsuji Department of Biological Sciences Towson University Towson , MD , USA

Ulrich Schweizer Institut für Biochemie und

Molekularbiologie Rheinische Friedrich-Wilhelms-Universität

Bonn Bonn , Nordrhein-Westfalen , Germany

Vadim N. Gladyshev Division of GeneticsDepartment of MedicineBrigham and Women’s Hospital Harvard Medical School Boston, MA , USA

v

Dedication

This book is dedicated to the pioneers in the selenium fi eld, who provided the foundation for the enormous amount of research that has occurred in recent years, bringing extraordinary insights to selenium biology and its role in health and development of humans and other mammals. The discoverer of selenium, Jöns Jacob Berzelius, a Swedish chemist, deserves special recognition as he identifi ed this element in 1817 as a by- product of sulfuric acid production. As we are now on the verge of the 200th anniversary of the Berzelius discovery, this new edition is particularly timely. The anniversary will also be the prevailing theme of The 11th International Symposium on Selenium in Biology and Medicine and The 5th International Conference on Selenium in the Environment and Human Health , to be held in Stockholm, Sweden, in August 2017.

One of the early studies that impacted how selenium was viewed in mammalian health was carried out by Kurt Franke. He reported in 1934 that diseases found primarily in livestock and military horses, called alkali disease and blind staggers disease, were caused by these animals ingesting selenium- accumulating plants. These seleniferous plants grow in the Midwest United States in areas where the soil is rich in selenium and the livestock and military horses had grazed [1]. This was an important fi nding as it demonstrated that high levels of selenium were toxic to animals. An early study that began to change how selenium was viewed in mammalian health occurred 20 years later than the Franke endeavor, when Jane Pinsent showed that selenium is required for formate dehydrogenase synthesis in Escherichia coli [2].

Klaus Schwarz and Calvin Foltz subsequently changed the image of selenium forever in 1957, when they demonstrated that selenium protected rats against liver necrosis [3]; and selenium was soon recognized as an essential trace element in mammals. The impact that Schwarz’s and Foltz’s discovery had on the livestock industry followed shortly after their report and was monumental in that many disorders described in farm animals were recognized as being related to selenium defi ciency, such as exudative diathesis and pancreatic degeneration in poultry,

vi

hepatosis dietetica in swine, and white muscle disease in lambs and calves (reviewed in [4]). In fact, supplementing the diets of livestock globally with selenium was reported in 1986 to have saved the livestock industry in the hundreds of millions of dollars [5], which would equate to multi-billions of dollars by today’s fi nancial standards. The pioneer work of J.E. Oldfi eld on white muscle disease in lambs in 1957 provided much of the foundation for the impact of selenium on the livestock industry (described in [4]; and see footnote in [4] regarding James Oldfi eld’s recent death).

Another discovery that occurred early in the developing selenium fi eld was the identifi cation in 1973 of selenium as a covalently bound component of glutathione peroxidase 1 by Leopold Flohé [6] and J.T. Rotruck [7]. The same year, Thressa Stadtman found selenium in Protein A of glycine reductase [8], and Jan Andreesen showed that the reason why formate dehydrogenase synthesis required selenium was that the protein itself incorporated the element [9]. Subsequently, in 1976, Thressa Stadtman showed that the selenium-containing component of selenoproteins was selenocysteine (Sec) [10]. In addition, Chambers et al. [11] and Zinoni et al. [12] demonstrated in 1986 that TGA in the genes of mouse glutathione peroxidase 1 and bacterial formate dehydrogenase, respectively, coincided with the selenocysteine residue in the resulting gene products. These latter studies provided the initial evidence that the genetic code contained 21 amino acids, and the code would need to be expanded. The further elegant work on the genetics of selenocysteine biosynthesis and selenocysteine incorporation into protein in bacteria, primarily by August Böck [13], laid the conceptual framework and was instrumental for later delineating these processes in archaea and eukaryotes. We refer the interested reader to a comprehensive review which encompasses far more details on the early years of selenium research [14].

These and the many other highly signifi cant discoveries from 1817 through the twentieth century have provided the foundation for recognition of how selenium may act at the molecular level. The signifi cant and intricate impact of selenium in many biological processes clearly identifi es research on selenium and selenocysteine, the 21st proteinogenic amino acid, as highly important. As the 200th anniversary of the discovery of selenium approaches, we gratefully dedicate this book to the pioneers of selenium research.

References

1. KW Franke 1934 J Nutr 8:597 2. J Pinsent 1954 Biochem J 57:10 3. K Schwarz, CM Foltz 1957 J Am Chem Soc 79:3292 4. JE Oldfi eld 2002 J Animal Sci Online Supplement 11:1 1

1 We sadly note that our colleague, dear friend and a true pioneer in the selenium fi eld, James E. Oldfi eld, died on April 3, 2016.

Dedication

vii

5. GF Combs, Jr., SB Combs 1986 The Role of Selenium in Nutrition , (Academic Press, New York)

6. L Flohé et al. 1973 FEBS Lett 32:132 7. JT Rotruck et al. 1973 Science 179:588 8. DC Turner, TC Stadtman 1973 Arch Biochem Biophys 154:366 9. JR Andreesen, LG Ljungdahl 1973 J Bacteriol 116:867 10. JE Cone et al. 1976 Proc Natl Acad Sci U S A 73:2659 11. I Chambers et al. 1986 EMBO J 5:1221 12. F Zinoni et al. 1986 Proc Natl Acad Sci 83:4650 13. S Yoshizawa, A Böck 2009 Biochim Biophys Acta 1790:1404 14. L Flohé L 2009 Biochim Biophys Acta 1790:1389

Dolph L. Hatfi eld, Ulrich Schweizer, Petra A. Tsuji and Vadim N. Gladyshev, Editors Elias S.J. Arnér, Organizer of Se2017 , The 11th International Symposium on Selenium in Biology

and Medicine and 5th International Conference on Selenium in the Environment and Human Health , Stockholm, Sweden, August 13–17, 2017

Dedication

ix

Foreword

Selenium is a basic element found in the same chalcogen group of the periodic system as oxygen, sulfur, and tellurium. “ What is more, it is in this regard, midway between sulfur and tellurium, and has almost more characters of sulfur than of tel-lurium ,” as its discoverer Jöns Jacob Berzelius cleverly concluded after his very fi rst experiences, in the year 1817, with this element [1] (the author’s translation from Swedish). That was indeed an impressively correct description of the chemical character of selenium. Today, as we approach the 200th anniversary of Berzelius’ discovery of selenium, knowledge about its functions in biology is extensive. Research for the last couple of decades has revealed how selenium is intricately linked to a wide variety of important reactions in redox biochemistry, with seleno-proteins employing the unique chemistry of selenium in the form of selenocysteine, which in turn is co-translationally inserted by highly complex synthesis mecha-nisms that, in fact, redefi ne the genetic code. We also know that low molecular weight selenium compounds and metabolites can, just as selenoproteins, have either health-promoting or toxic effects to cells and organisms, with the fi nal outcome depending upon the entity of compounds, their concentrations, and the context of exposure. Conversely, defi ciency of selenium can also give rise to disease in humans and other mammals, since in most organisms that express selenoproteins, at least one selenoprotein is likely to be essential. However, it is not fully understood how many other organisms, such as plants and many classes of microorganisms, can survive without selenoproteins and, conversely, why many of those organisms that have selenoproteins seem to depend upon them. Indeed, many questions have remained unanswered and there are many aspects in selenium biology, and in the molecular interactions between selenium, sulfur, and oxygen, that are as thought provoking as they must have been in the very early days of Berzelius.

In this fourth edition of the book Selenium: Its Molecular Biology and Role in Human Health , edited by four very well-known scientists in selenoprotein research, Dolph Hatfi eld, Ulrich Schweizer, Petra Tsuji, and Vadim Gladyshev, 50 chapters introduce and discuss the very rapid development in recent years of research on selenium and selenoproteins. These chapters are organized in fi ve thematic parts. In the fi rst part, the intricate molecular details of selenoprotein synthesis are introduced

x

and outstanding questions posted. What were the evolutionary mechanisms that led to an alternative usage of the stop codon UGA as a sense codon for selenocysteine, utilizing secondary structures in the mRNA as the decoding signal? What molecular mechanisms yield specifi city and effi ciency in this decoding process, and exactly how specifi c or effi cient is selenoprotein synthesis? What are the common denomi-nators in selenoprotein synthesis among different classes or kingdoms of life and what are the differences? How is selenocysteine itself synthesized and degraded, and how is the metabolism of selenium-containing compounds, which is highly complex, integrated into a biological context? What are the absolute chemical dif-ferences between selenocysteine and cysteine and what biological signifi cance do such differences play? These types of fundamental questions are still mainly unan-swered, but knowledge about these topics has nonetheless increased very rapidly in recent years, which is illustrated and covered by the ten chapters in Part I.

Part II of this book focuses on biological roles of selenoproteins with confi rmed activities, and also some with yet only proposed or unknown functions. What sele-noproteins are expressed in different organisms, how are their expression patterns regulated, and what are their functions, in the forms of either isolated proteins or in a biological context? Can a better understanding of the function of individual sele-noproteins contribute to knowledge of the pathogenesis of diseases? If so, can such knowledge form the basis for novel therapy, employing specifi c targeting of indi-vidual selenoproteins? Some selenoproteins have been more studied than others, but for all selenoproteins, there are still many questions left unanswered and the 14 chapters in Part II focus on these topics and the recent developments in this fi eld.

Many epidemiological studies have revealed that selenium intake indeed has a direct effect on human health and disease, but a full, or perhaps even only a partial and superfi cial, understanding of the casual links in this relation is still missing. As an overly high selenium intake may give rise to toxic effects, while defi ciency also leads to disease, it is intriguing that the nutritional intake span for selenium is so narrow that even small variations in food contents of selenium and its long-term intake may possibly be linked to disease. In Part III of this book, 11 chapters discuss these fascinating aspects of selenium intake in relation to human health.

Although biological effects of selenium may be derived from actions of both low molecular weight metabolites and selenoproteins, it is clear that selenoproteins carry out many important functions in humans that may be important in maintaining fi t-ness and health. Thus, several of the epidemiologically observed links between sele-nium intake levels and disease that are discussed in Part III are likely to be linked to effects on selenoprotein function; and perhaps more so in the case of selenium defi -ciency that may lead to insuffi cient expression and function of one or several sele-noproteins. Importantly, like for proteins in general, selenoprotein function is tightly linked to control of expression and that, in turn, will be affected not only by sele-nium availability but also by the integrity of selenoprotein-encoding genes and their transcription and translation machineries. As these genes and factors may be affected by mutations and other gene alterations, selenoprotein function can also be modu-lated by genetic aberrations. In Part IV, these aspects of selenium and selenoprotein function are further discussed in ten chapters, focusing upon the modulation of the expression patterns and functions of specifi c selenoproteins in relation to disease.

Foreword

xi

In the fi nal Part V, fi ve chapters discuss different animal models for studies of selenium and selenoprotein function. These models include deliberate genetic tar-geting of specifi c selenoproteins, or factors required for selenoprotein synthesis, in mice as well as unique selenium usage or the effects of selenium, in particular, in other animals, such as the naked mole rat or in livestock. By observations and con-clusions from these animal models, important insights into selenium functions in biology at large are clearly gained.

As is powerfully illustrated by the 50 up-to-date chapters in this book, selenium research has made fantastic progress since the initial discovery of selenium by Berzelius, with an almost exponential growth in knowledge in recent years. Today, more than 30,000 articles can be found in PubMed when searching for “selenium or selenocysteine or selenoprotein.” Nonetheless, it is painfully obvious how much is still unknown in this research fi eld, with crucial questions clearly remaining to be answered. How can so many classes of organisms live without any selenoprotein, when selenoproteins seem to be essential for life in mammals? What are the func-tions and biological roles for all those selenoproteins in nature that have thus far only been observed, but not yet studied at any depth? What exact mechanisms can be determined to explain the links between selenium status and disease? How can any causal links between aberrations in selenium biology and disease be exploited for novel and effi cient therapy? The chapters in this book provide a most solid foun-dation as a starting point for the continued research on these questions and topics. As we are now approaching the 200th anniversary of Berzelius’ discovery of sele-nium, the largest-ever international selenium conference is organized in Stockholm on August 13–17, 2017 (see www.Se2017.se ), where a majority of the scientists in selenium research are expected to meet. Also at that conference, this book serves to provide a solid foundation for discussions and presentations, with its comprehen-sive up-to-date coverage of the molecular biology of selenium and the links of this element to human and animal health. With selenium research being more vibrant than ever, we can look forward to an exciting development of this topic, and we hope that the results of all ongoing selenium studies may lead to better measures for improved human health. To facilitate such a goal, it is recommended that the scien-tists active and interested in selenium research read this book, which will help to give all parties a common platform of informed knowledge in the fi eld. The editors of this book are cordially thanked for taking the signifi cant efforts of compiling and editing its many chapters, and every scientist in the selenium research area is thank-fully acknowledged for the continuous efforts to further expand the boundaries in selenium knowledge.

Stockholm, Sweden Elias S. J. Arnér

Reference

1. JJ Berzelius 1818 “Undersökning af en ny Mineral-kropp, funnen i de orenare sorterna af det i Falun tillverkade svafl et” Afhandlingar i fysik, kemi och mineralogi 6:42

Foreword

xiii

Pref ace

The fi rst edition of Selenium: Its Molecular Biology and Role in Human Health was published in 2001 and largely covered the research in the selenium fi eld for the preceding 30 years with special emphasis on “new and surprising insights into bio-chemical, molecular and genetic aspects of this fascinating element.” The book con-tained 25 chapters with 46 contributors. The selenium fi eld expanded in the ensuing years, which was refl ected in the second edition, published in 2006, containing 35 chapters with 71 contributors, and the third edition, published in 2012, which con-tained 45 chapters with 96 contributors. Marla Berry played a major role in the success of the second and third editions, which she coedited. In the present edition, Ulrich Schweizer and Petra (Peko) Tsuji are serving as coeditors.

The fourth edition of Selenium: Its Molecular Biology and Role in Human Health , like the previous ones, refl ects the patterns of growth and diversity in the selenium fi eld. The current edition contains 50 chapters and has 119 contributors. Some of the principal areas in the selenium fi eld, which fl ourished the most during the last 5 years, are the continued in-depth analyses of functions and regulation of selenoproteins, primarily in human health and disease, and in particular, cancer. While many publications emphasize selenium as having chemopreventive activity, it has become apparent in the last few years that this element also has a role in pro-moting cancer, and this pattern most likely applies to other chronic disorders. In retrospect, selenium’s role in driving malignancies is not surprising, since unhealthy cells, and specifi cally cancer cells, require potent, robust systems that maintain their redox homeostasis and support rapid growth. Selenoproteins manifesting a “Dr. Jekyll and Mr. Hyde personality” in both preventing and promoting cancer, and the interplay of different oxidoreductase systems, are discussed in various chapters.

Interestingly, glutathione peroxidase 4 has recently been shown to have roles in cancer progression and ferroptosis, a form of non-apoptotic cell death, whereas research on thioredoxin reductase has highlighted the ever increasing roles of this important selenoenzyme in redox biology. It is also becoming clear that selenium- dependent deiodinases not only contribute to circulating thyroid hormone homeo-stasis, but their local regulation bestows on them key roles in organ development and stem cell biology, and thus affects wound healing and cancer progression.

xiv

Modern genetics has also played a major role in selenium research. Mouse models were instrumental in identifying physiological functions of selenoproteins. Currently, all but six selenoproteins have been individually inactivated in mice and interesting phenotypes have been discovered in many of the mice lacking a specifi c selenoprotein- encoding gene. In parallel, several inherited diseases affecting sele-noproteins or their biosynthesis have been identifi ed in humans, and the severity of the symptoms highlights the roles that selenoproteins play in human health. Many polymorphic forms detected in the genes of several selenoproteins have been reported to have different consequences on the corresponding selenoprotein func-tion, including a strong association with disease.

Some important areas in the selenium fi eld have largely been solved and/or have progressed slowly, but they have previously provided a wealth of information. A number of these areas, therefore, have also been included in the book to serve as a source for those readers not working specifi cally in the selenium fi eld. In addition, inclusion of these fi ndings makes this edition as complete as possible in represent-ing most aspects of the selenium biology fi eld.

Due to the discovery of all selenoprotein genes in mammals and elucidation of the roles of the resulting selenoproteins in cellular metabolism, health, and develop-ment, much of the selenium fi eld has focused on selenoproteins in the last 15 years as refl ected in the present and previous editions. Thus, the debate that existed in the selenium fi eld at the beginning of this century, i.e., whether small molecular weight selenocompounds or selenoproteins were largely responsible for the many health benefi ts attributed to selenium, shifted the pendulum largely to the side of seleno-proteins as the responsible benefactors. However, we anticipate that small molecu-lar weight selenocompounds will, once again, come much more into focus refl ecting selenium toxicity.

The current edition, which covers so many aspects of the selenium fi eld by dif-ferent investigators, naturally has insights and opinions that occasionally are at vari-ance with each other. We consider these dissimilarities an asset to the reader as they illustrate how different investigators approach these issues and provide a better overall view of current research in the selenium fi eld.

We were informed by Springer that the third edition of this book was in the top 25 % of all e-books published in 2014 with regard to copies acquired, views, and downloads. We hope the new edition with its further expanded scope will be as well received by the readers. It is an exciting time to be in the selenium fi eld and contribute to it; and we look forward to what the future brings with regard to new discoveries involving this element, selenoproteins, and their roles in health and development.

Bethesda, MD, USA Dolph L. Hatfi eld Bonn, Germany Ulrich Schweizer Towson, MD, USA Petra A. Tsuji Boston, MA, USA Vadim N. Gladyshev

Preface

xv

Acknowledgements

We gratefully acknowledge Bradley A. Carlson, who organized virtually every detail of this book. The fi nal assembly of the book was also Bradley’s undertaking. These were monumental tasks, and simply said, the fourth edition of Selenium: Its Molecular Biology and Role in Human Health would not have been published with-out his contributions.

We also acknowledge our spouses Mary J. Wilson (DLH), Stefanie Schweizer (US), Lee Barnhill (PAT), and Helen Gladysheva (VNG) for their patience and sup-port in the many hours taken away from them in our preparing the fourth edition of this book.

xvii

Part I The Machinery of Selenoprotein Biosynthesis

1 Selenocysteine tRNA[Ser]Sec: From Nonsense Suppressor tRNA to the Quintessential Constituent in Selenoprotein Biosynthesis ................................................................. 3 Bradley A. Carlson , Byeong Jae Lee , Petra A. Tsuji , Ryuta Tobe , Jin Mo Park , Ulrich Schweizer , Vadim N. Gladyshev , and Dolph L. Hatfi eld

2 Eukaryotic Mechanisms of Selenocysteine Incorporation and Its Reconstitution In Vitro .............................................................. 13 Mark H. Pinkerton and Paul R. Copeland

3 Probing Selenoprotein Translation by Ribosome Profi ling ................. 25 Michael T. Howard

4 Pathways in De Novo Biosynthesis of Selenocysteine and Cysteine in Eukaryotes .................................................................... 39 Vadim N. Gladyshev , Bradley A. Carlson , and Dolph L. Hatfi eld

5 Prokaryotic Selenoprotein Biosynthesis and Function ........................ 47 Michael Rother

6 The Role of Selenium in Human Evolution .......................................... 59 Louise White and Sergi Castellano

7 The Chemistry of Selenocysteine in Proteins ....................................... 73 Rebecca N. Dardashti , Linoy Dery , Reem Mousa , Shahar Dery , Post S. Reddy , and Norman Metanis

8 Evolution of Selenophosphate Synthetase ............................................ 85 Marco Mariotti , Didac Santesmasses , and Roderic Guigó

9 Structure and Mechanism of Selenocysteine Synthases ...................... 101 Malgorzata Dobosz-Bartoszek and Miljan Simonović

Contents

xviii

10 Mechanism, Structure, and Biological Role of Selenocysteine Lyase ........................................................................... 113 Hisaaki Mihara , Ryuta Tobe , and Nobuyoshi Esaki

Part II Selenoproteins, Their Occurrence and Function

11 Eukaryotic Selenoproteomes .................................................................. 127 Vadim N. Gladyshev

12 Prokaryotic Selenoproteins and Selenoproteomes ............................... 141 Yan Zhang

13 Functional Genomics of Selenoproteins and Se-responsive Pathways .................................................................................................. 151 Catherine Méplan and John Hesketh

14 Selenium Regulation of the Selenoprotein and Non-selenoprotein Transcriptomes in a Variety of Species ......... 175 Roger A. Sunde

15 77Se NMR Spectroscopy of Selenoproteins ............................................ 187 Jun Liu and Sharon Rozovsky

16 Thioredoxin Reductase 1 as an Anticancer Drug Target .................... 199 Edward E. Schmidt and Elias S. J. Arnér

17 Basics and News on Glutathione Peroxidases ....................................... 211 Leopold Flohé and Regina Brigelius-Flohé

18 Glutathione Peroxidase 4 ........................................................................ 223 Matilde Maiorino , Valentina Bosello-Travain , Giorgio Cozza , Giovanni Miotto , Laura Orian , Antonella Roveri , Stefano Toppo , Mattia Zaccarin , and Fulvio Ursini

19 The 15 kDa Selenoprotein: Insights into Its Regulation and Function ............................................................................................ 235 Bradley A. Carlson , Janelle M. Hartman , and Petra A. Tsuji

20 Selenoprotein K and Protein Palmitoylation in Regulating Immune Cell Functions .......................................................................... 245 Peter R. Hoffmann

21 Selenoprotein M: Structure, Expression and Functional Relevance ...................................................................... 253 Ting Gong , Marla J. Berry , and Matthew W. Pitts

22 Selenoprotein P and Selenium Distribution in Mammals ................... 261 Ulrich Schweizer , Lutz Schomburg , and Josef Köhrle

Contents

xix

23 Selenoprotein T: From Discovery to Functional Studies Using Conditional Knockout Mice ........................................................ 275 Loubna Boukhzar , Yannick Tanguy , Houssni Abid , Matthieu Castex , Abdallah Hamieh , Ifat Alsharif , Dorthe Cartier , Gaëtan Prevost , Anthony Falluel-Morel , Isabelle Lihrmann , Abdeslam Chagraoui , and Youssef Anouar

24 Biochemistry and Function of Methionine Sulfoxide Reductase ........ 287 Byung Cheon Lee

Part III Dietary Selenium and Its Impact on Human Health

25 Selenium: Dietary Sources, Human Nutritional Requirements and Intake Across Populations .............................................................. 295 Kristin M. Peters , Sarah E. Galinn , and Petra A. Tsuji

26 Human Clinical Trials Involving Selenium ........................................... 307 Lutz Schomburg

27 Status of Dietary Selenium in Cancer Prevention ................................ 321 Gerald F. Combs Jr. and Lin Yan

28 Selenium in HIV/AIDS ........................................................................... 333 Adriana Campa , Sabrina Sales Martinez , and Marianna K. Baum

29 Genetic Variations in the Genes for Selenoproteins Implicate the Encoded Proteins in Cancer Etiology ............................................. 343 Rama Saad and Alan M. Diamond

30 Is Adequate Selenium Important for Healthy Human Pregnancy? ................................................................................ 353 Margaret P. Rayman

31 The Epidemiology of Selenium and Human Health ............................ 365 Marco Vinceti , Barbara Burlingame , Tommaso Filippini , Androniki Naska , Annalisa Bargellini , and Paola Borella

32 Sex-Specifi c Differences in Biological Effects and Metabolism of Selenium .................................................................. 377 Lutz Schomburg

33 Selenium and Endocrine Tissues ........................................................... 389 Josef Köhrle

34 Selenium Antagonism with Mercury and Arsenic: From Chemistry to Population Health and Demography ................... 401 Anatoly V. Skalny , Margarita G. Skalnaya , Alexandr A. Nikonorov , and Alexey A. Tinkov

35 Biological Selenium Species and Selenium Speciation in Biological Samples .............................................................................. 413 Katarzyna Bierla , Joanna Szpunar , and Ryszard Lobinski

Contents

xx

Part IV Selenoproteins in Human Health

36 Selenoproteins in Nervous System Development, Function and Degeneration .................................................................... 427 Ulrich Schweizer

37 Interplay of Selenoproteins and Different Antioxidant Systems in Various Cancers ................................................................... 441 Petra A. Tsuji , Bradley A. Carlson , Byeong J. Lee , Vadim N. Gladyshev , and Dolph L. Hatfi eld

38 Glutathione Peroxidase 2, a Selenoprotein Exhibiting a Dual Personality in Preventing and Promoting Cancer ................... 451 Regina Brigelius-Flohé and Anna P. Kipp

39 Selenoproteins in Cardiovascular Redox Pathology ............................ 463 Diane E. Handy and Joseph Loscalzo

40 What Do We Know About Selenium Contributions to Muscle Physiology? ............................................................................. 475 Alain Lescure , Mickaël Briens , and Ana Ferreiro

41 Tissue-Specifi c Regulation of Thyroid Status by Selenodeiodinases ............................................................................... 487 Alessandro Marsili , P. Reed Larsen , and Ann Marie Zavacki

42 The Role of Selenoproteins in Resolution of Infl ammation ................ 499 Bastihalli T. Diwakar , Emily R. Finch , Chang Liao , Ashley E. Shay , and K. Sandeep Prabhu

43 Glutathione Peroxidase 4 and Ferroptosis ............................................ 511 José Pedro Friedmann Angeli , Bettina Proneth , and Marcus Conrad

44 Mutations in Humans That Adversely Affect the Selenoprotein Synthesis Pathway .................................................... 523 Erik Schoenmakers , Nadia Schoenmakers , and Krishna Chatterjee

45 Alteration of Selenoprotein Expression During Stress and in Aging............................................................................................. 539 Zahia Touat-Hamici , Yona Legrain , Jordan Sonet , Anne-Laure Bulteau , and Laurent Chavatte

Part V Biological Models for Elucidating the Role of Selenium and Selenoproteins in Biology and Medicine

46 Selenocysteine tRNA[Ser]Sec Mouse Models for Elucidating Roles of Selenoproteins in Health and Development ........................... 555 Bradley A. Carlson

47 Mouse Models that Target Individual Selenoproteins ......................... 567 Marcus Conrad and Ulrich Schweizer

Contents

xxi

48 The Naked Mole Rat and Selenium ....................................................... 579 Alexei V. Lobanov and Vadim N. Gladyshev

49 Glutathione Peroxidase 1: Models for Diabetes and Obesity .............. 587 Xin Gen Lei and Marko Vatamaniuk

50 Selenium in Livestock and Other Domestic Animals .......................... 595 Peter F. Surai and Vladimir I. Fisinin

Index ................................................................................................................. 607

Contents

xxiii

Contributors

Houssni Abid Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Ifat Alsharif Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

José Pedro Friedmann Angeli Helmholtz Zentrum München , Institute of Developmental Genetics , Neuherberg , Germany

Youssef Anouar Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Elias S.J. Arnér Division of Biochemistry, Department of Medical Biochemistry and Biophysics , Karolinska Institutet , Stockholm , Sweden

Annalisa Bargellini CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center , University of Modena and Reggio Emilia , Modena , Italy

Marianna K. Baum Department of Dietetics and Nutrition, Stempel College of Public Health and Social Work , Florida International University , Miami , FL , USA

Marla J. Berry Department of Cell and Molecular Biology, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA

Katarzyna Bierla CNRS-UPPA, UMR 5254 , Laboratoire de Chimie Analytique Bio-inorganique et Environnement (LCABIE-IPREM) , Pau , France

Paola Borella CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center , University of Modena and Reggio Emilia , Modena , Italy

Valentina Bosello-Travain Department of Molecular Medicine , University of Padova , Padova , Italy

xxiv

Loubna Boukhzar Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Mickaël Briens Architecture et Réactivité de l’ARN, CNRS , Université de Strasbourg , Strasbourg , France

Adisseo France S.A.S., Centre for Expertise and Research in Nutrition , Commentry , France

Regina Brigelius-Flohé German Institute of Human Nutrition Potsdam- Rehbrücke , Nuthetal , Germany

Anne-Laure Bulteau Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, LCABIE , IPREM, CNRS/UPPA, UMR5254 , Pau , France

Institut de Génomique Fonctionelle de Lyon, IGFL , CNRS/ENS UMR5242 , Lyon , France

Barbara Burlingame School of Public Health , Massey University , Wellington , New Zealand

Adriana Campa Department of Dietetics and Nutrition, Stempel College of Public Health and Social Work , Florida International University , Miami , FL , USA

Bradley A. Carlson Molecular Biology of Selenium Section, Mouse Cancer Genetics Program , Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA

Dorthe Cartier Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Sergi Castellano Department of Evolutionary Genetics , Max Planck Institute for Evolutionary Anthropology , Leipzig , Germany

Matthieu Castex Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Abdeslam Chagraoui Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , INSERM U982, Normandy University of Rouen , Mont-Saint-Aignan , France

Krishna Chatterjee Wellcome Trust–MRC Institute of Metabolic Science , University of Cambridge , Cambridge , UK

Laurent Chavatte Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, LCABIE, IPREM , CNRS/UPPA, UMR5254 , Pau , France

Centre International de Recherche en Infectiologie, CIRI , Lyon , France

INSERM U1111 , Lyon , France

CNRS/ENS UMR5308 , Lyon , France

Contributors

xxv

Gerald F. Combs Jr. Jean Mayer USDA Human Nutrition Research Center on Aging , Tufts University , Boston , MA , USA

Marcus Conrad Helmholtz Zentrum München, Institute of Developmental Genetics , Neuherberg , Germany

Paul R. Copeland Department of Biochemistry and Molecular Biology , Rutgers - Robert Wood Johnson Medical School , Piscataway , NJ , USA

Giorgio Cozza Department of Molecular Medicine , University of Padova , Padova , Italy

Rebecca N. Dardashti Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Linoy Dery Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Shahar Dery Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Alan M. Diamond Department of Pathology , University of Illinois at Chicago , Chicago , IL , USA

Bastihalli T. Diwakar Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis , The Pennsylvania State University , University Park , PA , USA

Malgorzata Dobosz-Bartoszek Department of Biochemistry and Molecular Genetics, College of Medicine , University of Illinois at Chicago , Chicago , IL , USA

Nobuyoshi Esaki Kyoto Study Center , The Open University of Japan , Kyoto , Japan

Anthony Falluel-Morel Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint-Aignan , France

Ana Ferreiro Pathophysiology of Striated Muscles Laboratory, Unit of Functional and Adaptive Biology (BFA) , University Paris Diderot, Sorbonne Paris Cité, BFA, UMR CNRS 8251 , Paris , Cedex 13 , France

INSERM U787, Myology Group, Institut de Myologie , Groupe Hospitalier Pitié-Salpêtrière , Paris , France

UPMC, UMR787 , Paris , France

AP-HP, Centre de Référence Maladies Neuromusculaires Paris-Est , Groupe Hospitalier Pitié-Salpêtrière , Paris , France

Tommaso Filippini CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center , University of Modena and Reggio Emilia , Modena , Italy

Contributors

xxvi

Emily R. Finch Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis , The Pennsylvania State University , University Park , PA , USA

Vladimir I. Fisinin Russian Academy of Science , Moscow , Russia

All-Russian Institute of Poultry Husbandry , Sergiev Posad , Russia

Leopold Flohé Departamento de Bioquímica , Universidad de la República , Montevideo , Uruguay

Sarah E. Galinn Department of Biological Sciences , Towson University , Towson , MD , USA

Vadim N. Gladyshev Division of Genetics, Department of Medicine , Brigham and Women’s Hospital, Harvard Medical School , Boston , MA , USA

Ting Gong Department of Cell and Molecular Biology, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA

Department of Molecular Biosciences and Bioengineering , University of Hawaii at Manoa , Manoa , HI , USA

Roderic Guigó Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) , The Barcelona Institute of Science and Technology , Barcelona , Catalonia , Spain

Universitat Pompeu Fabra (UPF) , Barcelona , Catalonia , Spain

Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) , Barcelona , Catalonia , Spain

Abdallah Hamieh Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint-Aignan , France

Diane E. Handy Cardiovascular Division, Department of Medicine , Brigham and Women’s Hospital and Harvard Medical School , Boston , MA , USA

Janelle M. Hartman Department of Biological Sciences , Towson University , Towson , MD , USA

Dolph L. Hatfi eld Molecular Biology of Selenium Section, Mouse Cancer Genetics Program , Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA

John Hesketh Human Nutrition Research Centre and Institute for Cell and Molecular Biosciences , Newcastle University , Newcastle-upon-Tyne , UK

School of Biomedical Sciences, Faculty of Medical Sciences, Newcastle University, The Medical School, Newcastle-upon-Tyne, UK

Contributors

xxvii

Peter R. Hoffmann John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA

Michael T. Howard Human Genetics , University of Utah , Salt Lake City , UT , USA

Anna P. Kipp German Institute of Human Nutrition Potsdam-Rehbrücke , Nuthetal , Germany

Josef Köhrle Institut für Experimentelle Endokrinologie , Charité-Universitätsmedizin Berlin , Berlin , Germany

P. Reed Larsen Thyroid Section, Division of Endocrinology, Diabetes and Hypertension , Brigham and Women’s Hospital , Boston , MA , USA

Byung Cheon Lee College of Life Sciences and Biotechnology , Korea University , Seoul , South Korea

Byeong Jae Lee School of Biological Sciences , Seoul National University , Seoul , South Korea

Yona Legrain Centre de Génétique Moléculaire , CGM, CNRS, UPR3404 , Gif- sur- Yvette , France

Xin Gen Lei Department of Animal Science , Cornell University , Ithaca , NY , USA

Alain Lescure Architecture et Réactivité de l’ARN, CNRS , Université de Strasbourg , Strasbourg , France

Chang Liao Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis , The Pennsylvania State University , University Park , PA , USA

Isabelle Lihrmann Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Jun Liu Department of Chemistry and Biochemistry , University of Delaware , Newark , DE , USA

Alexei V. Lobanov Division of Genetics, Department of Medicine , Brigham and Women’s Hospital, Harvard Medical School , Boston , MA , USA

Ryszard Lobinski CNRS-UPPA, UMR 5254, Laboratoire de Chimie Analytique Bio-inorganique et Environnement (LCABIE-IPREM) , Pau , France

Joseph Loscalzo Cardiovascular Division, Department of Medicine , Brigham and Women’s Hospital and Harvard Medical School , Boston , MA , USA

Matilde Maiorino Department of Molecular Medicine , University of Padova , Padova , Italy

Contributors

xxviii

Marco Mariotti Division of Genetics, Department of Medicine, Brigham and Women’s Hospital , Harvard Medical School , Boston , MA , USA

Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG) , The Barcelona Institute of Science and Technology , Barcelona , Catalonia , Spain

Universitat Pompeu Fabra (UPF) , Barcelona , Catalonia , Spain

Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) , Barcelona , Catalonia , Spain

Alessandro Marsili Endocrinology Unit, Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy

Sabrina Sales Martinez Department of Dietetics and Nutrition, Stempel College of Public Health and Social Work , Florida International University , Miami , FL , USA

Catherine Méplan School of Biomedical Sciences, Faculty of Medical Sciences , Newcastle University , The Medical School, Newcastle-upon-Tyne , UK

Human Nutrition Research Centre and Institute for Cell and Molecular Biosciences , Newcastle University , Newcastle-upon-Tyne , UK

Norman Metanis Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Hisaaki Mihara Department of Biotechnology, College of Life Sciences , Ritsumeikan University , Kusatsu , Shiga , Japan

Giovanni Miotto Department of Molecular Medicine , University of Padova , Padova , Italy

Reem Mousa Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Androniki Naska Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece

Alexandr A. Nikonorov Institute of Bioelementology (Russian Satellite Centre of Trace Element – Institute for UNESCO), Orenburg State University, Orenburg, Russia

Department of Biochemistry , Orenburg State Medical University , Orenburg , Russia

Laura Orian Department of Chemical Sciences , University of Padova , Padova , Italy

Jin Mo Park Cutaneous Biology Research Center , Massachusetts General Hospital and Harvard Medical School , Charlestown , MA , USA

Kristin M. Peters Department of Biological Sciences , Towson University , Towson , MD , USA

Contributors

xxix

Mark H. Pinkerton Department of Biochemistry and Molecular Biology , Rutgers - Robert Wood Johnson Medical School , Piscataway , NJ , USA

Matthew W. Pitts Department of Cell and Molecular Biology, John A. Burns School of Medicine , University of Hawaii , Honolulu , HI , USA

K. Sandeep Prabhu Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis , The Pennsylvania State University , University Park , PA , USA

Gaëtan Prevost Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Bettina Proneth Helmholtz Zentrum München, Institute of Developmental Genetics , Neuherberg , Germany

Margaret P. Rayman Department of Nutritional Sciences , University of Surrey , Guildford , UK

Post S. Reddy Institute of Chemistry , The Hebrew University of Jerusalem , Jerusalem , Israel

Michael Rother Institut für Mikrobiologie , Technische Universität Dresden , Dresden , Germany

Antonella Roveri Department of Molecular Medicine , University of Padova , Padova , Italy

Sharon Rozovsky Department of Chemistry and Biochemistry , University of Delaware , Newark , DE , USA

Rama Saad Department of Pathology , University of Illinois at Chicago , Chicago , IL , USA

Didac Santesmasses Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology , Barcelona , Catalonia , Spain

Universitat Pompeu Fabra (UPF) , Barcelona , Catalonia , Spain

Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) , Barcelona , Catalonia , Spain

Edward E. Schmidt Division of Biochemistry, Department of Medical Biochemistry and Biophysics , Karolinska Institutet , Stockholm , Sweden

Microbiology and Immunology , Montana State University , Bozeman , MT, USA

Erik Schoenmakers Wellcome Trust–MRC Institute of Metabolic Science , University of Cambridge , Cambridge , UK

Nadia Schoenmakers Wellcome Trust–MRC Institute of Metabolic Science , University of Cambridge , Cambridge , UK

Contributors

xxx

Lutz Schomburg Institut für Experimentelle Endokrinologie , Charité-Universitätsmedizin Berlin , Berlin , Germany

Ulrich Schweizer Institut für Biochemie und Molekularbiologie , Rheinische Friedrich-Wilhelms-Universität Bonn , Bonn , Germany

Ashley E. Shay Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis , The Pennsylvania State University , University Park , PA , USA

Miljan Simonović Department of Biochemistry and Molecular Genetics, College of Medicine , University of Illinois at Chicago , Chicago , IL , USA

Margarita G. Skalnaya Russian Society of Trace Elements in Medicine , ANO “Centre for Biotic Medicine” , Moscow , Russia

Anatoly V. Skalny Laboratory of Biotechnology and Applied Bioelementology , Yaroslavl State University , Yaroslavl , Russia

Russian Society of Trace Elements in Medicine , ANO “Centre for Biotic Medicine” , Moscow , Russia

Institute of Bioelementology (Russian Satellite Centre of Trace Element – Institute for UNESCO) , Orenburg State University , Orenburg , Russia

All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR) , Moscow , Russia

Jordan Sonet Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, LCABIE, IPREM, CNRS/UPPA, UMR5254 , Pau , France

Roger A. Sunde Department of Nutritional Sciences , University of Wisconsin , Madison , WI , USA

Peter F. Surai Trakia University , Stara Zagora , Bulgaria

Szent Istvan University , Godollo , Hungary

Sumy National Agrarian University , Sumy , Ukraine

Odessa National Academy of Food Technology , Odessa , Ukraine

Russian Academy of Science , Moscow , Russia

Joanna Szpunar CNRS-UPPA, UMR 5254, Laboratoire de Chimie Analytique Bio-inorganique et Environnement (LCABIE-IPREM) , Pau , France

Yannick Tanguy Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982 , University of Rouen Normandy , Mont-Saint- Aignan , France

Alexey A. Tinkov Laboratory of Biotechnology and Applied Bioelementology , Yaroslavl State University , Yaroslavl , Russia

Institute of Bioelementology (Russian Satellite Centre of Trace Element – Institute for UNESCO), Orenburg State University , Orenburg , Russia

Department of Biochemistry , Orenburg State Medical University , Orenburg , Russia

Contributors

xxxi

Ryuta Tobe Department of Biotechnology, College of Life Sciences , Ritsumeikan University , Kusatsu , Shiga , Japan

Stefano Toppo Department of Molecular Medicine , University of Padova , Padova , Italy

Zahia Touat-Hamici Centre de Génétique Moléculaire, CGM, CNRS, UPR3404 , Gif-sur-Yvette , France

Petra A. Tsuji Department of Biological Sciences , Towson University , Towson , MD , USA

Fulvio Ursini Department of Molecular Medicine , University of Padova , Padova , Italy

Marko Vatamaniuk Department of Animal Science , Cornell University , Ithaca , NY , USA

Marco Vinceti CREAGEN - Environmental, Genetic and Nutritional Epidemiology Research Center , University of Modena and Reggio Emilia , Modena , Italy

Louise White Department of Evolutionary Genetics , Max Planck Institute for Evolutionary Anthropology , Leipzig , Germany

Lin Yan Grand Forks Human Nutrition Research Center , USDA-ARS , Grand Forks , ND , USA

Mattia Zaccarin Department of Molecular Medicine , University of Padova , Padova , Italy

Ann Marie Zavacki Thyroid Section, Division of Endocrinology, Diabetes and Hypertension , Brigham and Women’s Hospital , Boston , MA , USA

Yan Zhang Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University , Shenzhen , China

Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences , Chinese Academy of Sciences , Shanghai , China

Contributors