SELENIUM Its Molecular Biology and Role in Hum Health
SELENIUM Its Molecular Biology and Role in Human
Health
The Cover shows the genetic code emphasizing how selenium has altered our understanding of the code by its insertion into protein as the amino acid, selenocysteine (Sec), that is dictated by UGA. The background shows the increased histopathology of lung tissue five days post influenza infection of a selenium-deficient mouse (see page 242).
SELENIUM Its Molecular Biology and Role in Human
Health
edited by
Dolph L. Hatfield National Cancer Institute, U.S.A.
SPRINGER SCIENCE+BUSINESS MEDIA, L L C
Library of Congress Cataloging-in-Publication
Selenium : its molecular biology and role in human health / edited by Dolph L . Hatfield, p. cm. Includes bibliographical references and index. ISBN 978-1-4613-5639-4 ISBN 978-1-4615-1609-5 (eBook) DOI 10.1007/978-1-4615-1609-5 1. Selenium—Health aspects. 2. Selenium—Physiological effect. 3. Selenium in
human nutrition. I. Hatfield, Dolph L.
QP535.S5 S445 2001 621' .01524-dc21 2001020364
Copyright ° 2001 by Springer Science+Business Media New York. Second Printing 2003. Originally published by Kluwer Academic Publishers in 2001
This printing is a digital duplication of the original edition.
Al l rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo-copying, recording, or otherwise, without the prior written permission of the publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.
Printed on acid-free paper
DEDICATION
to my wife, Mary Wilson Hatfield
to my grandchildren, Amber Nicole Hatfield, Logan Alexa
Hatfield and Tristan Lee Clubb.
TABLE OF CONTENTS
List of Contributors .................................................................... xi
Foreword .•....•....................................................................... xv Raymond F. Burk
Preface .......•.•.................••...•.....•................... I.' ••••••••••••••••••• xvii Dolph L. Hatfield
Acknowledgements ...•. II •••••••••••••••••••••••••••••••••••••••••••••••••••••••••• xix
Chapter 1 Introduction .•................................................. 1 ••••••••••••••••••••••••• 1 Dolph L. Hatfield
Part I. Biosynthesis of selenocysteine and its incorporation into protein
Chapter 2 Selenium metabolism in bacteria ................................................. 7 August BiXk
Chapter 3 Mammalian selenocysteine tRNA ......................•........................ 23 Bradley A. Carlson, F. Javier Martin-Romero, Easwari Kumaraswamy, Mohamed E. Moustafa, Huijun Zhi, Dolph L. Hatfield and Byeong Jae Lee
Chapter 4 Selenophosphate - selenium donor for protein and
tRNA •.••..•.•••.•.......••...•...............................•...............••........ 33 Gerard M Lacourciere
Chapter 5 SECIS elements ......•.•....•....•.........•.....•................••...•.•............ 45 Glover W. Martin, III and Marla J. Berry
viii Selenium: Its molecular biology and role in human health
Chapter 6 SECIS binding proteins ........................................................... 55 Paul R Copeland and Donna M Driscoll
Chapter 7 Towards a mechanism for selenocysteine incorporation in
eukal'Y'otes •••.•••.•••..••••••.••.••••••••••.•.•••••••..•.••.••.•••••.••••.•........... 69 John B. Mansell and Marla J. Berry
Chapter 8 Regulation ofselenoprotein expression ........................................ 81 Roger A. Sunde
Part II. Selenium-containing proteins
Chapter 9 Identity, evolution and function ofselenoproteins and
selenoprotein genes ................................................................. 99 Vadim N Gladyshev
Chapter 10 Bacterial selenoenzymes and mechanisms of action ••••••.•.•••..•...••...• 115 Thressa C. Stadtman
Chapter 11 Selenoprotein P ..................................................................... 123 Kristina E. Hill and Raymond F. Burk
Chapter 12 Selenoprotein W: A muscle protein in search ofa function ............................................................................ 137
L. Walt Ream, William R Vorachek and Phillip D. Whanger
Chapter 13 The 15 kDa selenoprotein (Sep15): functional studies
and a role in cancer etiology .................................................. 147 Vadim N Gladyshev, Alan M Diamond and Dolph L. Hatfield
Table of Contents IX
Chapter 14 Selenoproteins of the glutathione system .................................... 157 Leopold Flohe and Regina Brigelius-Flohe
Chapter 15 Selenoproteins of the thioredoxin system .••.•.....•..••..••..•••••..•.•••.•• 179 Arne Holmgren
Chapter 16 Selenium, deiodinases and endocrine function •••••..•••.•....•.•••••.•••• 189 Donald L. St. Germain
Part III. Selenium and human health
Chapter 17 Selenium as a cancer preventive agent ....................................... 205 Gerald F. Combs, Jr. and Junxuan Lii
Chapter 18. Selenium deficiency and human disease ..................................... 219 Ruth J. Coppinger and Alan M Diamond
Chapter 19 Selenium as an antiviral agent ••••••••••••••••••••.•••••.•••••••••••.•••••••••• 135 Melinda A. Beck
Chapter 20 Role of selenium in HIV I AIDS ••••••••••••••••••••••••••••••••••••.••...••••••. 247 Marianna K. Baum, Adriana Campa, Maria Jose Miguez-Burbano, Ximena Burbano and Gail Shor-Posner
Chapter 21 Effects ofselenium on immunity and aging •......••••.•......••.••..•..•••• 257 Roderick C. McKenzie, Teresa S. Rafferty, Geoffrey J. Beckett and John R. Arthur
x Selenium: Its molecular biology and role in human health
Chapter 22 Selenium and male reproduction .............................................. 273 Leopold Flohtf, Regina Brigelius-Flohtf, Matilde Maiorino, Antonella Roveri, Josef Wissing and Fulvio Ursini
Chapter 23 Role of low molecular weight, selenium-containing compounds in human health .................................... 283
Henry J. Thompson
Chapter 24 Evolution of human dietary standards for selenium ............................................................................ 299
Orville A. Levander
Chapter 25 Selenium in biology and human health: controversies and perspectives .................................................................. 313
Vadim N. Gladyshev
Index ................................................................................. 319
CONTRIBUTORS
John R. Arthur Division of Cell Integrity Rowett Research Institute,
Bucksbum Aberdeen, Scotland AB21 9SB,
UK
Mariana K. Baum Division of Metabolism and
Disease Prevention Department of Psychiatry and
Behavioral Sciences University of Miami School of
Medicine Miami, FL 33136, USA
Melinda A. Beck Department of Pediatrics and
Nutrition University of North Carolina at
Chapel Hill Chapel Hill, NC 27599, USA
Geoffrey J. Beckett Department of Clinical
Biochemistry University of Edinburgh Edinburgh, Scotland, EH3 9YW,
UK
Marla J. Berry Thyroid Division Brigham and Women's Hospital
and the Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School Boston, MA 02115, USA
August Bock Lehrstuhl fUr Mikrobiologie der
Universitat Miichen D-80638 Munich, Germany
Regina Brigelius-Flohe Department of Vitamins and
Atherosclerosis German Institute for Research of
Nutrition (DIfE) Arthur-Scheunert-Allee 114-116 D-14558 Potsdam, Germany
Ximena Burbano Division of Metabolism and
Disease Prevention Department of Psychiatry and
Behavioral Sciences University of Miami School of
Medicine Miami, FL 33136, USA
Raymond F. Burk Department of Medicine Vanderbilt University School of
Medicine Nashville, TN 37232, USA
Adriana Campa Division of Metabolism and
Disease Prevention Department of Psychiatry and
Behavioral Sciences University of Miami School of
Medicine Miami, FL 33136, USA
xii Selenium: Its molecular biology and role in human health
Bradley A. Carlson Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892 USA
Gerald F. Combs, Jr. Division of Nutritional Sciences Cornell University Ithaca, NY 14853, USA
Paul R. Copeland Department of Cell Biology Lerner Research Institute Cleveland Clinic Foundation Cleveland, OH 44195, USA
Ruth J. Coppinger Department of Human Nutrition University of Illinois at Chicago Chicago, IL 60612, USA
Alan M. Diamond Department of Human Nutrition University of Illinois at Chicago Chicago, IL 60612, USA
Donna M. Driscoll Department of Cell Biology Lerner Research Institute Cleveland Clinic Foundation Cleveland, OH 44195, USA
Leopold Flohe Department of Biochemistry Technical University of
Braunschweig Mascheroder Weg 1 D-38124 Braunschweig, Germany
Vadim N. Gladyshev Department of Biochemistry University of Nebraska Lincoln, NE 68588, USA
Dolph L. Hatfield Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892, USA
Kristina E. Hill Department of Medicine Vanderbilt University School of
Medicine Nashville, TN 37232, USA
Arne Holmgren Medical Nobel Institute for
Biochemistry Department of Medical
Biochemistry and Biophysics Karolinska Institute SE-171 77 Stockhom, Sweden
Easwari Kumaraswamy Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892, USA
Gerard M. Lacourciere Laboratory of Biochemistry National Heart, Lung, and Blood
Institute National Institutes of Health Bethesda, MD 20892, USA
Contributors
Byeong Jae Lee Laboratory of Molecular Genetics Institute for Molecular Biology
and Genetics Seoul National University Seoul 151-742, Korea
Orville A. Levander Beltsville Human Nutrition
Research Center U.S. Department of Agriculture Agricultural Research Service Beltsville, MD 20705, USA
Junxuan Lii AMC Cancer Center 1600 Pierce Street Denver, CO 80214, USA
Matilde Maiorino Dipartimento di Chimica
Biologica Universita di Padova Viale G. Colombo 3 1-35121, Padova, Italy
John B. Mansell Thyroid Division Brigham and Women's Hospital
and the Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School Boston, MA 02115, USA
Glover W. Martin, HI HarvardlMIT Division of Health
Sciences and Technology, and the Department of Microbiology and Molecular Genetics
Harvard Medical School Cambridge, MA, 02139, USA
XIll
F. Javier Martin-Romero Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892 USA
Roderick C. McKenzie Department of Medical and
Radiological Sciences University of Edinburgh Edinburgh, Scotland, EH3 9YW,
UK
Maria Jose Miguez-Burbano Division of Metabolism and
Disease Prevention Department of Psychiatry and
Behavioral Sciences University of Miami School of
Medicine Miami, FL 33136, USA
Mohamed E. Moustafa Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892, USA
Teresa S. Rafferty Department of Medical and
Radiological Sciences University of Edinburgh Edinburgh, Scotland, EH3 9YW,
UK
xiv Selenium: Its molecular biology and role in human health
L. Walt Ream Departments of Microbiology and
Environmental and Molecular Toxicology
Oregon State University Corvallis, OR 97331, USA
Antonella Roveri Dipartimento di Chimica
Biologica Universita di Padova Viale G. Colombo 3 1-35121, Padova, Italy
Gail Shor-Posner Division of Metabolism and
Disease Prevention Department of Psychiatry and
Behavioral Sciences University of Miami School of
Medicine Miami, FL 33136, USA
Donald L. St. Germain Departments of Medicine and of
Physiology Dartmouth Medical School Lebanon, NH 03756, USA
Thressa C. Stadtman National Heart, Lung, and Blood
Institute National Institutes of Health Bethesda, MD 20892, USA
Roger A. Sunde F21C Nutrition Cluster Leader Professor of Nutritional Sciences
and of Biochemistry University of Missouri Columbia, MO 65211, USA
Henry J. Thompson Center for Nutrition in the
Prevention of Disease AMC Cancer Research Center Denver, CO 80214, USA
Fulvio Ursini Dipartimento di Chimica
Biologica Universita di Padova Viale G. Colombo 3 1-35121, Padova, Italy
William R. Vorachek Departments of Microbiology and
Environmental and Molecular Toxicology
Oregon State University Corvallis, OR 97331, USA
Philip D. Whanger Departments of Microbiology and
Environmental and Molecular Toxicology
Oregon State University Corvallis, OR 97331, USA
Josef Wissing Department of Biochemistry Technical University of
Braunschweig Mascheroder Weg 1 D-38124 Braunschweig, Germany
Huijun Zhi Section on the Molecular Biology
of Selenium Basic Research Laboratory National Cancer Institute National Institutes of Health Bethesda, MD 20892, USA
FOREWORD
From molecular biology to human health, selenium research is booming. It has become clear that most physiologic effects of selenium are exerted by selenoproteins. Therefore, most of the basic research on the element examines selenoprotein expression and regulation. Synthesis of a selenoprotein requires a complex process with several elements that are unique. The details of this process are emerging from the work of a number of groups.
The significance of selenium to human health is a hot topic. There is little or no selenium deficiency in the USA, but large numbers of people elsewhere in the world are selenium deficient. Animal studies have shown that selenium deficiency in the host can modify the course of viral infections and cause mutations in the virus. Whether this occurs in human beings will be important to determine. Such selenium deficiency induced mutations could possibly be responsible for emergence of new viral strains.
Evidence has been presented from studies in animals that selenium has anticancer effects when given in pharmacologic amounts. An intervention study in human beings has supported this idea. A number of intervention studies are currently being pursued in this important, but difficult area.
The selenium field has not always been so active. Selenium came to the notice of biologists in the 1930s when it was discovered to be the dietary substance responsible for hair and hoof loss in animals grazing certain areas of the American Great Plains. This recognition of its toxicity led the USDA to map the selenium content of forage in the USA. The map that was produced demonstrated that the selenium content of plants varied tremendously according to where they were grown. Most areas of the country produced plants that contained a moderate (non-toxic) concentration of selenium. However, a few locales were distinctly different. Some produced plants that had very high selenium contents (toxic) and some produced plants that had very low selenium contents. Thus, the effort to locate high-selenium areas in order to prevent selenium toxicity in animals led also to the identification of low-selenium areas.
After selenium had been shown to be an essential nutrient in the mid-1950s, some veterinary disease endemic to areas that had been identified as low in selenium on the USDA selenium map were investigated. White muscle disease in sheep responded to selenium and thus was classed as a selenium deficiency disease. Several other pathological conditions that were vitamin E responsive, including mulberry heart disease of pigs, also responded to selenium. The association of the two nutrients in these conditions linked vitamin E with selenium and suggested that selenium
XVI Selenium: Its molecular biology and role in human health
might function as an oxidant defense because vitamin E was known to be an antioxidant.
In the early 1970s, Chinese workers investigating the cause of a childhood cardiomyopathy called Keshan disease took note of the veterinary literature of selenium deficiency diseases. Keshan disease only occurred in certain areas of China and the investigators noted that animals in those areas had clinical illnesses that were similar to those caused by selenium deficiency. They determined that hair selenium was low in the children with Keshan disease. Then they carried out a placebo-controlled study of selenium administration to children at risk for Keshan disease. Children that received selenium were protected from Keshan disease. Thus, a manifestation of selenium deficiency in human beings is a susceptibility to cardiomyopathy in children. A second (and unknown) factor is needed to cause the disease as not all selenium deficient children develop it. It is not known whether selenium deficiency has other adverse effects on human health but this is an important topic for further research. Efforts in the 1930s and 1940s to understand selenium biochemistry and
metabolism focused on mechanisms of its toxicity and excretion. However, the realization in the 1950s that selenium was an essential nutrient led to investigations of its role in normal biochemistry. Selenium deficiency was induced in experimental animals by feeding them a low selenium diet. Then biochemical systems were studied in selenium deficient animals and in controls. Using this approach, a group at the University of Wisconsin identified glutathione peroxidase as the first animal selenoenzyme in 1973. This solidified the nutritional essentiality of selenium and supported the idea that it provided defense against oxidative injury.
After almost a decade as the only know animal selenoprotein, glutathione peroxidase was joined by selenoprotein P in 1982 and by other selenoproteins soon thereafter. Presently, approximately 15 animal selenoproteins are known and that number is rising as new ones are discovered.
Studies in bacteria yielded more selenoproteins and led to the pioneering work by the Munich group in the late 1980s that elucidated the mechanism of selenoprotein synthesis in bacteria. Their work served as the starting point of the work on selenoprotein synthesis in animals.
This book is an up-to-date collection of research summaries and reviews written by active selenium researchers. Its coverage is broad with detailed basic science reviews as well as health related chapters. This book will provide an in depth summary of the field of selenium as well as a guide for future research.
Raymond F. Burk
PREFACE
Research over the last 30 years involving selenium biology has yielded new and surprising insights into biochemical, molecular and genetic aspects of this fascinating element. During this same time period, data have also been obtained from both human and animal nutritional studies suggesting a vital role for selenium in disease incidence and severity. These two disciplines of study are beginning to merge and the interrelationships between the different observations are becoming apparent as is discussed in this book.
An active area of selenium research has been the functional characterization of selenoproteins. While several chapters in this book deal with this significant topic, there is, in fact, considerable debate in the selenium field whether selenoproteins or low molecular weight selenium compounds are responsible for the many reported beneficial effects of dietary selenium. Both viewpoints are expressed herein, so that the reader will have an opportunity to see how different leaders in the field view the topic of selenium and human health, and, at the same time, obtain a more comprehensive appreciation of the present status of the thinking on these subjects.
Diet plays an extremely important role in health and disease. For example, an increasing number of health professionals contend that environmental factors such as infection, unbalanced diets, smoking, excessive alcohol consumption and insufficient exercise contribute more to chronic disease in man than genetic disposition. These maladies include cancer, cardiovascular disease, diabetes and liver dysfunction. The origins of these diseases may be attributed, at least in part, to disruption of redox homeostasis, leading to the presence of excess reactive oxygen species and oxidative damage of essential cellular components, including nucleic acids and proteins. As dietary selenium is viewed as a potent regulator of cellular redox homeostatis, selenium may be an important dietary contributor to reducing the incidence of many debilitating disorders. Although the specific biological mechanisms of selenium that are responsible for promoting better health, and the extent to which this element is involved in promoting better health, remain to be established, the available data suggest that the benefits of dietary selenium are highly significant. Caution must be exercised, however, in touting the advantages of this element as too much selenium in the diet can have toxic consequences and the range between too little and too much selenium is not much more than an order of magnitude. The guidelines for the recommended daily allowance in humans have recently been revised and are discussed in this book.
Combs and Combs wrote in 1986 that "One of the most important discoveries in nutrition in the last 30 years has been the recognition of the
XVlll Selenium: Its molecular biology and role in human health
essentiality of the element selenium ..... " (GF Combs, SB Combs 1986 The Role of Selenium in Nutrition Academic Press, Inc New York). This statement was motivated by evidence that adequate dietary selenium has important health benefits that were primarily observed in laboratory animals and livestock. These findings followed the initial observations in the mid 1950s that selenium had a role in bacterial metabolism and in preventing liver necrosis in rats. Combs and Combs also noted in 1986 that the livestock industry had prevented losses estimated in the 100s of millions of dollars by supplementing the diet of livestock with selenium or with selenium and vitamin E. Today, these savings are in the billions of dollars.
In the last 15 years, many of the molecular mysteries surrounding selenium have been solved. We now know that selenium is incorporated into protein as selenocysteine, the 21 sl naturally occurring amino acid in protein. Unlike any of the other 20 amino acids that are present in protein, the biosynthesis of selenocysteine occurs on its transfer RNA. The donation of selenocysteine to the growing selenopeptide in protein synthesis requires a novel mRNA binding protein and a selenocysteine-tRNA specific elongation factor in archaea and eukaryotes, while a single protein carries out both these functions in eubacteria. Selenoproteins have clearly evolved to take advantage of the fact that the pKa of selenocysteine is lower than the physiological pH and, therefore, this amino acid residue is ideally suited to participate in redox reactions. This and other chemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes.
As discussed in the chapters in this book, a large body of evidence indicates that selenium is a cancer chemopreventive agent. Further evidence points to a role of this element in reducing viral expression, in preventing heart disease, and other cardiovascular and muscle disorders, and in delaying the progression of AIDS in HIV infected patients. Selenium may also have a role in mammalian development, in male fertility, in immune function and in slowing the aging process. If dietary selenium does indeed influence these diseases and cellular processes, then the significance of including adequate amounts of this element in the diet may be regarded as one of the more important discoveries in nutrition in the last century.
Dolph L. Hatfield
ACKNOWLEDGMENTS
The support and generous help of Va dim N. Gladyshev and
Bradley A. Carlson throughout the preparation of this book
are gratefully acknowledged.