EXS Experientia Supplementum Vol. 52

Springer Basel AG

Metallothionein II Proceedings of the «Second International Meeting on Metallothionein and Other Low Molecular Weight Metal-binding Proteins», Ziirich, August 21-24, 1985

1987

Edited by

Jeremias H.R. Kagi Yutaka Kojima

Springer Basel AG

IUB Symposium No. 148

CIP-Kurztitelaufnahme der Deutschen Bibliothek

Metallothionein : proceedings of the ... Internat. Meeting on Metallothionein and Other Low Molecular Weight Metal-binding Proteins.

1 mit d. Erscheinungsorten Basel, Boston, Stuttgart NE: International Meeting on Metallothionein and Other Low Molecular Weight Metal Binding Proteins 2. Ziirich, August 21-24, 1985.- 1987.- ca. 702 S. (Experientia : Supplementum ; Voi. 52) (IUB sympo­sium ; No. 148) ISBN 978-3-0348-6786-3

NE: Experientia 1 Supplementum; International Union of Biochemistry: IUB symposium

Ali rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner.

© 1987 Springer Basel AG Originally published by Birkhiiuser Verlag Basel in 1987 Softcover reprint of the hardcover lst edition 1987

ISBN 978-3-0348-6786-3 ISBN 978-3-0348-6784-9 (eBook)

DOI 10.1007/978-3-0348-6784-9

v

PREFACE

Metallothioneins, ubiquitous low molecular weight proteins of extremely high metal and sulfur content, are of great interest to various branches of the life sciences ranging from bioinorganic chemistry to biochemistry, molecular biology, physiology, toxicology environmental science and medicine. They are believed to play a pivotal role in reg- ' ulating the flow of the essential trace elements zinc and copper through the cell and in modulating the harmful environmental influences of toxic metals and of various stress conditions. Since the first international meeting held on this subject in 1978 the knowledge of the structure and the function of these proteins has been deepened and extended to molecular dimensions. Thus, the spatial structure of the protein and the mode of metal binding have now been established by x-ray diffraction and advanced NMR and optical techniques. The discovery and identification of unique genetic switching mechanisms opened the way for an understanding of the characteristic in­ducibility of this protein by metals and hormones and led to the utilization of the metallothionein genes as regulatory devices in genetic engineering and in transgenic experiments.

The Second International Meeting on Metallothionein and Other Low Molecular Weight Metal-binding Proteins held in Zurich, Switzerland, from August 21 - 24, 1985, was arranged as an official Satellite Meeting - IUB Symposium If 148 - of the 13th Inter­national Congress of Biochemistry, Amsterdam, The Netherlands, and hosted by the Institute of Biochemistry of the University of Zurich. It was sponsored jointly by the International Union of Biochemistry (IUB), the International Union for Pure and Applied Biophysics (IUPAB), the World Health Organization (WHO), the Scientific C.ommittee on the Toxicology of Metals under the Permanent Commission and International Asso­ciation of Occupational Health, the Schweizerischer Nationalfonds, the Schweizerische Naturforschende Gesellschaft, the National Academy of Sciences (USA), the Biological Division of the American Chemical Society, the Society of Toxicology (USA), and the biochemical societies of various countries (American Society of Biological Chemists, Australian Biochemical Society, Gesellschaft fUr Biologische Chemie (Germany), the Japanese Biochemical Society, and the Schweizerische Gesellschaft fUr Biochemie.

The meeting was attended by about 200 scientists from 21 countries including repre­sentatives from the International Programme on Chemical Safety of WHO, the Metals Specialty Section of the Society of Toxicology (USA), and the Scientific Committee on the Toxicology of Metals under the Permanent Commission and International Associa­tion of Occupational Health. The Introductory Lecture was given by the Honorary President, Professor Bert L. Vallee, on the topic "Implications of Metallothionein Chemistry". The scientific contributions were organized in six symposia, six colloquia and poster presentations and discussions.

This book comprises the proceedings of the meeting. Part I contains the introductory lecture, recommendations on the nomenclature on metallothionein and solicited review articles on the biochemical, molecular -biological, physiological, and toxicological aspects of metallothionein intended to facilitate access to this interdisciplinary field. Part II consists of contributions in symposia, colloquia and poster discussions. Part III contains the program of the meeting and the poster abstracts.

On behalf of the organizer and the participants, we acknowledge the generous finan­cial support received from the Schweizerischer Nationalfonds, the Schweizerische Na­turforschende Gesellschaft, the Union Schweizerischer Gesellschaften fUr Experimen­telle Biologie, the Erziehungsdirektion des Kantons Zurich, the Krebsliga des Kantons

VI

Zurich, the National Institute of Environmental Health Sciences (USA), the United States Department of Energy, the International Union of Biochemistry (IUS), the International Union for Pure and Applied Biophysics (IUPAB), and the Society of Toxicology Metals Specialty Section (USA). Our sincere thankfulness also goes to the University of Zurich for providing the facilities for the meeting.

We also acknowledge the assistance of the editorial staff of Birkhauser Verlag, Basel/ Boston/Stuttgart. Special thanks also to Ms. Genia de Vallier for her devoted effort in the preparation and organization of the meeting and in the production of this vol­ume.

April, 1987

Jeremias H.R. Kagi

Yutaka Kojima

TABLE OF CONTENTS

Preface

Part I

Lecture by the Honorary President

Implications and Inferences of Metallothionein Structure B.L. Vallee

Recommendations on Nomenclature of Metallothionein

Nomenclature of Metallothionein B.A. Fowler, C.E. Hildebrand, Y. Kojima, and M. Webb

Reviews on Metallothionein

Chemistry and Biochemistry of Metallothionein J.H.R. Kagi and Y. Kojima

Molecular Biology of Metallothionein Gene Expression R.D. Palmiter

Nutritional and Physiological Significance of Metallothionein I. Bremner

Toxicological Significance of Metallothionein M. Webb

Part II

3

5

17

19

23

25

63

81

109

Chemical Structure of Metallothionein 137

Crystal Structure of Cd,Zn Metallothionein 139 W.F. Furey, A.H. Robbins, L.L. Clancy, D.R. Winge, B.C. Wang, and C.D. Stout

Spatial Structure of Rabbit Liver Metallothionein-2 149 in Solution by NMR

G. Wagner, M.H. Frey, D. Neuhaus, E. Wi:irgi:itter, w. Braun, M. vasak, J.H.R. Kagi, and K. Wuthrich

NMR Analysis of the Structure and Metal Sequestering 159 Properties of Metallothioneins

I.M. Armitage, D.C. Dalgarno, and B.A. Johnson

Interprotein Metal Exchange Reactions of Metallothionein 171 J.D. Otvos, H.R. Engeseth, D.G. Nettesheim, and C.R. Hilt

Spectroscopic and Chemical Approaches to the Study of 179 Metal-Thiolate Clusters in Metallothionein (MT)

M. Vasak, J. Overnell and M. Good

VII

VIII

Probing the Reactivity of the Zinc and Cadmium Ions 191 Bound to Rabbit Liver Metallothloneins with EDT A

J.K. Nicholson, P.J. Sadler and M. Vasak

Information on Metal Binding Properties of Metallothioneins 203 from Optical Spectroscopy

M.J. Stillman, A.Y.C. Law, W. Cai, and A.J. Zelazowski

Copper Coordination in Metallothionein 213 D.R. Winge

Structural and Functional Aspects of Metal-Thiolate 219 Centres in Metallothionein

U. Weser

EXAFS Studies of Metallothionein 227 S.S. Hasnain, G.P. Diakun, I. Abrahams, I. Ross, C.D. Garner, I. Bremner, and M. Vasak

Luminescence Emission from the Cu(I)-Thiolate Complex 237 in Metallothioneins

M. Beltramini, K. Munger, U.A. Germann, and K. Lerch

Cadmium Binding and Metal Cluster Formation in 243 Metallothionein: A Differential Modification Study

w .R. Bernhard, M. Va~ak and J.H.R. Kagi

Metallothionein: A Bifunctional Chelator for the 247 Radiolabeling of Biologically Active Molecules

M.M. Morelock and G.L. Tolman

Biochemistry of Metallothionein 255

Human Hepatic Metallothioneins: Resolution of Six Isoforms 257 P.E. Hunziker and J.H.R. Kagi

Quantification and Characterization of Metallothioneins 265 in Tissues of Lower Vertebrates and Invertebrates

K.T. Suzuki

Cadmium-Binding Proteins in Rat Testes: Characterization 273 and Apparent Source of the Low-Molecular-Weight Protein

C.D. Klaassen and M.P. Waalkes

Low Molecular Weight Cadmium and Selenium Containing 281 Proteins Unlike Metallothionein in Animals

P.O. Whanger, J.T. Deagen and M.A. Beilstein

Characterization of Metallothionein-Like Protein in Rat Brain 289 M. Ebadi and S. Swanson

Cadmium Resistance in Drosophila: A Small Cadmium Binding 293 Substance

K.B. Jacobson, M.W. Williams, L.J. Richter, S.E. Holt, G.J. Hook, S.M. Knoop, F.V. Sloop, and J.B. Faust

The Cd-Binding Protein from Tomato Compared to those 301 of Other Vascular Plants

W.E. Rauser

Purification and Characterization of Atypical 309 Cadmium-Binding Polypeptides from Zea Mays

W .R. Bernhard and J.H.R. Kagi

Phytochelatins, the Heavy Metal Binding Peptides of Plants: 317 Characterization and Sequence Determination

E. Grill

Characterization of Metal Binding Peptides from 323 Cadmium Resistant Plant Cells

N.J. Robinson, K. Barton, C.M. Naranjo, L.O. Sillerud, J. Trewhella, K. Watt, and P.J. Jackson

Electrochemical Quantification and Characterization 329 of Metallothioneins

R.W. Olafson

Enzyme-Linked Immunosorbent Assay (ELISA) for 335 Metallothionein

J.S. Garvey, D.G. Thomas and H.J. Linton

Comparison of Cadmium-Saturation Assay and 343 Radioimmunoassay for the Determination of Metallothionein Concentration in Tissues

Z.A. Shaikh and C.V. Nolan

Metallothionein-Determination in Biological Materials: 351 Interlaboratory Comparison of 5 Current Methods

H.H. Dieter, L. MUller, J. Abel, and K.H. Summer

Biochemical Genetics of Metallothionein 359

Structure and Expression of the Human Metallothionein Genes 361 L. Gedamu, U. Varshney, N. Jahroudi, R. Foster, and N. W. Shworak

Rat Metallothionein Multigene Family 373 R.D. Andersen, S.J. Taplitz, B.W. Birren, G. Bristol, and H.R. Herschman

The Metallothionein Gene of Drosophila 385 G. Maroni, E. Otto, D. Lastowski-Perry, and D.H. Price

Isolation and Regulation of Expression of the Neurospora 393 crassa Copper Metallothionein Gene

K. MUnger, U.A. Germann and K. Lerch

Transcriptional Control Mechanisms which Regulate the 401 Expression of Human Metallothionein Genes

M. Karin, A. Haslinger, A. Heguy, T. Dietlin, and R. Imbra

Metal Regulatory Elements of the Mouse Metallothionein-I 407 Gene

P.F. Searle, G.W. Stuart and R.D. Palmiter

Inducible and Constitutive Sequence Elements in the 415 Enhancer of the Mouse Metallothionein-I Gene

E. Serfling and W. Schaffner

IX

X

Function and Regulation of Yeast Copperthionein 423 D.J. Thiele, C.F. Wright, M.J. Walling, and D.H. Hamer

Synaptic Relations in Meiotic Gene Conversion at the 431 Iterated CUP1r Locus of S. cerevisiae

J.W. Welch, D.H. Maloney and S. Fogel

Role of Metallothionein in Detoxification and Tolerance 439 to Transition Metals

P.C. Huang, S. Morris, J. Dinman, R. Pine, and B. Smith

Molecular and Cellular Mechanisms of Cadmium 447 Resistance in Cultured Cells

D.L. Grady, R.K. Moyzis and C.E. Hildebrand

Analysis of the Detoxification of Heavy Metal Ions by 457 Mouse Metallothionein

D.M. Durnam and R.D. Palmiter

Heavy Metal Induced Protein Synthesis in Fish Cell Lines 465 J. Price-Haughey and L. Gedamu

Injection of the Mouse MT -1 Gene into Rainbow Trout Eggs 471 and Assay of Trout Fry for Resistance to Cadmium and Zinc Toxicity

N. Maclean, C. Woodall and F. Crossley

Abnormal Copper Metabolism and Regulation of 477 Metallothionein Gene Expression in Menkes' Disease

A. Leone and D.H. Hamer

Role of Metallothionein in Metal Pathways and Cell Metabolism 481

Metallothionein in Regeneration, Reproduction and 483 Development

M. Webb

Biosynthesis and Metabolism of Metallothionein in 499 Rat during Perinatal Development

M.G. Cherian, D.M. Templeton, K.R. Gallant, and D. Banerjee

Metallothionein in Blood, Bile and Urine 507 I. Bremner, R.K. Mehra and M. Sato

Metallothioneins of Monocytes and Lymphocytes 519 S. Koizumi, T. Sane, M. Kimura, F. Otsuka, and M. Ohsawa

Synthesis and Degradation of Erythrocyte Metallothionein 525 in Cadmium-Administered Mice

K. Tanaka, K. Min, S. Onosaka, ar1d C. Fukuhara

Histological Demonstration of Immunoreactive Metallothionein 533 in Rat and Human Tissues

M.E. Elmes, J.P. Clarkson and B. Jasani

The Function of Metallothionein in Cell Metabolism 539 D.G. Thomas, A.D. Dingman and J.S. Garvey

Regulation of Liver Zinc Metabolism and Metallothionein 545 by cAMP, Glucagon and Glucocorticoids and Suppression of Free Radicals by Zinc

R.J. Cousins and D.E. Coppen

The Involvement of Catecholamines and Polypeptide 555 Hormones in the Multihormonal Modulation of Rat Hepatic Zinc Thionein Levels

F.D. Brady, B.S. Helvig, A.E. Funk, and S.H. Garrett

Induction of Synthesis and Degradation of Metallothionein-I 565 in the Tissues of Rats Injected with Zinc

R.K. Mehra and I. Bremner

Cadmium-Zinc Interactions in the Ehrlich Cell: 573 Metallothionein and other Sites

D.H. Petering, S. Krezoski, J. Villalobos, C.F. Shaw III, and J.D. Otvos

Effects of Type I Interferon-Inducing Agents on Hepatic 581 Metallothionein

J.U. Bell, M.J.P. Lawman, J.M. Lopez, L.E. DesJardin, and L.A.D. Applewhite

Metallothionein and Zinc Metabolism in Endotoxin Shock Rats 587 S. Abe, M. Matsumi, M. Tsukioki, S. Mizukawa, T. Takahashi, Y. Iijima, Y. Itano, and F. Kosaka

Protective Function of Metallothionein against Certain 595 Anticancer Agents

L. Endresen and H.E. Rugstad

Alteration of Radiosensitivity in Metallothionein Induced Mice 603 and a Possible Role of Zn-Cu-Thionein in GSH-Peroxidase System

J. Matsubara

Activation of o-Aminolevulinic Acid Dehydratase Following 613 Donation of Zinc from Kidney Metallothionein

P.L. Goering and B.A. Fowler

Role of Metallothionein in Metal Detoxification, Metal Tolerance 617 and Metal Toxicity

Role of Metallothionein in Induced Resistance to Cadmium 619 Toxicity in Isolated Rat Hepatocytes

J.M. Frazier and W .S. Din

Metallothionein Gene Expression and Cadmium Toxicity in 627 Freshwater Fish

J. Kay, M.W. Brown, A. Cryer, J.F. del.G.Solbe, D. Shurben, J.S. Garvey, and D.G. Thomas

Role of Metallothionein in Metal Detoxification and Metal 631 Tolerance in Protein Calorie Malnutrition and Calcium Deficient Monkeys (Macaca mulatta)

R. Nath, V.K. Paliwal, R. Prasad, and R. Kambadur

XI

XII

Intestinal Absorption of Cadmium and Inorganic Mercury in 639 the Rat: No Major Involvement of Metallothionein

J.K. Piotrowski, J.A. Szymar'iska, B.W. Kaszper, M. Skrzypir'iska-Gawrysiak, and S. Brzeznicki

Hepatic Lysosomal Copper-Thionein 647 I. Sternlieb

Induction of Renal Metallothionein Allows Increasing Dose of 655 an Extensively Used Antitumor Drug, cis-Diamminedichloro-platinum - ·

N. Imura, A. Naganuma, M. Satoh, and Y. Koyama

Mechanism of Cadmium-Metallothionein-Induced Nephro- 661 toxicity: Relationship to Altered Renal Calcium Metabolism

B.A. Fowler, P.L. Goering and K.S. Squibb

On the Role of Metallothionein in Cadmium Induced Renal 669 Toxicity

M. Nordberg and G.F. Nordberg

Cadmium, Zinc and Copper in Rabbit Kidney Metallothionein - 677 Relation to Kidney Toxicity

Part III

C.G. Elinder, M. Nordberg, B. Palm, L. Bjorck, and L. Jonsson

Program of the Second International Meeting on Metallothionein and Other Low Molecular Weight Metal-binding Proteins

Poster Abstracts

List of Participants

Index

Author Index

Subject Index

683

695

731

743

747