Roles of metallothionein and related proteins in metal metabolism and toxicity: problems and perspectives.

This summary examines some of the known and hypothesized roles of metallothionein and related proteins in mediating the metal metabolism and toxicity from a chemical perspective. It attempts to examine in kinetic terms how such molecules may exert homeostatic control over the intracellular bioavailability of metal ions to essential enzymatic or other molecular systems. The concept of ongoing competition between metallothionein and related proteins with other intracellular metal-binding sites for various metals is also examined in relation to the thermodynamic stability of these proteins. Comparisons between mammalian metallothionein and analogous nonmammalian proteins demonstrate both similarities and great differences in types of metal-binding sites, metal-binding constants, amino acid composition, and secondary structures such that apparent diversity of these low molecular weight metal-binding molecules in nature appears to be growing ever wider. The potential value of these data rests both in delineating new hypotheses for metallothionein evolution and in suggesting new model systems for discovering the normal function of metallothionein and related proteins in cells.

• Publication year

  1986

• Venue

  Environmental Health Perspectives

• Publication date

  1986-03-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1289/EHP.8665217PMID 3709444PMCID 1474704
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Kinetic lability of zinc bound to metallothionein in Ehrlich cells.

  1988cited by this paper
• Cadmium-zinc interactions in the Ehrlich cell: metallothionein and other sites.

  1987cited by this paper
• Nomenclature and possible evolutionary pathways of metallothionein and related proteins.

  1986cited by this paper
• Metabolism of cadmium, zinc and copper in the rat kidney: the role of metallothionein and other binding sites.

  1984cited by this paper
• Effect of epinephrine and norepinephrine on zinc thionein levels and induction in rat liver.

  1984cited by this paper
• Tumor-host zinc metabolism the central role of metallothionein

  1983cited by this paper
• Induction of kidney metallothionein and metallothionein messenger RNA by zinc and cadmium.

  1982cited by this paper
• The induced synthesis of metallothionein in various tissues of rats in response to metals. II. Influence of zinc status and specific effect on pancreatic metallothionein.

  1982cited by this paper
• Cadmium resistance correlated with cadmium uptake and thionein binding in CHO cell variants Cdr20f4 and Cdr30f9.

  1981cited by this paper
• THE INFLUENCE OF DIETARY COPPER INTAKE ON THE TOXICITY OF CADMIUM *

  1980cited by this paper
• Ligand substitution reactions of metallothioneins with EDTA and apo-carbonic anhydrase.

  1980cited by this paper
• On the sensitivity of metallothioneins to oxidation during isolation.

  1980cited by this paper
• Structure of the metal clusters in rabbit liver metallothionein.

  1980cited by this paper
• Zinc-, copper- and cadmium-binding protein in Ehrlich ascites tumour cells.

  1980cited by this paper
• Regulation of liver metallothionein and plasma zinc by the glucocorticoid dexamethasone.

  1979cited by this paper
• Some effects of oral ingestion of cadmium on zinc, copper, and iron metabolism.

  1979cited by this paper
• Effect of cadmium and lead on copper and zinc metabolism

  1979cited by this paper
• Accumulation and depletion of zinc in rat liver and kidney metallothionens.

  1977cited by this paper
• Nuclear 115cadmium: uptake and disappearance correlated with cadmium-binding protein synthesis.

  1976cited by this paper
• The metallothioneins.

  1975cited by this paper
• Biological function of metallothionein. I. Synthesis and degradation of rat liver metallothionein.

  1975cited by this paper
• Trace element metabolism in animals - 2.

  1974cited by this paper
• Alterations in hepatocytes after manipulation of the diet: copper, zinc and cadmium interactions.

  1974cited by this paper
• Biochemical effects of mercury, cadmium, and lead.

  1972cited by this paper
• The biosynthesis of apo- and metalloalkaline phosphatases of Escherichia coli.

  1968cited by this paper
• A CADMIUM PROTEIN FROM EQUINE KIDNEY CORTEX

  1957cited by this paper

• Understanding Molecular Mechanisms Driving Cadmium-Induced Mitochondrial Dysfunction in Human Metabolic Liver Disease.

  2026cites this paper
• Pharmacokinetics of metal excretion following different doses of sodium EDTA infusion

  2025cites this paper
• Multi-scale insights into the mechanisms by which nanoplastics amplify cadmium genotoxicity: Stress response, molecular regulatory pathways and molecular docking

  2025cites this paper
• The association of blood lead levels and renal effects may be modified by genetic combinations of Metallothionein 1A 2A polymorphisms

  2020cites this paper
• Polymer Hydrogels and Their Applications Toward Sorptive Removal of Potential Aqueous Pollutants

  2019cites this paper
• Effects of ocean acidification on 109Cd, 57Co, and 134Cs bioconcentration by the European oyster (Ostrea edulis): Biokinetics and tissue-to-subcellular partitioning.

  2018cites this paper
• How gut transcriptional function of Drosophila melanogaster varies with the presence and composition of the gut microbiota

  2018cites this paper
• Une meilleure caractérisation des mécanismes d’action toxique à partir de la structure moléculaire

  2017cites this paper
• Mechanisms of Kidney Cell Injury from

  2016cites this paper
• Domain Selection in Metallothionein 1A: Affinity-Controlled Mechanisms of Zinc Binding and Cadmium Exchange.

  2015cites this paper
• BIOMARCADORES DE EXPOSICIÓN PARA DETERMINAR LA CONTAMINACIÓN AMBIENTAL POR METALES PESADOS: DE LAS MOLÉCULAS A LOS ECOSISTEMAS

  2013cites this paper
• Facilitated bioaccumulation of cadmium and copper in the oyster Crassostrea hongkongensis solely exposed to zinc.

  2013cites this paper
• BIOMARKERS OF EXPOSURE FOR ASSESSING ENVIRONMENTAL METAL POLLUTION: FROM MOLECULES TO ECOSYSTEMS

  2013cites this paper
• Metallothionein-like proteins induced by cadmium stress in the scallop Mizuhopecten yessoensis

  2012cites this paper
• Evolution of copper tolerance in yeast cells

  2012cites this paper
• Biochemical Characterization of Theromin, a Novel Leech Inhibitor, and the Interaction between the Fourth Metalbinding Domain of Wilson Disease Protein and Its Copper(I) Chaperone HAH1

  2010influential citation
• A perspective on global spread of dreissena polymorpha: A review on possibilities and limitations

  2010cites this paper
• The zebra mussel in Europe

  2010cites this paper
• Determinations of Uranium(VI) Binding Properties with some Metalloproteins (Transferrin, Albumin, Metallothionein and Ferritin) by Fluorescence Quenching

  2010cites this paper
• Chapter 29. Zinc

  2008cites this paper
• The subcellular fate of cadmium and zinc in the scallop Chlamys nobilis during waterborne and dietary metal exposure.

  2008cites this paper
• Pasture soils contaminated with fertilizer-derived cadmium and fluorine: livestock effects.

  2008cites this paper
• Peptide Folding, Metal-Binding Mechanisms, and Binding Site Structures in Metallothioneins

  2006cites this paper
• Oxidative stress in "Saccharomyces cerevisiae" : The Key role of Isc1p sphingomyelinase in cell resistance, and the molecular mechanisms associated to the recovery from hidrogen peroxide stress

  2004cites this paper
• Cu+ distribution in metallothionein fragments.

  2004cites this paper
• Divalent Metal Transporter 1 in Lead and Cadmium Transport

  2004cites this paper
• Model reactions of Cr (VI) with DNA mediated by thiol species

  2004cites this paper
• Lead-induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma (HepG2) cells

  2004cites this paper
• Recycling of sewage sludge to grassland: a review of the legislation to control of the localization and accumulation of potential toxic metals in grazing systems

  2003cites this paper
• Apoptosis by Cd2+ or CdMT in proximal tubule cells: different uptake routes and permissive role of endo/lysosomal CdMT uptake.

  2003cites this paper
• Fertiliser contaminants in New Zealand grazed pasture with special reference to cadmium and fluorine — a review

  2003cites this paper
• Recent developments in quantification methods for metallothionein.

  2002cites this paper
• Model reactions of Cr (VI) with DNA mediated by thiol species.

  2001cites this paper
• Accumulation of potentially toxic elements in the body tissues of sheep grazed on grassland given repeated applications of sewage sludge

  2001cites this paper
• Molecular mechanisms of metal toxicity and carcinogenesis

  2001cites this paper
• Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma cells (HepG2) exposed to cadmium chloride

  2001cites this paper
• Metallothionein-null mice are more sensitive than wild-type mice to liver injury induced by repeated exposure to cadmium.

  2000cites this paper
• Metallothionein: an intracellular protein to protect against cadmium toxicity.

  1999cites this paper
• Sublethal parameters in morphologically deformed Chironomus larvae: clues to understanding their bioindicator value

  1998cites this paper
• Chapter 30 – Developmental Neurotoxicity of Cadmium

  1998cites this paper
• Developmental Neurotoxicity of Cadmium

  1998cites this paper
• Susceptibility of MT-null mice to chronic CdCl2-induced nephrotoxicity indicates that renal injury is not mediated by the CdMT complex.

  1998cites this paper
• Experimental Factors That May Affect Toxicity of Cadmium to Freshwater Organisms

  1997cites this paper
• Copper ions and the regulation ofSaccharomyces cerevisiae metallothionein genes under aerobic and anaerobic conditions

  1996cites this paper
• Enhanced Effectiveness of Copper Ion Buffering by CUP1 Metallothionein Compared with CRS5 Metallothionein in Saccharomyces cerevisiae*

  1996cites this paper
• Experimental factors that may affect toxicity of aqueous and sediment-bound copper to freshwater organisms

  1996cites this paper
• TOXICITY AND INTAKES OF VARIOUS FORMS OF HEAVY METALS

  1996cites this paper
• Quantitation of Metallothionein

  1996cites this paper
• Metabolic changes of cadmium and zinc in kidney and liver tissue during foetal development in Romney and Merino sheep

  1995cites this paper
• Embryo-larval tolerance of Mytilus galloprovincialis, exposed to elevated seawater metal concentrations—II. Stage-specific fluctuations in sensitivity toward Zn and Cd and their bioaccumulation into veliger larvae

  1994cites this paper
• Effects of copper on rat hepatoma HTC cells and primary cultured rat hepatocytes.

  1994cites this paper
• Effects of copper on rat hepatoma HTC cells and primary cultured rat hepatocytes.

  1994cites this paper
• Role of cytosolic copper, metallothionein and glutathione in copper toxicity in rat hepatoma tissue culture cells.

  1994cites this paper
• Literature Review Report: Possible Means of Evaluating the Biological Effects of Sub-Aqueous Disposal of Mine Tailings.

  1993cites this paper
• Determination of zinc-65, copper-64 and sulphur-35 labelled rat hepatoma tissue culture metallothioneins by high-performance liquid chromatography with on-line radioactivity detection.

  1993cites this paper
• Distribution of 64Cu in Saccharomyces cerevisiae: cellular locale and metabolism.

  1993cites this paper
• Effects of cadmium, copper and metallothionein synthesis inhibiting and stimulating compounds on zinc uptake and accumulation in rat hepatoma HTC cells.

  1992cites this paper
• Effects of chelating agents on the cadmium burden of cells in culture

  1991cites this paper
• Sex differences in hepatic and renal cadmium accumulation and metallothionein induction. Role of estradiol.

  1991cites this paper
• Histological features, DNA content and prognosis of breast carcinoma found incidentally or in screening.

  1991cites this paper
• Metallothioneins and detoxification. Is the use of detoxication protein for mts a language abuse?

  1991cites this paper
• Isolation and partial characterization of cadmium-induced metallothionein-like proteins in Mytilus galloprovincialis

  1991cites this paper
• Implications of heavy metal toxicity related to EDTA exposure

  1990cites this paper
• Metallothionein and other cadmium-binding proteins: recent developments.

  1990cites this paper
• A comparison of cadmium-induced metallothionein gene expression and Me2+ distribution in the tissues of cadmiumsensitive (rainbow trout; Salmo gairdneri) and tolerant (stone loach; Noemacheilus barbatulus) species of freshwater fish

  1990cites this paper
• New aspects on the distribution and metabolism of essential trace elements after dietary exposure to toxic metals

  1989cites this paper
• Characterization and development of metallothionein in fetal forelimbs, brain and liver from the mouse.

  1989cites this paper
• Kinetic analysis of cadmium binding to metallothionein and other intracellular ligands in oyster gills

  1989cites this paper
• Metallothionein and Metallothionein-Like Proteins: Physiological Importance

  1989cites this paper
• Mechanistic aspects of the dithiocarbamate-induced mobilization of cadmium.

  1989cites this paper
• Structure—Reactivity Relationships of Metallothionein, a Unique Metal-Binding Protein

  1989cites this paper
• Copper histochemistry of 5 murine tumors and their respective metastases.

  1989cites this paper
• Cadmium-induced metallothionein in earthworms (Lumbricus terrestris)

  1989cites this paper
• Resistance of temperature tolerance ability of green sunfish to cadmium exposure

  1988cites this paper
• Metallothionein synthesis and its induction mechanism: Correlation with metal ion electronic configurations and softness parameters

  1988cites this paper
• Ultrastructural and biochemical studies of intracellular metal-binding patterns in kidney tubule cells of the scallop Placopecten magellanicus following prolonged exposure to cadmium or copper

  1988cites this paper
• Presence of Zn,Cu-binding protein in liver of freshwater fishes in the absence of elevated exogenous metal: Relevance to toxic metal exposure

  1988cites this paper
• Age-dependent variation for inducibility of metallothionein genes in mouse liver by cadmium.

  1988cites this paper
• Cadmium and zinc interactions in fish: Effects of zinc on the uptake, organ distribution, and elimination of109Cd in the zebrafish,Brachydanio rerio

  1988cites this paper
• METAL REGULATION AND MOLTING IN THE BLUE CRAB, CALLINECTES SAPIDUS: METALLOTHIONEIN FUNCTION IN METAL METABOLISM.

  1987cites this paper
• Detection of cadmium-binding proteins in fish chronically exposed to heavy metals

  1987cites this paper
• Intracellular compartmentation of metals in aquatic organisms: roles in mechanisms of cell injury.

  1987cites this paper
• METAL REGULATION AND MOLTING IN THE BLUE CRAB, CALLINECTES SAPIDUS: METALLOTHIONEIN FUNCTION

  1987cites this paper