Cysteine & Metals or Toxic Metals

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Toxic Metals Data

Life Flow One
The Solution For Heart Disease

by
Karl Loren

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Click On The Number To View The Study
Number	Title or Description	Comment
First Section #1 through #15	Search Parameters Were: Results for your query: Search all fields for: cysteine And toxic metal Published in 1977 through 1999 Only select references with abstracts available Show references published in English only Show references pertaining to humans Documents: 1 to 15 of 15
...1...	Cysteine metabolism and metal toxicity.
...2...	Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures.
...3...	Role of sulfhydryls in the hepatotoxicity of organic and metallic compounds.
...4...	CPx-type ATPases: a class of P-type ATPases that pump heavy metals [see comments]
...5...	Metallothionein induction in human peripheral blood lymphocytes by heavy metals.
...6...	Cysteine protects Na,K-ATPase and isolated human lymphocytes from silver toxicity.
...7...	A novel approach for heavy metal poisoning treatment, a model. Mercury poisoning by means of chelating microspheres: hemoperfusion and oral administration.
...8...	Effect of ascorbic, isoascorbic and dehydroascorbic acids on the growth and survival of Campylobacter jejuni.
...9...	Hepatic metallothionein as a source of zinc and cysteine during the first year of life.
...10...	Regulation of metallothionein gene expression.
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...11...	Cobalt in the environment and its toxicological implications.
...12...	Flow cytometric determination of metallothionein levels in human peripheral blood lymphocytes: utility in environmental exposure assessment.
...13...	Involvement of metallothionein and copper in cell proliferation.
...14...	Analysis of mammalian metallothionein isoforms by high-resolution SDS-gel electrophoresis.
...15...	Regulation of metallothionein production in HeLa cells.
The Reports Above Were Found with a search phrase which included: Cysteine and "toxic metal" The Reports Below Were Found with a search phrase which included: Cysteine and metal
Second Section	Search Parameters Were: Results for your query: Search all fields for: cysteine And metal Published in 1977 through 1999 Only select references with abstracts available Show references published in English only Show references pertaining to humans Documents: 1 to 100 of 248
...A1...	Factor IX Zutphen: a Cys18-->Arg mutation results in formation of a heterodimer with alpha 1-microglobulin and the inability to form a calcium-induced conformation.
...A2...	Thiol groups and reduced acidogenicity of dental plaque in the presence of metal ions in vivo.
...A3...	Antibody constant region: potential to bind metal and nucleic acid.
...A4...	Dimerization of the human papillomavirus E7 oncoprotein in vivo.
...A5...	Cysteine metabolism and metal toxicity.
...A6...	NMR analysis of the structure and metal sequestering properties of metallothioneins.
...A7...	Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures.
...A8...	Affinity cleavage at the metal-binding site of phosphoenolpyruvate carboxykinase.
...A9...	Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase [see comments]
...A10...	Role of sulfhydryls in the hepatotoxicity of organic and metallic compounds.
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...A11...	Selective inactivation of butyrylcholinesterase with metal chelators suggests there is more than one metal binding site.
...A12...	Reversal of heavy metal resistance in multidrug-resistant human KB carcinoma cells.
...A13...	Patients with homocystinuria: high metal concentrations in hair, blood and urine.
...A14...	Purification of glycogen phosphorylase isozymes by metal-affinity chromatography.
...A15...	A structural role for metal ions in the "wild-type" conformation of the tumor suppressor protein p53.
...A16...	Immobilized metal ion affinity chromatography of serum albumins.
...A17...	Metallothionein: an exceptional metal thiolate protein.
...A18...	Combined deficiency of xanthine oxidase and sulphite oxidase: a defect of molybdenum metabolism or transport?
...A19...	An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding.
...A20...	Structure of mammalian metallothionein.
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...A21...	NMR analysis of the structure and metal sequestering properties of metallothioneins.
...A22...	Glutathione mercaptides as transport forms of metals.
...A23...	Induction of metallothionein mRNA in HeLa cells by dexamethasone and by heavy metals.
...A24...	Functional domains of the heavy metal-responsive transcription regulator MTF-1.
...A25...	Interaction of mammalian sperm nuclear protamines and peptides derived thereof with immobilized zinc.
...A26...	Memories of metallothionein.
...A27...	Catalase inactivation following photosensitization with tetrasulfonated metallophthalocyanines.
...A28...	113Cd nmr study of the metal cluster structure of human liver metallothionein.
...A29...	Features of structural zinc in mammalian alcohol dehydrogenase. Site-directed mutagenesis of the zinc ligands.
...A30...	The metal ion requirement for activation of latent collagenase from human polymorphonuclear leucocytes.
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...A31...	A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor.
...A32...	Characterization of interactions of nitric oxide with human hemoglobin A by infrared spectroscopy.
...A33...	Mutation of the metal-bridging proton-donor His63 residue in human Cu, Zn superoxide dismutase. Biochemical and biophysical analysis of the His63-->Cys mutant.
...A34...	Proteolytic processing of Alzheimer's disease beta A4 amyloid precursor protein in human platelets.
...A35...	EEA1, an early endosome-associated protein. EEA1 is a conserved alpha-helical peripheral membrane protein flanked by cysteine "fingers" and contains a calmodulin-binding IQ motif.
...A36...	Solution structure of a cysteine rich domain of rat protein kinase C.
...A37...	Metal binding 'finger' structures in the glucocorticoid receptor defined by site-directed mutagenesis.
...A38...	Heavy metal inhibition of carnitine acetyltransferase activity in human placental syncytiotrophoblast: possible site of action of HgCl2, CH3HgCl, and CdCl2.
...A39...	Histamine as a ligand in blood plasma. Part 6. Aspartate and glutamate as possible partner ligands for zinc and histamine to favour histamine catabolism.
...A40...	Exposure of hydrophobic moieties promotes the selective degradation of hydrogen peroxide-modified hemoglobin by the multicatalytic proteinase complex, proteasome.
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...A41...	Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene.
...A42...	Tumor-promoting phorbol esters and cell proliferation stimulate secretion of basement membrane (type IV) collagen-degrading metalloproteinase by human fibroblasts.
...A43...	Immobilized-enzyme rate-determination method for glucose analysis.
...A44...	Involvement of cysteine, serotonin and their analogues in peroxidase-oxidase reactions.
...A45...	Determination and metabolism of dithiol chelating agents. VI. Isolation and identification of the mixed disulfides of meso-2,3-dimercaptosuccinic acid with L-cysteine in human urine.
...A46...	Structural and functional characterization of human immunodeficiency virus tat protein.
...A47...	The extended environment of mononuclear metal centers in protein structures.
...A48...	Thermoanaerobacter brockii alcohol dehydrogenase: characterization of the active site metal and its ligand amino acids.
...A49...	Intersubunit fluorescence energy transfer in human factor VIII.
...A50...	Quantitative investigation of copper(II) and zinc(II) complexes with S-carboxymethyl-L-cysteine and computer-simulated appraisal of their potential significance in vivo.
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...A51...	Distinct metal-thiolate clusters in the N-terminal domain of neuronal growth inhibitory factor.
...A52...	The effects of heavy metal cations and sulfhydryl reagents on degranulation from digitonin-permeabilized neutrophils.
...A53...	Protein carbonyl formation in blood plasma by cephalosporins.
...A54...	Effects of sulfhydryl regents on the activity of lambda Ser/Thr phosphoprotein phosphatase and inhibition of the enzyme by zinc ion.
...A55...	A novel MT gene of rice plants is strongly expressed in the node portion of the stem.
...A56...	Purification and characterization of a protease from Bacteroides gingivalis 381.
...A57...	Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II).
...A58...	CPx-type ATPases: a class of P-type ATPases that pump heavy metals [see comments]
...A59...	A mutant metallothionein which has inverse fragment composition exhibits high cadmium-binding ability.
...A60...	Structure of the rainbow trout metallothionein B gene and characterization of its metal-responsive region.
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...A61...	Structure and tissue-specific expression of the human metallothionein IB gene.
...A62...	Functional constituents of the active site of human neutrophil collagenase.
...A63...	Engineering a cysteine ligand into the zinc binding site of human carbonic anhydrase II.
...A64...	N-terminal domains of human copper-transporting adenosine triphosphatases (the Wilson's and Menkes disease proteins) bind copper selectively in vivo and in vitro with stoichiometry of one copper per metal-binding repeat.
...A65...	Heteronuclear 113Cd-1H NMR study of metal coordination in the human retinoic acid receptor-beta DNA binding domain.
...A66...	Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-kappaB activation.
..A67...	Physicochemical properties of charge isomers of recombinant human superoxide dismutase.
...A68...	A comparison of cysteine and serine proteinases in human gingival crevicular fluid with tissue, saliva and bacterial enzymes by analytical isoelectric focusing.
...A69...	Characterization of zinc-binding sites in human stromelysin-1: stoichiometry of the catalytic domain and identification of a cysteine ligand in the proenzyme.
...A70...	Induction of drug resistance to gold sodium thiomalate in a monocyte cell line, THP-1.
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...A71...	Oxidation of low density lipoprotein by thiols: superoxide-dependent and -independent mechanisms.
...A72...	Alterations of thiol metabolism in human cell lines induced by low amounts of copper, mercury or cadmium ions.
...A73...	Identification and functional requirement of Cu(I) and its ligands within coagulation factor VIII.
...A74...	Metallothionein induction in human peripheral blood lymphocytes by heavy metals.
...A75...	Metal binding properties and secondary structure of the zinc-binding domain of Nup475.
...A76...	Metal binding properties and secondary structure of the zinc-binding domain of Nup475.
...A77...	Cloning and nucleotide sequence of a complementary DNA encoding Xenopus laevis metallothionein: mRNA accumulation in response to heavy metals.
...A78...	The peptidase activity of human serum butyrylcholinesterase: studies using monoclonal antibodies and characterization of the peptidase.
...A79...	Disruption of prosomes by some bivalent metal ions results in the loss of their multicatalytic proteinase activity and cancels the nuclease resistance of prosomal RNA.
...A80...	Transient induction of the MRP/GS-X pump and gamma-glutamylcysteine synthetase by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea in human glioma cells.
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...A81...	Complexation of copper(I) by thioamino acids. Implications for copper speciation in blood plasma.
...A82...	Human papillomavirus type 16 E6 proteins with glycine substitution for cysteine in the metal-binding motif.
...A83...	Monoclonal antibodies specific for Semliki Forest virus replicase protein nsP2.
...A84...	Determination and metabolism of dithiol chelating agents. XVII. In humans, sodium 2,3-dimercapto-1-propanesulfonate is bound to plasma albumin via mixed disulfide formation and is found in the urine as cyclic polymeric disulfides.
...A85...	Physiological thiol compounds exert pro- and anti-oxidant effects, respectively, on iron- and copper-dependent oxidation of human low-density lipoprotein.
...A86...	Human placenta cytidine deaminase: a zinc metalloprotein.
...A87...	In vitro study of the NS2-3 protease of hepatitis C virus.
...A88...	Sequence analysis of P gene of human parainfluenza type 2 virus: P and cysteine-rich proteins are translated by two mRNAs that differ by two nontemplated G residues.
...A89...	Cysteine protects Na,K-ATPase and isolated human lymphocytes from silver toxicity.
...A90...	The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle stabilized by zinc.
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...A91...	The cysteine-rich domain of human proteins, neuronal chimaerin, protein kinase C and diacylglycerol kinase binds zinc. Evidence for the involvement of a zinc-dependent structure in phorbol ester binding.
...A92...	Cysteine mapping in the ion selectivity and toxin binding region of the cardiac Na+ channel pore [published erratum appears in J Membr Biol 1997 Mar 1;156(1):98]
...A93...	The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I) [see comments]
...A94...	Identification of an ATPase activity associated with a 71-kilodalton polypeptide encoded in gene 1 of the human coronavirus 229E.
...A95...	The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties.
...A96...	Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase.
...A97...	Metal ion and salt effects on the phospholipase A2, lysophospholipase, and transacylase activities of human cytosolic phospholipase A2.
...A98...	The mechanism of Hg2+ toxicity in cultured human oral fibroblasts: the involvement of cellular thiols.
...A99...	Maleimidocysteineamido-DOTA derivatives: new reagents for radiometal chelate conjugation to antibody sulfhydryl groups undergo pH-dependent cleavage reactions.
...A100...	Role of oxygen and metal ions in the instability of streptolysin O.

HealthGate Documents

Record 1 from database: MEDLINE
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Title: Cysteine metabolism and metal toxicity.
Author: Quig D
Address: Doctor's Data, Inc., West Chicago, IL, USA. dquig@doctorsdata.com
Source: Altern Med Rev, 1998 Aug, 3:4, 262-70
Abstract: Chronic, low level exposure to toxic metals is an increasing global problem. The symptoms associated with the slow accumulation of toxic metals are multiple and rather nondescript, and overt expression of toxic effects may not appear until later in life. The sulfhydryl-reactive metals (mercury, cadmium, lead, arsenic) are particularly insidious and can affect a vast array of biochemical and nutritional processes. The primary mechanisms by which the sulfhydryl-reactive metals elicit their toxic effects are summarized. The pro-oxidative effects of the metals are compounded by the fact that the metals also inhibit antioxidative enzymes and deplete intracellular glutathione. The metals also have the potential to disrupt the metabolism and biological activities of many proteins due to their high affinity for free sulfhydryl groups. Cysteine has a pivotal role in inducible, endogenous detoxication mechanisms in the body, and metal exposure taxes cysteine status. The protective effects of glutathione and the metallothioneins are discussed in detail. Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function. Metal exposure also affects essential element status, which can further decrease antioxidation and detoxification processes. Early detection and treatment of metal burden is important for successful detoxification, and optimization of nutritional status is paramount to the prevention and treatment of metal toxicity.
Language of Publication: English
Unique Identifier: 98404750

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MeSH Heading (Major): Arsenic|ME/*PO; Cysteine|DE/*ME; Metals, Heavy|ME/*PO
MeSH Heading: Chronic Disease; Endocrine Glands|DE; Human; Leucine|ME; Mercury|ME; Mercury Poisoning|ME/TH; Oxidation-Reduction|DE; Poisoning|TH

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 1089-5159
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Metals, Heavy); 4371-52-2 (Cysteine); 7005-03-0 (Leucine); 7439-97-6 (Mercury); 7440-38-2 (Arsenic)

Record 2 from database: MEDLINE
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Title: Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures.
Author: Hultberg B; Andersson A; Isaksson A
Address: Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Source: Toxicology, 1997 Feb, 117:2-3, 89-97
Abstract: Ions of metals such as copper, mercury, silver and cadmium are known to exhibit a high affinity for thiol groups and may therefore severely disturb many metabolic functions in the cell. Copper ions are also known to catalyse the formation of toxic oxygen species through a series of redox reactions. In the present study, we have determined the concentration of reduced and total glutathione, cysteine and homocysteine in a cell culture system (HeLa cell line) after addition of these metal ions. The main findings of the metal ion effect on the total thiol concentrations are that all metal ions increased the release of glutathione into the medium. Since the intracellular concentration of glutathione did not decrease under these conditions, the synthesis of glutathione must have been increased. In contrast to the other metal ions, copper ions also increased the release of homocysteine into the medium, possibly through interaction with S-adenosylhomocysteine hydrolase. The main findings of metal ion effects on reduced thiol are that, at concentrations not interfering with cell growth, mercury, silver and cadmium ions increased the concentration of extracellular reduced glutathione, possibly reflecting the increase of total glutathione in the medium. In contrast to the other metal ions, the addition of even very low amounts of copper ions (1 mumol/l) decreased the concentration of intra- and extracellular reduced thiols indicating oxidative stress.
Language of Publication: English
Unique Identifier: 97210824

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MeSH Heading (Major): Copper|*TO; Cysteine|*DE/ME; Glutathione|BI/*DE; Hela Cells|*DE/ME; Homocysteine|*DE/ME; Metals, Heavy|*TO
MeSH Heading: Animal; Cadmium|TO; Cations|TO; Human; Mercury|TO; Oxidation-Reduction; Oxidative Stress|DE; Silver|TO; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE
ISSN: 0300-483X
Country of Publication: IRELAND

Record 3 from database: MEDLINE
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Title: Role of sulfhydryls in the hepatotoxicity of organic and metallic compounds.
Author: Klaassen CD; Bracken WM; Dudley RE; Goering PL; Hazelton GA; Hjelle JJ
Address
Source: Fundam Appl Toxicol, 1985 Oct, 5:5, 806-15
Abstract: Endogenous sulfhydryl compounds serve a critical role in maintaining the function and viability of living systems. Glutathione (GSH) is the most abundant of these nonprotein thiols. During the past decade it has been demonstrated that sulfhydryls such as GSH also serve an important role in protecting vital nucleophilic sites in the liver from electrophilic attack by numerous classes of reactive chemicals. Organocompounds such as bromobenzene and acetaminophen which undergo microsomal metabolism yield reactive intermediates that are specifically inactivated by conjugation with sulfhydryls in the form of GSH. Thus, for organocompounds GSH is extremely important in protecting against toxic insults. More recently, other sulfhydryl compounds also have been found to serve a specific but as yet less defined role in protecting biological systems against chemically induced injury. Metals such as cadmium have a high affinity for sulfhydryls and the metal binding protein metallothionein binds cadmium with high affinity. The highly specific association of the metal with this sulfhydryl-enriched protein serves to effectively sequester the reactive cadmium ion. The central role of sulfhydryl equivalents in the detoxication of organo- and metallocompounds is similar; however, the mechanism by which this is achieved is fundamentally different.
Language of Publication: English
Unique Identifier: 86056693

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MeSH Heading (Major): Hepatitis, Toxic|*ME; Metals|*TO; Sulfhydryl Compounds|*ME
MeSH Heading: Acetaminophen|TO; Animal; Biotransformation; Bromobenzenes|TO; Cadmium Poisoning|ME; Cysteine|PD; Cytochrome P-450|ME; Human; Metallothionein|ME; Microsomes, Liver|EN; Support, U.S. Gov't, P.H.S.; Zinc|TO

Publication Type: JOURNAL ARTICLE
ISSN: 0272-0590
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Bromobenzenes); 0 (Metals); 0 (Sulfhydryl Compounds); 103-90-2 (Acetaminophen); 4371-52-2 (Cysteine); 7440-66-6 (Zinc); 9035-51-2 (Cytochrome P-450); 9038-94-2 (Metallothionein)

Record 4 from database: MEDLINE
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Title: CPx-type ATPases: a class of P-type ATPases that pump heavy metals [see comments]
Author: Solioz M; Vulpe C
Address: Department of Clinical Pharmacology, University of Berne, Switzerland. solioz@ikp.unibe.ch
Source: Trends Biochem Sci, 1996 Jul, 21:7, 237-41
Abstract: ATP-driven heavy metal pumps represent a newly defined class of proteins that translocate toxic and essential metals across biological membranes. These transporters form a separate evolutionary branch of the ion-transporting P-type ATPases. We propose to call these enzymes CPx-type ATPases, based on the common novel feature of a conserved intramembranous cysteine-proline-cysteine or cysteine-proline-histidine motif.
Language of Publication: English
Unique Identifier: 96334292

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MeSH Heading (Major): Adenosinetriphosphatase|CH/*ME; Conserved Sequence|*; Ion Pumps|*ME; Metals|*ME
MeSH Heading: Amino Acid Sequence; Human; Molecular Sequence Data; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE
ISSN: 0167-7640
Country of Publication: ENGLAND

Record 5 from database: MEDLINE
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Title: Metallothionein induction in human peripheral blood lymphocytes by heavy metals.
Author: Yamada H; Koizumi S
Address: Department of Experimental Toxicology, National Institute of Industrial Health, Kawasaki, Japan.
Source: Chem Biol Interact, 1991, 78:3, 347-54
Abstract: Human peripheral blood lymphocytes have the capacity to produce metallothioneins (MTs) as a protective response to cadmium exposure. To define the range of metal species inducing lymphocyte MTs, cellular proteins synthesized after exposure to each of 11 heavy metals were analyzed by gel electrophoresis. Toxic metals such as cadmium, mercury and silver were found to induce thioneins (apoproteins of MTs) at relatively low concentrations (maximum at approximately 10 microM), whereas less toxic metals such as zinc, copper and nickel were inductive at relatively high concentrations (maximum at approximately 200 microM). Tin, lead, iron, cobalt, and manganese did not induce thioneins. The heavy metal specificity of MT induction in the lymphocyte resembles that in the liver, and the regulatory mechanism of MT production seems to be similar in both of these tissues. In the cells exposed to highly toxic metals such as cadmium and mercury, expression of cytotoxicity (represented by decline of cysteine uptake) was remarkable at the metal concentrations higher than those saturating thionein induction, supporting the protective role of MTs against heavy metals.
Language of Publication: English
Unique Identifier: 91300580

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MeSH Heading (Major): Lymphocytes|DE/*ME; Metallothionein|*BI; Metals|*TO
MeSH Heading: Electrophoresis, Polyacrylamide Gel; Human; Male

Publication Type: JOURNAL ARTICLE
ISSN: 0009-2797
Country of Publication: NETHERLANDS
CAS Registry/EC Number: 0 (Metals); 9038-94-2 (Metallothionein)

Record 6 from database: MEDLINE
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Title: Cysteine protects Na,K-ATPase and isolated human lymphocytes from silver toxicity.
Author: Hussain S; Anner RM; Anner BM
Address: Laboratory of Experimental Therapeutics, Geneva University Medical Center, Switzerland.
Source: Biochem Biophys Res Commun, 1992 Dec 30, 189:3, 1444-9
Abstract: Metal-binding proteins are important components of retroviruses such as human immunodeficiency virus (HIV). Therefore, metals could be used as antiviral agents. However, most metals are toxic for humans with the exception of silver which is toxic only to prokaryotic cells and viruses. In addition, HIV infection causes a decrease in body cysteine. We formed a complex of silver and cysteine, named silver-cysteine. Healthy human lymphocytes were incubated with silver-nitrate or silver-cysteine. Negligible cell survival was seen at 50 microM silver-nitrate. However, in presence of 1 mM cysteine, the viability remained unaffected up to 1 mM of silver. Further, silver inhibition of isolated Na,K-ATPase was easily reversed by cysteine. Thus, non-toxic silver-cysteine could be used as an anti-viral and cysteine-replenishing agent.
Language of Publication: English
Unique Identifier: 93129209

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MeSH Heading (Major): Cysteine|*PD; Lymphocytes|CY/*DE; Na(+)-K(+)-Exchanging ATPase|AI/*ME; Silver|*TO
MeSH Heading: Animal; Cell Survival|DE; Human; HIV|DE; In Vitro; Kidney Medulla|EN; Kinetics; Sheep; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE
ISSN: 0006-291X
Country of Publication: UNITED STATES
CAS Registry/EC Number: EC 3.6.1.37 (Na(+)-K(+)-Exchanging ATPase); 4371-52-2 (Cysteine); 7440-22-4 (Silver)

Record 7 from database: MEDLINE
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Title: A novel approach for heavy metal poisoning treatment, a model. Mercury poisoning by means of chelating microspheres: hemoperfusion and oral administration.
Author: Margel S
Address
Source: J Med Chem, 1981 Oct, 24:10, 1263-6
Abstract: The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poisoning is under investigation in our group. The approach utilizes the synthesis of chelating microspheres specific for the desired metallic compound. The microspheres are suggested for use in severe cases by means of hemoperfusion, as a first aid, and then by oral administration. As a model this approach was tried for mercury poisoning. Polymercaptal microspheres of 0.8 micrometer average size were synthesized. The microspheres have a high surface area, have a high affinity toward organic and inorganic mercury compounds, and can compete easily with albumin and cysteine in the ability to bind mercury compounds. These microspheres also were encapsulated with agarose--a blood compatible polymer--and were tried successfully for plasma perfusion (in 10 min, 40% of CH3HgCl and of HgCl2 were removed from 20 ppm of poisoned plasma).
Language of Publication: English
Unique Identifier: 82122390

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MeSH Heading (Major): Chelating Agents|*AD/ME; Hemoperfusion|*; Mercury Poisoning|*TH
MeSH Heading: Administration, Oral; Human; Mercury|ME; Microspheres; Models, Biological

Publication Type: JOURNAL ARTICLE
ISSN: 0022-2623
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Chelating Agents); 7439-97-6 (Mercury)

Record 8 from database: MEDLINE
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Title: Effect of ascorbic, isoascorbic and dehydroascorbic acids on the growth and survival of Campylobacter jejuni.
Author: Juven BJ; Kanner J
Address
Source: J Appl Bacteriol, 1986 Oct, 61:4, 339-45
Abstract: Ascorbic acid (AsA), added to nutrient broth at a concentration of 5 mmol/l, was bactericidal towards Campylobacter jejuni grown at 42 degrees C in a micro-aerobic atmosphere. Specific enzymes, radical scavengers, metal chelators and reducing agents were tested as possible antagonists to the cytotoxicity of AsA. The addition of catalase or of the metal chelators ceruloplasmin or Desferal did not prevent the cytotoxic effect of AsA. The addition of the hydroxyl radical scavengers mannitol, formate, histidine or DMSO also failed to counteract the toxicity of AsA. On the other hand, thiourea or cysteamine and the reducing agents cysteine or dithionite significantly increased the recovery of C. jejuni in the presence of AsA. Although the possibility of the involvement of hydroxyl radicals in AsA cytotoxicity cannot be ruled out, it appears that the toxic effect of AsA is due mostly to the formation of products of oxidation of AsA and particularly to dehydroascorbic acid (DHA). Dehydroascorbic acid was also bactericidal to C. jejuni at a concentration of 5 mmol/l. Of all the compounds tested, only cysteamine was effective in preventing (partially) the toxic effect of DHA. The growth of C. jejuni was not inhibited by the addition of 5 mmol/l of isoascorbic acid or sodium isoascorbate.
Language of Publication: English
Unique Identifier: 87056716

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MeSH Heading (Major): Ascorbic Acid|*AA/*PD; Campylobacter fetus|DE/*GD; Dehydroascorbic Acid|*PD
MeSH Heading: Human; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.

Publication Type: JOURNAL ARTICLE
ISSN: 0021-8847
Country of Publication: ENGLAND
CAS Registry/EC Number: 490-83-5 (Dehydroascorbic Acid); 50-81-7 (Ascorbic Acid); 89-65-6 (isoascorbic acid)

Record 9 from database: MEDLINE
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Title: Hepatic metallothionein as a source of zinc and cysteine during the first year of life.
Author: Zlotkin SH; Cherian MG
Address: Department of Nutritional Sciences, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Source: Pediatr Res, 1988 Sep, 24:3, 326-9
Abstract: Metallothionein, a high cysteine-containing protein, can bind with both essential and nonessential metals and thus play an important role as a metal storage protein and also in the detoxification of toxic metals. Although in the human fetus, levels of trace minerals and metallothionein are very high, their postnatal changes are not well documented. The purpose of the present investigation, therefore, was to quantify the accumulation of metallothionein in premature and full-term infants during the first year of life and to identify factors affecting its accumulation. From 47 postmortem samples, it was determined that hepatic metallothionein levels were highest in newborn premature and full-term infants falling to levels found in older children by 4.4 months of age. Hepatic zinc levels were also highest in the youngest infants, falling with increasing postnatal age. There was a significant positive correlation between zinc and metallothionein at all ages. However, there was a negative correlation between hepatic metallothionein levels and cystathionase activity. Hepatic copper and metallothionein levels were unrelated. The renal concentration of metallothionein, zinc, and copper were significantly lower than corresponding hepatic levels. The fall in hepatic levels of zinc and metallothionein during the first months of life correspond to a period of negative zinc balance and low endogenous cysteine production in the newborn. Thus metallothionein may play an important role as a storage depot for these two essential nutrients during this critical period of active growth.
Language of Publication: English
Unique Identifier: 89098117

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MeSH Heading (Major): Infant, Newborn|*ME; Infant, Premature|*ME; Liver|GD/*ME; Metallothionein|*ME; Zinc|*ME
MeSH Heading: Aging; Copper|ME; Cystathionine gamma-Lyase|ME; Female; Human; Male; Reference Values

Publication Type: JOURNAL ARTICLE
ISSN: 0031-3998
Country of Publication: UNITED STATES
CAS Registry/EC Number: EC 4.4.1.1 (Cystathionine gamma-Lyase); 7440-50-8 (Copper); 7440-66-6 (Zinc); 9038-94-2 (Metallothionein)

Record 10 from database: MEDLINE
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Title: Regulation of metallothionein gene expression.
Author: Andrews GK
Address: Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66103.
Source: Prog Food Nutr Sci, 1990, 14:2-3, 193-258
Abstract: The metallothioneins are small, cysteine-rich proteins that have the capacity for high affinity binding of heavy metal ions, and whose synthesis is regulated by metal ion concentrations. These properties suggest that they play pivotal roles in the metabolism of the relatively nontoxic essential metals (zinc and copper), as well as toxic heavy metals (cadmium), a concept supported by a variety of studies of cells in culture, as well as in intact animals. Expression of the metallothionein genes may have important implications in the nutritional status of the animal, in its response to stresses (inflammation, heavy metal toxicity), and in embryonic, fetal and neonatal development. The complementary DNAs and genes that encode the metallothioneins have been cloned and analyzed from a wide variety of eukaryotes. Striking features of the metallothioneins include: their high degree of amino acid sequence similarity (including conservation in the placement of cysteine residues in the molecule reflecting their function in metal binding); a conserved tripartite gene structure; and their transcriptional induction by metal ions, as well as other hormonal and environmental stimuli. The precise mechanisms and biochemical pathways by which cells transduce environmental signals into transcriptional induction of the metallothionein genes are beginning to be defined. Recent studies indicate that metal effects are exerted via positive trans-acting factors induced to interact with cis-acting DNA sequences in the promoter, in turn leading to transcriptional induction. However, the metallothionein gene promoter is structurally complex, and contains binding sites for a variety of nuclear proteins that likely regulate basal as well as induced levels of expression of these genes. Recent studies also suggest the possible involvement of post-transcriptional processes in the regulation of metallothionein levels in the cell. Furthermore, evidence of striking differences in the levels of metallothionein gene expression among various cell types in vivo have recently been documented. Although several detailed reviews of the metallothioneins have been published recently, this review will focus, in large part, on the molecular biology of the metallothioneins, with particular emphasis on recent advances in our understanding of the mechanisms regulating expression of these interesting and important genes. Given the large volume of literature on the metallothioneins and the space limitations of this review, it is impossible to comprehensively cite the studies of each of my colleagues who have contributed so much to this field. Instead the reader is often directed to reviews of this subject for much of the earlier literature, and emphasis is placed on more current publications in this field.
Language of Publication: English
Unique Identifier: 91156807

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MeSH Heading (Major): Gene Expression Regulation|*; Metallothionein|CH/*GE
MeSH Heading: Amino Acid Sequence; Animal; Human; Molecular Sequence Data; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
ISSN: 0306-0632
Country of Publication: ENGLAND
CAS Registry/EC Number: 9038-94-2 (Metallothionein)

Record 11 from database: MEDLINE
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Title: Cobalt in the environment and its toxicological implications.
Author: Domingo JL
Address
Source: Rev Environ Contam Toxicol, 1989, 108:, 105-32
Abstract: Cobalt is an essential trace element which is widely distributed in nature. Most of cobalt consumed is used in the manufacture of alloys, and although not released extensively in the environment, it may represent a hazard to human health. In addition, excess dietary cobalt produces toxic effects in animals. Polycythemia and hyperglycemia with transitory damage to pancreatic alpha-cells have been widely reported after cobalt administration. Cobalt salts induce respiratory deficiency in yeast. CoCl2 increased sister chromatid exchange (SCE) in P388D1 cells and in lymphocytes from two donors. So far it has not been possible to induce cancer in experimental animals using cobalt by any other route than by injection. Ingestion of cobalt may lead to reproductive changes in the male rat such as loss of testicular volume and darkening of testicle color. On the other hand, oral administration of cobalt did not produce teratogenicity or significant fetotoxicity in the rat at daily doses as high as 100 mg CoCl2/kg. However, cobalt affected the period of late gestation as well as the postnatal development of the pups. Occupational toxicology of cobalt, hygienic and epidemiologic aspects, and treatment of cobalt poisoning are also topics of special interest. Cobalt is a metal with marked allergenic potential. Asthma, interstitial lung disease and combined asthma and alveolitis have been described as occupational health hazards. EDTA, DTPA, and N-acetyl-L-cysteine have been suggested as possible antidotes in cobalt intoxication.
Language of Publication: English
Unique Identifier: 89161229

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MeSH Heading (Major): Cobalt|PD/PK/*TO
MeSH Heading: Air Pollutants, Occupational|TO; Animal; Carcinogens; Chelating Agents|TU; Diet; Human; Lethal Dose 50; Mutagens; Rats; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0179-5953
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Air Pollutants, Occupational); 0 (Carcinogens); 0 (Chelating Agents); 0 (Mutagens); 7440-48-4 (Cobalt)

Record 12 from database: MEDLINE
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Title: Flow cytometric determination of metallothionein levels in human peripheral blood lymphocytes: utility in environmental exposure assessment.
Author: Yurkow EJ; Makhijani PR
Address: Department of Pharmacology and Toxicology, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08855-1179, USA. yurkow@rci.rutgers.edu
Source: J Toxicol Environ Health, 1998 Jul, 54:6, 445-57
Abstract: Metallothioneins (MT) are ubiquitous, low-molecular-weight proteins that exhibit high binding affinities for heavy metal ions. The expression of these cysteine-rich proteins is induced in response to various types of chemical and physical stresses and therefore can be used to assess human exposure to cytotoxic environmental agents. In the current study, MT levels of human peripheral blood lymphocytes were determined using an MT-specific antibody and flow cytometry. Treatment of human whole blood ex vivo with CdCl2 was found to induce a concentration- and time-dependent increase in lymphocyte MT levels at concentrations as low as 0.3 microM and within a 12-h period. Interestingly, differences were observed in the magnitude of cadmium-induced MT levels in the lymphocytes of six human test subjects. Two members of the study population exhibited CdCl2-induced cellular MT levels that were up to twofold greater than the lymphocytes of other human subjects. While the lymphocytes of most test subjects exhibited a symmetric (unimodal) distribution of cadmium-induced MT-specific fluorescence, the cells of two individuals displayed a heterogeneous (nonuniform) distribution of MT levels. Dual-parameter flow cytometric analysis using phenotype-specific antibodies indicated that variations in the responsiveness of subpopulations of lymphocytes to CdCl2 were responsible for the heterogeneous distribution of MT-specific cellular fluorescence. T-helper (CD4-positive) and T-suppressor/cytotoxic (CD8-positive) lymphocytes expressed higher cellular levels of MT than other lymphocyte subpopulations (i.e., B lymphocytes, natural killer cells). Our results suggest that MT protein levels of peripheral blood lymphocytes, as determined by this flow cytometric method, may be used to assess human exposure to toxic metals and to characterize various quantitative/qualitative aspects of the response of individuals to cadmium and possibly to other types of environmental stresses.
Language of Publication: English
Unique Identifier: 98324287

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MeSH Heading (Major): Environmental Exposure|*AN; Flow Cytometry|*MT; Leukocytes, Mononuclear|DE/*ME; Metallothionein|*BL
MeSH Heading: Adult; Biological Markers; Cadmium Chloride|TO; Cells, Cultured; Dose-Response Relationship, Drug; Female; Human; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE
ISSN: 0098-4108
Country of Publication: UNITED STATES

Record 13 from database: MEDLINE
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Title: Involvement of metallothionein and copper in cell proliferation.
Author: W…ostowski T
Address: Institute of Biology, Warsaw University, Bia…ystok, Poland.
Source: Biometals, 1993 Summer, 6:2, 71-6
Abstract: Metallothionein is a low-molecular weight, cysteine-rich, metal-binding protein which has been implicated in the detoxification of toxic metals (cadmium, mercury), metabolism of zinc and copper, as well as in the scavenging of free radicals. Recent evidence suggests that the protein may also be involved in cell proliferation. Based on the experiments carried out so far, it is assumed that the fundamental role of metallothionein in cell proliferation may be to detoxify and/or transfer copper ions from the cytoplasm to the nucleus at the G1/S phase, which in turn participate in some way in nuclear DNA synthesis.
Language of Publication: English
Unique Identifier: 93364161

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MeSH Heading (Major): Cell Division|*; Copper|*ME; Metallothionein|*ME
MeSH Heading: Amino Acid Sequence; Animal; Cell Cycle; Conserved Sequence; Evolution; Human

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0966-0844
Country of Publication: ENGLAND
CAS Registry/EC Number: 7440-50-8 (Copper); 9038-94-2 (Metallothionein)

Record 14 from database: MEDLINE
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Title: Analysis of mammalian metallothionein isoforms by high-resolution SDS-gel electrophoresis.
Author: Koizumi S; Otaki N; Saegusa J; Otsuka F
Address: Department of Experimental Toxicology, National Institute of Industrial Health, Kawasaki, Japan.
Source: Toxicol Lett, 1993 Feb, 66:2, 165-74
Abstract: Metallothioneins (MTs) are cysteine-rich heavy metal-binding proteins, whose possible functions are thought to be the protection against toxic metals as well as the regulation of essential metals. It is known that there are several MT isoforms, but the biological roles of the individual isoforms have not been elucidated. To facilitate the functional analysis of these isoforms, we improved an analytical method of MTs developed previously, which is based on a denaturing gel electrophoresis of chemically modified MTs. The established technique makes it possible not only to separate MT isoforms with a high resolution, but to estimate the levels of the individual isoforms by analyzing directly crude cell extracts. By this method, six MT isoforms were identified in the extracts of Cd-exposed human cells. It was also revealed that there is an apparent heterogeneity of the rat liver MT; five isoforms were identified in the liver extracts of Cd-injected rats. The present method will be useful in the functional analysis of the MT isoforms, as well as in a variety of aspects of the MT studies.
Language of Publication: English
Unique Identifier: 93158027

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MeSH Heading (Major): Metallothionein|*AN/CH/IP
MeSH Heading: Animal; Electrophoresis, Polyacrylamide Gel; Hela Cells; Human; Liver|CH; Male; Mice; Rats; Rats, Inbred Lew

Publication Type: JOURNAL ARTICLE
ISSN: 0378-4274
Country of Publication: NETHERLANDS
CAS Registry/EC Number: 9038-94-2 (Metallothionein)

Record 15 from database: MEDLINE
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Title: Regulation of metallothionein production in HeLa cells.
Author: Koizumi S; Sone T
Address: Department of Experimental Toxicology, National Institute of Industrial Health, Kawasaki, Japan.
Source: Toxicol Lett, 1991 Dec, 59:1-3, 73-80
Abstract: Metallothioneins are cysteine-rich, heavy-metal-binding proteins which have been assumed to participate in the detoxification of toxic metals. The mechanism of thionein (apoprotein of metallothionein) induction by cadmium was studied using cultured human cells. It was found that when thionein synthesis reaches a maximum (6-8 h after induction), it no longer responds to additional cadmium. Changes in cadmium uptake or induction of inhibitory proteins were not responsible. Together with our previous findings, a possible mechanism is proposed: loss of the secondary induction response might be due to increased intracellular levels of thionein, which has been overproduced by the initial induction.
Language of Publication: English
Unique Identifier: 92094614

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MeSH Heading (Major): Cadmium|ME/*TO; Metallothionein|*BI
MeSH Heading: Cells, Cultured; Cycloheximide|PD; Hela Cells|DE/ME; Human

Publication Type: JOURNAL ARTICLE
ISSN: 0378-4274
Country of Publication: NETHERLANDS
CAS Registry/EC Number: 66-81-9 (Cycloheximide); 7440-43-9 (Cadmium); 9038-94-2 (Metallothionein)

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(Not limited to "toxic metal"

Record A1 from database: MEDLINE
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Title: Factor IX Zutphen: a Cys18-->Arg mutation results in formation of a heterodimer with alpha 1-microglobulin and the inability to form a calcium-induced conformation.
Author: Wojcik EG; van den Berg M; van der Linden IK; Poort SR; Cupers R; Bertina RM
Address: Haemostasis and Thrombosis Research Centre, University Hospital, Leiden, The Netherlands.
Source: Biochem J, 1995 Nov, 311 ( Pt 3):, 753-9
Abstract: Factor IX Zutphen is a variant factor IX molecule isolated from the blood of a patient with severe haemophilia B. The molecular defect in factor IX Zutphen is a Cys18-->Arg mutation as a result of a T-->C transition at residue 6427 of the factor IX gene of the patient. The mutation disrupts the disulphide bond in the Gla-domain between Cys18 and Cys23. The remaining free cysteine residue results in the formation of a 95 kDa complex with alpha 1-microglobulin through an intermolecular disulphide bond. The same complex circulates at high levels in plasma of carriers of the mutation. The variant molecule has a calcium-binding defect, which is shown not to be caused by incomplete gamma-carboxylation. Factor IX Zutphen can not bind to phospholipids and can not be activated by factor XIa or by factor VIIa-tissue factor complex. Two sequential metal ion-dependent conformational transitions (factor IX-->factor IX'-->factor IX*) have been proposed for human factor IX [Liebman (1987) J. Biol. Chem. 262, 7605-7612], based upon the metal ion requirements for binding to anti-factor IX:Mg(II) antibodies, which are specific for the factor IX' conformation, and anti-factor IX:Ca(II) antibodies, which are specific for the factor IX* conformation. We used these conformation-specific antibodies, and antibodies raised against a synthetic peptide corresponding to residues 35-50 of human factor IX [anti-factor IX(35-50)] to study the metal ion-induced conformation of factor IX Zutphen. The disruption of the disulphide bond in the Gla-domain, maybe in combination with the complex with alpha 1-microglobulin, destabilized the factor IX' conformation. The formation of the factor IX* conformation was prevented independent of the presence of alpha 1-microglobulin. The disulphide bond in the Gla-domain is therefore essential for the calcium-dependent conformation and function of factor IX.
Language of Publication: English
Unique Identifier: 96067589

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MeSH Heading (Major): Alpha-Globulins|*ME; Calcium|*PD; Factor IX|CH/*GE/*ME; Mutation|*
MeSH Heading: Amino Acid Sequence; Antibody Specificity; Arginine|GE/ME; Cysteine|GE/ME; Human; Metals|PD; Molecular Sequence Data; Protein Binding; Protein Conformation; Structure-Activity Relationship; Support, Non-U.S. Gov't; 1-Carboxyglutamic Acid|AN

Publication Type: JOURNAL ARTICLE
ISSN: 0264-6021
Country of Publication: ENGLAND

Record A2 from database: MEDLINE
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Title: Thiol groups and reduced acidogenicity of dental plaque in the presence of metal ions in vivo.
Author: Oppermann RV; R‡lla G; Johansen JR; Assev S
Address
Source: Scand J Dent Res, 1980 Oct, 88:5, 389-96
Abstract: Metal ions are known to influence the cariogenicity of dental plaque. Inhibition of acid metabolism in plaque may be of importance in this respect. Metal ions inhibit the acidogenicity of dental plaque to a different extent and it has been suggested that an enzyme inhibition based on oxidation of thiol groups may explain this observation. The aim of the present study was to evaluate the significance of oxidation of thiol groups in the inhibition of acid production in plaque by silver, tin and zinc salts. Nine subjects with 3-d sucrose induced plaque received topical applications of the metal ions. Cysteine or glutathione, which are known to reverse thiol oxidations, were then applied in one side of the mouth. Plaque pH measurements, in the presence of sucrose, were performed prior to and up to 2 h after treatment. The results showed that the acid production inhibited by the metal ions was reactivated by cysteine or glutathione. Iodoacetamide and p-chloromercuribenzoate were also shown to inhibit acid formation in dental plaque. The high affinity silver, tin and zinc have for SH groups, the observed inhibitory effect of these metals, the reactivation of the metabolism by monothiols and the fact that organic sulfhydryl reagents inhibit acid formation in plaque indicate that oxidation of thiol groups may be the mechanism by which these metals exert their effect.
Language of Publication: English
Unique Identifier: 81126114

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MeSH Heading (Major): Cariogenic Agents|*; Dental Plaque|*ME; Metals|*PD; Sulfhydryl Compounds|*ME
MeSH Heading: Adult; Cysteine|PD; Glutathione|ME; Human; Hydrogen-Ion Concentration; Oxidation-Reduction; Silver|PD; Streptococcus mutans|GD; Tin|PD; Zinc|PD

Publication Type: JOURNAL ARTICLE
ISSN: 0029-845X
Country of Publication: DENMARK
CAS Registry/EC Number: 0 (Cariogenic Agents); 0 (Metals); 0 (Sulfhydryl Compounds); 4371-52-2 (Cysteine); 70-18-8 (Glutathione); 7440-22-4 (Silver); 7440-31-5 (Tin); 7440-66-6 (Zinc)

Record A3 from database: MEDLINE
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Title: Antibody constant region: potential to bind metal and nucleic acid.
Author: Radulescu RT
Address: Molecular Concepts Research (MCR), Munich, Germany.
Source: Med Hypotheses, 1995 Feb, 44:2, 139-45
Abstract: Environmental challenges appear to elicit similar patterns of cellular responses such as positive autoregulation and autoamplification whether one considers the generation of antibodies with identical antigen specificity or the accumulation of host-protective transcription factors. Therefore, I analyzed the structure of immunoglobulins (Ig) for motifs commonly found in transcription factors. Specifically, the well-known abundance and periodic location of cysteine residues in immunoglobulin chains prompted me to check antibody constant regions for the presence of putative metal-binding domains and zinc finger-like sequences. The constant regions of Ig light and heavy chains were found to harbor one or several copies, respectively, of a short cysteine- and histidine-containing sequence. Moreover, all four IgG subclasses were detected to comprise zinc finger-like motifs in their heavy chain constant and hinge domains. Yet another finding is the occurrence of several sequences of the form serine-proline-X-X and/or threonine-proline-X-X in the hinge sections of IgA and IgG3. These results suggest that antibody constant regions, as a fragment and/or embedded in a full-length immunoglobulin chain, may complex metal, thus acquiring conformations conducive to dimerization and nucleic acid binding. As such, my study provides a putative structural basis for the known requirement of divalent metal cations, particularly of zinc ions, for a normal immune response, and warrants further investigations, both theoretical and experimental, into the potential of antibody constant regions for metal binding and gene regulation. Moreover, future testing of the proposed zinc finger peptides from Ig constant domains should yield information relevant to zinc finger design with potentially wide applications in research and clinical medicine.(ABSTRACT TRUNCATED AT 250 WORDS)
Language of Publication: English
Unique Identifier: 95319353

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MeSH Heading (Major): DNA-Binding Proteins|*ME; Immunoglobulin Constant Region|CH/*ME; Metals|*ME; Models, Genetic|*; Models, Immunological|*; Zinc Fingers|*
MeSH Heading: Amino Acid Sequence; Cysteine; Evolution; Gene Expression Regulation; Human; Molecular Sequence Data; RNA, Viral|ME; Sequence Alignment; Signal Transduction; Transcription Factors|CH; Zinc|ME

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0306-9877
Country of Publication: ENGLAND

Record A4 from database: MEDLINE
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Title: Dimerization of the human papillomavirus E7 oncoprotein in vivo.
Author: Clemens KE; Brent R; Gyuris J; Münger K
Address: Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Source: Virology, 1995 Dec, 214:1, 289-93
Abstract: We have used a yeast two-hybrid system to show that human papillomavirus E7 proteins can form oligomeric complexes in vivo. The carboxyl-terminal cysteine-rich metal-binding domain is critical for this activity although amino-terminal sequences also contribute to oligomerization. Our experiments also reveal that E7 possesses an intrinsic transcription activation activity in yeast, which resides in the amino terminus of the protein.
Language of Publication: English
Unique Identifier: 96095252

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MeSH Heading (Major): Oncogene Proteins, Viral|*ME
MeSH Heading: Amino Acid Sequence; Binding Sites; Biopolymers; Cysteine|ME; Human; Metals|ME; Molecular Sequence Data; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Trans-Activation (Genetics); Yeasts

Publication Type: JOURNAL ARTICLE
ISSN: 0042-6822
Country of Publication: UNITED STATES

Record A5 from database: MEDLINE
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Title: Cysteine metabolism and metal toxicity.
Author: Quig D
Address: Doctor's Data, Inc., West Chicago, IL, USA. dquig@doctorsdata.com
Source: Altern Med Rev, 1998 Aug, 3:4, 262-70
Abstract: Chronic, low level exposure to toxic metals is an increasing global problem. The symptoms associated with the slow accumulation of toxic metals are multiple and rather nondescript, and overt expression of toxic effects may not appear until later in life. The sulfhydryl-reactive metals (mercury, cadmium, lead, arsenic) are particularly insidious and can affect a vast array of biochemical and nutritional processes. The primary mechanisms by which the sulfhydryl-reactive metals elicit their toxic effects are summarized. The pro-oxidative effects of the metals are compounded by the fact that the metals also inhibit antioxidative enzymes and deplete intracellular glutathione. The metals also have the potential to disrupt the metabolism and biological activities of many proteins due to their high affinity for free sulfhydryl groups. Cysteine has a pivotal role in inducible, endogenous detoxication mechanisms in the body, and metal exposure taxes cysteine status. The protective effects of glutathione and the metallothioneins are discussed in detail. Basic research pertaining to the transport of toxic metals into the brain is summarized, and a case is made for the use of hydrolyzed whey protein to support metal detoxification and neurological function. Metal exposure also affects essential element status, which can further decrease antioxidation and detoxification processes. Early detection and treatment of metal burden is important for successful detoxification, and optimization of nutritional status is paramount to the prevention and treatment of metal toxicity.
Language of Publication: English
Unique Identifier: 98404750

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MeSH Heading (Major): Arsenic|ME/*PO; Cysteine|DE/*ME; Metals, Heavy|ME/*PO
MeSH Heading: Chronic Disease; Endocrine Glands|DE; Human; Leucine|ME; Mercury|ME; Mercury Poisoning|ME/TH; Oxidation-Reduction|DE; Poisoning|TH

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 1089-5159
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Metals, Heavy); 4371-52-2 (Cysteine); 7005-03-0 (Leucine); 7439-97-6 (Mercury); 7440-38-2 (Arsenic)

Record A6 from database: MEDLINE
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Title: NMR analysis of the structure and metal sequestering properties of metallothioneins.
Author: Armitage IM; Dalgarno DC; Johnson BA
Address: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510.
Source: EXS, 1987, 52:, 159-69
Abstract: Multinuclear 1 and 2 dimensional magnetic resonance methods have been used to investigate the structures and metal binding properties of metallothioneins (MTs) isolated from several different sources. 113Cd NMR studies have unambiguously shown that the 7 g-atoms of Cd2+ bound per mole of the mammalian MT are located in two separate metal clusters, one containing 4 metal ions and the other, 3 metal ions. In the invertebrate (Scylla serrata) MT, similar studies have revealed that the 6 g-atoms of bound Cd2+ are distributed in two distinct 3-metal clusters while in Neurospora MT, the 3 g-atoms of bound Cd2+ are arranged in a pseudo 3-metal cluster. With the exception of one of the Cd2+ sites in this latter cluster, all the Cd2+ ions are tetrahedrally coordinated to four cysteine thiolate ligands with single cysteinyl sulfurs bridging adjacent metals. These conclusions are based on the 113Cd chemical shift data and a detailed analysis of the observed 113Cd-113Cd scalar couplings by both homonuclear decoupling and 2D techniques. In addition, the 113Cd NMR studies have revealed significant differences in the affinity of different metal ions for the two mammalian metal clusters. For the 3-metal cluster, the affinity is found to decrease in the order Cu+ greater than Cd2+ greater than Zn2+ with Cd2+ greater than Zn2+ for the 4 metal cluster and Cd2+ (4-metal cluster) greater than Cd2+ (3-metal cluster). The 113Cd NMR data are currently being integrated with 500 MHz 2D 1H and 1H-113Cd chemical shift correlated multiple quantum data sets to more completely define the structural arrangement of the metal clusters in the tertiary structure of these proteins.
Language of Publication: English
Unique Identifier: 88029878

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MeSH Heading (Major): Metallothionein|*ME; Metals|*ME
MeSH Heading: Amino Acid Sequence; Animal; Cadmium|ME; Comparative Study; Copper|ME; Crabs; Cysteine; Human; Liver|AN; Molecular Sequence Data; Neurospora crassa|AN; Nuclear Magnetic Resonance; Protein Conformation; Rabbits; Saccharomyces cerevisiae|AN; Support, U.S. Gov't, P.H.S.; Zinc|ME

Publication Type: JOURNAL ARTICLE
Country of Publication: SWITZERLAND
CAS Registry/EC Number: 0 (Metals); 4371-52-2 (Cysteine); 7440-43-9 (Cadmium); 7440-50-8 (Copper); 7440-66-6 (Zinc); 9038-94-2 (Metallothionein)

Record A7 from database: MEDLINE
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Title: Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures.
Author: Hultberg B; Andersson A; Isaksson A
Address: Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Source: Toxicology, 1997 Feb, 117:2-3, 89-97
Abstract: Ions of metals such as copper, mercury, silver and cadmium are known to exhibit a high affinity for thiol groups and may therefore severely disturb many metabolic functions in the cell. Copper ions are also known to catalyse the formation of toxic oxygen species through a series of redox reactions. In the present study, we have determined the concentration of reduced and total glutathione, cysteine and homocysteine in a cell culture system (HeLa cell line) after addition of these metal ions. The main findings of the metal ion effect on the total thiol concentrations are that all metal ions increased the release of glutathione into the medium. Since the intracellular concentration of glutathione did not decrease under these conditions, the synthesis of glutathione must have been increased. In contrast to the other metal ions, copper ions also increased the release of homocysteine into the medium, possibly through interaction with S-adenosylhomocysteine hydrolase. The main findings of metal ion effects on reduced thiol are that, at concentrations not interfering with cell growth, mercury, silver and cadmium ions increased the concentration of extracellular reduced glutathione, possibly reflecting the increase of total glutathione in the medium. In contrast to the other metal ions, the addition of even very low amounts of copper ions (1 mumol/l) decreased the concentration of intra- and extracellular reduced thiols indicating oxidative stress.
Language of Publication: English
Unique Identifier: 97210824

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MeSH Heading (Major): Copper|*TO; Cysteine|*DE/ME; Glutathione|BI/*DE; Hela Cells|*DE/ME; Homocysteine|*DE/ME; Metals, Heavy|*TO
MeSH Heading: Animal; Cadmium|TO; Cations|TO; Human; Mercury|TO; Oxidation-Reduction; Oxidative Stress|DE; Silver|TO; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE
ISSN: 0300-483X
Country of Publication: IRELAND

Record A8 from database: MEDLINE
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Title: Affinity cleavage at the metal-binding site of phosphoenolpyruvate carboxykinase.
Author: Hlavaty JJ; Nowak T
Address: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Source: Biochemistry, 1997 Dec, 36:49, 15514-25
Abstract: Chicken liver phosphoenolpyruvate carboxykinase (PEPCK) was rapidly inactivated by micromolar concentrations of ferrous sulfate in the presence of ascorbate at pH 7.4. Omitting ascorbate or replacing the Fe2+ with Mn2+ or Mg2+ gives no inactivation. Mn2+, Mg2+, or Co2+ at 100-fold molar excess over Fe2+ offered complete protection from Fe2+/ascorbate-induced inactivation. The substrates PEP and GTP, but not OAA, GDP, or CO2, offered full protection from inactivation. The addition of 5 mM EDTA stopped further inactivation of the enzyme. Thermodynamic studies indicate that the inactive enzyme no longer binds Mn2+ but still had high affinity for GTP indicating that the inactivation process was specific for the metal site. A decrease in cysteine content was observed over time following PEPCK treatment with Fe2+ and ascorbate. The apparent first-order rate constant for free sulfhydryl loss (0.085 +/- 0.005 min-1) is similar to the apparent first-order rate constant for inactivation (0.067 +/- 0.005 min-1). Amino acid composition analysis revealed that cysteic acid was generated upon Fe2+/ascorbate addition to PEPCK. Native chicken liver PEPCK has an Mr of 67 kDa. SDS-PAGE of the inactivated enzyme showed the presence of two new bands at 31.7 and 35.3 kDa indicating that PEPCK was specifically cleaved at a single site. The rate of cleavage was slower than the rate of inactivation and fully inactivated enzyme was only 50% cleaved. The Fe2+/ascorbate-catalyzed inactivation was not solely due to protein cleavage. The protein fragments generated by cleavage were separated by C4 reverse phase HPLC. The cleavage exposed a new N-terminus which was identified to be the 35.3 kDa C-terminal half of PEPCK. Sequencing of the fragments indicated that the site of cleavage was between Asp296 and Ile297. These results indicate that Asp296 is involved in metal chelation. This agrees with previous studies [Hlavaty, J. J., & Nowak, T. (1997) Biochemistry 36, 3389-3403] that suggested that Asp295 and Asp296 are involved in metal binding.
Language of Publication: English
Unique Identifier: 98060805

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MeSH Heading (Major): Metals|*ME; Phosphoenolpyruvate Carboxykinase (GTP)|AI/IP/*ME
MeSH Heading: Amino Acid Sequence; Animal; Ascorbic Acid|PD; Binding Sites; Chickens; Chromatography, High Pressure Liquid; Cysteine|CH; Free Radical Scavengers; Guanosine Triphosphate|ME; Human; Hydrolysis; Kinetics; Liver|EN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tryptophan|CH

Publication Type: JOURNAL ARTICLE
ISSN: 0006-2960
Country of Publication: UNITED STATES

Record A9 from database: MEDLINE
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Title: Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase [see comments]
Author: Gitschier J; Moffat B; Reilly D; Wood WI; Fairbrother WJ
Address: Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Source: Nat Struct Biol, 1998 Jan, 5:1, 47-54
Abstract: Menkes disease is an X-linked disorder in copper transport that results in death during early childhood. The solution structures of both apo and Ag(I)-bound forms of the fourth metal-binding domain (mbd4) from the Menkes copper-transporting ATPase have been solved. The 72-residue mbd4 has a ferredoxin-like beta alpha beta beta alpha beta fold. Structural differences between the two forms are limited to the metal-binding loop, which is disordered in the apo structure but well ordered in the Ag(I)-bound structure. Ag(I) binds in a linear bicoordinate manner to the two Cys residues of the conserved GMTCxxC motif; Cu(I) likely coordinates in a similar manner. Menkes mbd4 is thus the first bicoordinate copper-binding protein to be characterized structurally. Sequence comparisons with other heavy-metal-binding domains reveal a conserved hydrophobic core and metal-binding motif.
Language of Publication: English
Unique Identifier: 98100082

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MeSH Heading (Major): Adenosinetriphosphatase|CH/*UL; Carrier Proteins|CH/*UL; Copper|*
MeSH Heading: Amino Acid Sequence; Apoproteins|CH/UL; Binding Sites; Cysteine|CH; Human; Membrane Proteins|UL; Metals, Heavy; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Solutions; Structure-Activity Relationship; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE
ISSN: 1072-8368
Country of Publication: UNITED STATES

Record A10 from database: MEDLINE
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Title: Role of sulfhydryls in the hepatotoxicity of organic and metallic compounds.
Author: Klaassen CD; Bracken WM; Dudley RE; Goering PL; Hazelton GA; Hjelle JJ
Address
Source: Fundam Appl Toxicol, 1985 Oct, 5:5, 806-15
Abstract: Endogenous sulfhydryl compounds serve a critical role in maintaining the function and viability of living systems. Glutathione (GSH) is the most abundant of these nonprotein thiols. During the past decade it has been demonstrated that sulfhydryls such as GSH also serve an important role in protecting vital nucleophilic sites in the liver from electrophilic attack by numerous classes of reactive chemicals. Organocompounds such as bromobenzene and acetaminophen which undergo microsomal metabolism yield reactive intermediates that are specifically inactivated by conjugation with sulfhydryls in the form of GSH. Thus, for organocompounds GSH is extremely important in protecting against toxic insults. More recently, other sulfhydryl compounds also have been found to serve a specific but as yet less defined role in protecting biological systems against chemically induced injury. Metals such as cadmium have a high affinity for sulfhydryls and the metal binding protein metallothionein binds cadmium with high affinity. The highly specific association of the metal with this sulfhydryl-enriched protein serves to effectively sequester the reactive cadmium ion. The central role of sulfhydryl equivalents in the detoxication of organo- and metallocompounds is similar; however, the mechanism by which this is achieved is fundamentally different.
Language of Publication: English
Unique Identifier: 86056693

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MeSH Heading (Major): Hepatitis, Toxic|*ME; Metals|*TO; Sulfhydryl Compounds|*ME
MeSH Heading: Acetaminophen|TO; Animal; Biotransformation; Bromobenzenes|TO; Cadmium Poisoning|ME; Cysteine|PD; Cytochrom

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