DOCSLIB.ORG

Role of Metallothioneins in Copper Transport in Patients with Menkes Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of Metallothioneins in Copper Transport in Patients with Menkes Syndrome ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 8, No. 4 Copyright © 1978, Institute for Clinical Science Role of Metallothioneins in Copper Transport in Patients with Menkes Syndrome ADOLFO D. GARNICA, M.D., W. Y. CHAN, Ph.D.* and OWEN M. RENNERT, M.D.* Division of Genetics, Department of Pediatrics, University o f Florida College of Medicine, Gainesville, FL 32610 and Department o f Pediatrics, Health Science Center, University of Oklahoma, Oklahoma City, OK 73190 ABSTRACT Fibroblasts from infants with Menkes kinky hair syndrome, which accumu­ late excessive quantities of copper, are thought to represent a disorder of copper storage or transport. Because of this abnormality, it was thought that they might provide a useful system for investigation of the presumed storage or transport protein metallothionein. Data are presented which are consist­ ent with defective copper efflux from the mutant cells. Because of the more specific role of metallothionein in cadmium detoxification, studies of cad­ mium metabolism were undertaken which demonstrated abnormal cadmium retention and metallothionein induction in the mutant cells. The association, therefore, of a defect of cadmium metabolism and storage with an abnormality of copper efflux provides evidence implicating metallothionein in copper transport for fibroblasts. Introduction tute significant components. Metallothio­ nein synthesis in response to metal loading The metallothioneins are zinc, copper in animals implicates them in heavy metal and cadmium-binding intracellular pro­ detoxification and/or essential trace metal teins of low molecular weight, which con­ m etabolism .5, 10, 21, 28,30 M etallothionein tain 30 to 35 percent cysteine and 6 to 11 synthesis occurs in response to toxic metal percent metal bound to cysteinyl side challenge. However, the liver content of chains by mercaptide bonds. They occur in zinc, an essential trace metal, has been multiple tissues in some species, in forms reported to be an important determinant of of varying amino acid composition, de­ the concentration of metallothionein-type spite which their biological function has not proteins.1,5,11,31 been established.20,22 In human liver, zinc The function of metallothionein in in­ is the principal metal constituent, al­ tracellular copper transport was suggested though copper and cadmium also consti­ by the identification and isolation of a 302 0091-7370/78/0700-0302 $01.20 © Institute for Clinical Science, Inc. ROLE OF METALLOTHIONEINS IN PATIENTS WITH MENKES SYNDROME 3 0 3 cytosol protein of an estimated 10,000 Amersham/Searle. 64 Cu and 109 Cd were molecular weight which apparently is counted in a gamma counter.* Metal involved in intestinal copper absorp­ analysis was performed with an atomic tion.9, 10,36,37 A copper-binding cytosol pro­ absorption spectrophotometerf equip­ tein of molecular weight 11,000, the same ped with graphite furnace. Protein was estimated size as metallothionein, has determined by the method of Lowry been implicated in the cellular uptake of et a l.23 copper.36,37 On the basis of similarities be­ tween this protein fraction and the metal- C o p p e r -D o s e R e s p o n s e lothioneins, a role has been postulated for metallothionein in intracellular copper Copper sulfate was added to confluent transport.9,10,37 fibroblast cultures to achieve copper con­ Copper is potentially toxic to all forms centrations of a 2 to 40 ju.g per ml. The of life, especially those having no capac­ cultures were incubated for 48 hours at ity to limit its uptake. In such instances, 37° C, trypsinized and homogenized, and susceptibility to copper toxicity, of the supernatant copper and protein necessity, becomes a function of cellular measured. excretory efficiency. The viability of cul­ tured fibroblasts, despite their permea­ C a d m iu m C o n t e n t bility to copper, thus implies the function of efficient homeostatic mechanisms, and Cadmium chloride was added to basal the accumulation of excessive amounts of culture medium to achieve cadmium copper by skin fibroblasts from individu­ concentrations of 0.1 to 1.1 meg per ml. als with Menkes kinky hair syndrome Confluent fibroblast cultures were incu­ might represent a failure of such mecha­ bated for 48 hours at 37°C in medium of nisms.6,13,14,16 This report reviews studies increasing cadmium concentration, then attempting to clarify the molecular basis harvested, homogenized and the super­ of this abnormality and the role of metal­ natant protein and cadmium determined. lothionein in its pathogenesis. A decrease in copper efflux from Menkes syndrome C a d m iu m a n d C o p p e r U p t a k e fibroblasts is recorded, along with an aberrant response to cadmium challenge, Precisely 17 ju.Ci o f64Cu were added to which implies an inborn defect in copper confluent cultures in 10 ml of medium, and cadmium metabolism. These obser­ the Cu++ concentration of which was ad­ vations support the intracellular detoxifi­ justed to 9 /xg per ml with CuS04. Cad­ cation and transport functions postulated mium, if present, was added to a concen­ for metallothionein.5,1 u21,32,35 tration of 0.09 fig per ml. The cultures were incubated at 37° C for one to 10 hours, harvested, homogenized, the pro­ Materials and Methods tein content of the lysate determined and Skin fibroblast cultures were explanted the 64Cu counted. 109 Cd uptake by cul­ from three infants w'ith Menkes kinky tured fibroblasts were examined at 37°C. hair syndrome. Two additional mutant Four nCi of109 Cd were added to the cul­ cultures and control cultures were ob­ ture medium and the Cd++ concentration tained from the Human Genetic Cell Re­ adjusted to 0.56 ng per ml with CdCl2. pository and the American Type Culture Collection. 64Cu was obtained from the * Packard Model S210. New England Nuclear and 109Cd from t Perkin-Elmer Model 306. 304 GARNICA, CHAN AND RENNERT C o ppe r E f f l u x concentrations of 10 through 15 meg per ml, the copper content of both cultures in­ Cultures were pulse-labeled with 16.7 creased above the baseline levels, while ju.Ci of 64Cu at 37°C for 20 hours, then that of the Menkes syndrome cells re­ transferred to non-radioactive medium. mained greater than the normal (P < Cultures were harvested and analyzed for 64 Cu and protein one to 10 hours after the 0.04). At medium concentrations equal to or above 20 meg per ml, the copper con­ medium change. tent of the normal cells was not signifi­ Statistical differences were examined cantly different from that of the mutant for significance using a t-test for paired cells. data. These observations suggest that copper Results uptake by the mutant fibroblasts is at least equal to that of normal fibroblasts. F ib r o b l a st C o p p e r a n d C adm ium Furthermore, they imply that the copper C o n t e n t regulatory mechanisms in normal fibro­ Cultured Menkes syndrome fibroblasts blasts function effectively up to a medium are morphologically normal but have a copper concentration of approximately 15 diminished tolerance to copper.4 The in­ meg per ml, while those of Menkes syn­ creased sensitivity of these cells to cop­ drome fibroblasts are abnormal at all con- per toxicity is associated with increased concentrations. An inconsistency in the intracellular copper content.13,16 In basal general relationship between medium cop­ culture medium (copper concentration per concentration and fibroblast copper 48.70 ± 20.0 ng per ml) the copper con­ content involving both cell lines is appa­ tent of normal cells was 108 ng per mg rent at a medium concentration of 1 meg cell protein, while that of the mutant fi­ per ml, which most plausibly may be ex­ broblasts was 310 ng per mg (table I). As plained in terms of a ten-fold error in di­ the copper concentration of the medium lution, since the values at one and 10 meg was gradually increased, the copper con­ per ml are essentially the same for both tent of neither cell culture increased sig­ cultures. nificantly until the medium copper con­ As the cadmium concentration of the centration exceeded 6 meg per ml. At culture medium was increased from basal T A B L E I Copper and Cadmium Content of Cultured Skin Fibroblasts Medium (Cu++) Copper Content*+ Medium (Cd++) Cadmium Content *§ meg p e r ml MS* (n=7) N orm al (n=4) m eg p e r ml MS (n-5) Normal (n=4) + + 0 3 1 0 + 6411 1 0 8 ± 2 1 0 2 3 . 6 6.4 1 ! 2 3 . 5 93 + 1 6 0 5 + 1 8 9 2 2 2 + 74 0 . 1 1 9 2 4 4 1 8 0 ± 8 4 + + 4 2 5 3 + 4 6 1 0 6 + 2 0 0 . 3 8 6 6 3 9 2 2 4 1 4 9 + + 6 2 6 4 ± 5 0 1 5 4 + 37 0 . 5 1 1 6 5 2 1 6 6 2 0 2 0 7 1 0 6 3 7 + 2 2 9 2 5 9 + 94 0 . 7 1 0 7 3 + 3 6 3 7 6 5 ± 93 + + 15 8 0 4 + 1 1 1 4 5 2 + 1 3 3 0 . 9 1 4 3 4 1 5 7 8 0 1 1 1 3 + 2 0 9 7 5 + 3 3 1 1 0 8 0 + 1 5 1 1 . 1 1 0 1 8 + 2 2 8 6 5 5 1 2 3 25 1 1 3 9 + 1 9 5 1 9 1 3 + 6 0 8 30 1 3 6 7 + 332 1 5 5 3 + 383 35 2 1 5 0 + 1 0 1 2 2 0 8 6 + 5 1 6 40 2 2 2 2 + 4 1 8 2 4 7 5 + 7 2 0 *Units expressed as ng metal per mg cell protein.
Load more

Recommended publications
  • Metallothionein-Protein Interactions
    DOI 10.1515/bmc-2012-0049 BioMol Concepts 2013; 4(2): 143–160 Review S í lvia Atrian * and Merc è Capdevila Metallothionein-protein interactions Abstract: Metallothioneins (MTs) are a family of univer- Introduction sal, small proteins, sharing a high cysteine content and an optimal capacity for metal ion coordination. They take Metallothioneins (MTs) are a family of small ( < 10 kDa), part in a plethora of metal ion-related events (from detoxi- extremely heterogeneous proteins, sharing a high cysteine fication to homeostasis, storage, and delivery), in a wide content (15 – 30 % ) that confers them an optimal capacity range of stress responses, and in different pathological for metal ion coordination. After their discovery in horse processes (tumorigenesis, neurodegeneration, and inflam- kidneys by Bert Vallee in 1957 (1) , MTs have been identi- mation). The information on both intracellular and extra- fied and characterized in most prokaryotic and all eukary- cellular interactions of MTs with other proteins is here otic organisms. Besides metal ion detoxification, they comprehensively reviewed. In mammalian kidney, MT1/ have been related to a plethora of physiological events, MT2 interact with megalin and related receptors, and with from the homeostasis, storage, and delivery of physiologi- the transporter transthyretin. Most of the mammalian MT cal metals, to the defense against a wide range of stresses partners identified concern interactions with central nerv- and pathological processes (tumor genesis, neurodegen- ous system (mainly brain) proteins, both through physical eration, inflammation, etc.). It is now a common agree- contact or metal exchange reactions. Physical interactions ment among MT researchers that the ambiguity when mainly involve neuronal secretion multimers.
    [Show full text]
  • Eucaryotic Metallothioneins: Proteins, Gene Regulation and Copper Homeostasis
    Cah. Biol. Mar. (2001) 42 : 125-135 Eucaryotic metallothioneins: proteins, gene regulation and copper homeostasis. Alejandra MOENNE Laboratorio de Biología Molecular, Departamento de Ciencias Biológicas, Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40 correo 33, Santiago, Chile. Fax number: 56-2-6812108 - E-mail: [email protected] Abstract: Heavy metals such as copper, iron and zinc are essential for eucaryotic cell viability and they are required only in trace amounts. High concentrations of these metals are toxic for the cells and they trigger different molecular response mechanisms. One of the best studied of such responses involves the synthesis of metallothioneins (MTs) which are low molecular weight, cysteine-rich proteins that bind heavy metals by means of their cysteine residues. MTs have been purified from different eucaryotic cells and their structural and heavy metal binding properties have been determined. MT genes have been cloned from animal cells, fungi, plants and algae and their transcriptional activation by heavy metals has been characterized. The overexpression of MTs results in the accumulation of heavy metals in the cells. The best studied model for copper tolerance and homeostasis is the yeast Saccharomyces cerevisiae. In this fungus, high concentrations of copper activate transcription of the gene coding for CUP1 MT. This process involves the binding of ACE1 transcription factor to the promoter of cup-1 gene. ACE1 directly binds copper ions and undergoes a conformational change that allows its binding to the promoter region. On the other hand, copper starvation triggers the transcriptional activation of at least two copper transporter genes and a copper reductase gene.
    [Show full text]
  • Summary of Supportive Science Regarding Thimerosal Removal
    Summary of Supportive Science Regarding Thimerosal Removal Updated December 2012 www.safeminds.org Science Summary on Mercury in Vaccines (Thimerosal Only) SafeMinds Update – December 2012 Contents ENVIRONMENTAL IMPACT ................................................................................................................................. 4 A PILOT SCALE EVALUATION OF REMOVAL OF MERCURY FROM PHARMACEUTICAL WASTEWATER USING GRANULAR ACTIVATED CARBON (CYR 2002) ................................................................................................................................................................. 4 BIODEGRADATION OF THIOMERSAL CONTAINING EFFLUENTS BY A MERCURY RESISTANT PSEUDOMONAS PUTIDA STRAIN (FORTUNATO 2005) ......................................................................................................................................................................... 4 USE OF ADSORPTION PROCESS TO REMOVE ORGANIC MERCURY THIMEROSAL FROM INDUSTRIAL PROCESS WASTEWATER (VELICU 2007)5 HUMAN & INFANT RESEARCH ............................................................................................................................ 5 IATROGENIC EXPOSURE TO MERCURY AFTER HEPATITIS B VACCINATION IN PRETERM INFANTS (STAJICH 2000) .................................. 5 MERCURY CONCENTRATIONS AND METABOLISM IN INFANTS RECEIVING VACCINES CONTAINING THIMEROSAL: A DESCRIPTIVE STUDY (PICHICHERO 2002) ......................................................................................................................................................
    [Show full text]
  • Metallothionein-3 As a Multifunctional Player in the Control of Cellular Processes and Diseases Jae-Young Koh1,2 and Sook-Jeong Lee3*
    Koh and Lee Molecular Brain (2020) 13:116 https://doi.org/10.1186/s13041-020-00654-w REVIEW Open Access Metallothionein-3 as a multifunctional player in the control of cellular processes and diseases Jae-Young Koh1,2 and Sook-Jeong Lee3* Abstract Transition metals, such as iron, copper, and zinc, play a very important role in life as the regulators of various physiochemical reactions in cells. Abnormal distribution and concentration of these metals in the body are closely associated with various diseases including ischemic seizure, Alzheimer’s disease, diabetes, and cancer. Iron and copper are known to be mainly involved in in vivo redox reaction. Zinc controls a variety of intracellular metabolism via binding to lots of proteins in cells and altering their structure and function. Metallothionein-3 (MT3) is a representative zinc binding protein predominant in the brain. Although the role of MT3 in other organs still needs to be elucidated, many reports have suggested critical roles for the protein in the control of a variety of cellular homeostasis. Here, we review various biological functions of MT3, focusing on different cellular molecules and diseases involving MT3 in the body. Keywords: Autophagy, Alzheimer’s disease, Lysosome, Metallothionein-3, Neurodegenerative disease, Oxidative stress, Zinc Introduction Metallothioneins (MTs) are proteins that bind or re- Intracellular transition metals exist in various forms- lease cellular transition metals, an interaction that de- free or attached to proteins or organelles. Most metals pends on specific cell situations. MTs were first reported in the cells are involved in diverse cellular function, in- by Vallee and Margoshe as Cd-binding protein from cluding the recycling of organelles and proteins as well horse renal cortex [1].
    [Show full text]
  • Scientific Papers Showing Linking Thimerosal Exposure to Autism
    Scientific Papers Showing Linking Thimerosal Exposure to Autism April 6, 2015 Brian S. Hooker, Ph.D., P.E. 1. Rose et al. 2015 J Toxicol “Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines” PMID 25688267. In a comparison of lymphoblast cells from children with autism and matched non-autistic controls, a significantly higher number of “autistic” cell lines showed a reduction in ATP- linked respiration, maximal respiratory capacity and reserve capacity when exposed to mercury as compared to control cell lines. This supports the notion that a subset of individuals with autism may be vulnerable to mitochondrial dysfunction via thimerosal exposure. 2. Geier et al. 2015 Clin Chim Acta “Thimerosal: Clinical, Epidemiologic and Biochemical Studies,” PMID 25708367. This review article includes a section on numerous papers linking thimerosal exposure via infant vaccines to autism. This also includes a critique of studies from the U.S. Centers for Disease Control that deny any type of link. 3. Hooker et al. 2014 BioMed Research International, “Methodological Issues and Evidence of Malfeasance In Research Purporting to Show that Thimerosal-Containing Vaccines are Safe” http://dx.doi.org/10.1155/2014/247218. This review article shows methodological flaws in six separate CDC studies claiming that thimerosal does not cause autism. In three specific instances (Madsen et al. 2003, Verstraeten et al. 2003 and Price et al. 2010) evidence of malfeasance on the part of CDC scientists is shown. Background data (not reported in print) from these three publications suggest a strong link between thimerosal exposure and autism.
    [Show full text]
  • The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism
    International Journal of Molecular Sciences Review The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism Artur Kr˛ezel˙ 1 and Wolfgang Maret 2,* 1 Department of Chemical Biology, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland; [email protected] 2 Division of Diabetes and Nutritional Sciences, Department of Biochemistry, Faculty of Life Sciences and Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, UK * Correspondence: [email protected]; Tel.: +44-020-7848-4264; Fax: +44-020-7848-4195 Academic Editor: Eva Freisinger Received: 25 April 2017; Accepted: 3 June 2017; Published: 9 June 2017 Abstract: Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn2+, the loading of exocytotic vesicles with zinc species, and the control of Zn2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn2+ and Cu+ match the biological requirements for controlling—binding and delivering—these cellular metal ions, thus completing a 60-year search for their functions.
    [Show full text]
  • The Heavy Metal-Regulatory Transcription Factor MTF-1
    Review articles Putting its fingers on stressful situations: the heavy metal-regulatory transcription factor MTF-1 P. Lichtlen** and W. Schaffner* Summary and the liver. They have the ability to bind heavy metals such It has been suggested that metallothioneins, discovered as zinc, cadmium, copper, nickel and cobalt (reviewed in about 45 years ago, play a central role in heavy metal metabolism and detoxification, and in the management of Ref. 7). Metallothioneins are involved in homeostatic regula- various forms of stress. The metal-regulatory transcrip- tion of zinc concentrations and also for the detoxification of tion factor-1 (MTF-1) was shown to be essential for basal non-essential heavy metals. As an example of the latter, and heavy metal-induced transcription of the stress- mammals store all cadmium taken up in food in a form tightly responsive metallothionein-I and metallothionein-II. Re- bound to metallothioneins, where it remains with a half-life of cently it has become obvious that MTF-1 has further roles (8) in the transcriptional regulation of genes induced by approximately 15 years in humans. The expression of the various stressors and might even contribute to some major metallothionein genes (MT-I and MT-II ) is induced at the aspects of malignant cell growth. Furthermore, MTF-1 is level of transcription by heavy metal load.(9) As shown by an essential gene, as mice null-mutant for MTF-1 die in Palmiter and colleagues, the promoter region of these metal- utero due to liver degeneration. We describe here the lothionein genes contain so-called metal responsive elements state of knowledge on the complex activation of MTF-1, and propose a model with MTF-1 as an interconnected (MREs) that can confer metal-inducibility to any reporter gene (10,11) cellular stress-sensor protein involved in heavy metal when placed in a promoter position or at a remote metabolism, hepatocyte differentiation and detoxifica- enhancer position.(12) Several laboratories, including ours, tion of toxic agents.
    [Show full text]
  • Mapping the Salt Stress-Induced Changes in the Root Mirnome in Pokkali Rice
    biomolecules Article Mapping the Salt Stress-Induced Changes in the Root miRNome in Pokkali Rice Kavita Goswami 1,2, Deepti Mittal 1, Budhayash Gautam 2 , Sudhir K. Sopory 1 and Neeti Sanan-Mishra 1,* 1 Plant RNAi Biology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India; [email protected] (K.G.); [email protected] (D.M.); [email protected] (S.K.S.) 2 Department of Computational Biology and Bioinformatics, Jacob School of Biotechnology and Bioengineering, Sam Higginbottom university of Agriculture, Technology and Sciences, Prayagraj (Formally Allahabad) 211007, India; [email protected] * Correspondence: [email protected]; Tel.: +91-11-2674-1358/61; Fax: +91-11-2674-2316 Received: 9 January 2020; Accepted: 6 March 2020; Published: 25 March 2020 Abstract: A plant’s response to stress conditions is governed by intricately coordinated gene expression. The microRNAs (miRs) have emerged as relatively new players in the genetic network, regulating gene expression at the transcriptional and post-transcriptional level. In this study, we performed comprehensive profiling of miRs in roots of the naturally salt-tolerant Pokkali rice variety to understand their role in regulating plant physiology in the presence of salt. For comparisons, root miR profiles of the salt-sensitive rice variety Pusa Basmati were generated. It was seen that the expression levels of 65 miRs were similar for roots of Pokkali grown in the absence of salt (PKNR) and Pusa Basmati grown in the presence of salt (PBSR). The salt-induced dis-regulations in expression profiles of miRs showed controlled changes in the roots of Pokkali (PKSR) as compared to larger variations seen in the roots of Pusa Basmati.
    [Show full text]
  • Balance Between Metallothionein and Metal Response Element Binding Transcription Factor 1 Is Mediated by Zinc Ions (Review)
    1582 MOLECULAR MEDICINE REPORTS 11: 1582-1586, 2015 Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (Review) GANG DONG1, HONG CHEN2, MEIYU QI3, YE DOU2 and QINGLU WANG2 1Department of Oral Medicine; 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Shandong Wanjie Medical College, Zibo, Shandong 255213; 3Cattle Research Department, Animal Husbandry Institute, Heilongjiang Academy of Agricultural Sciences, Harbin, Heilongjiang 150086, P.R. China Received February 14, 2014; Accepted October 24, 2014 DOI: 10.3892/mmr.2014.2969 Abstract. Metal ion homeostasis and heavy metal detoxifica- 1. Introduction tion systems are regulated by certain genes associated with metal ion transport. Metallothionein (MT) and metal response Cells adjust their gene expression profile in order to rapidly element binding transcription factor 1 (MTF-1) are important adapt to various forms of stress. Therefore, stress-responsive regulatory proteins involved in the mediation of intracellular transcription factors are mainly regulated at the post-trans- metal ion balance. Differences in the zinc-binding affinities lational level by modulating activity, stability or subcellular of the zinc fingers of MTF-1 and the α- and β-domains of MT localization (1). Certain transcription factors predominantly facilitate their regulation of Zn2+ concentration. Alterations in localize to the cytoplasm and translocate to the nucleus when the intracellular concentration of Zn2+ influence the MTF-1 required (1). The zinc ion (Zn2+) is an important metal ion zinc finger number, and MTF-1 containing certain zinc finger involved in the regulation of transcription factors. Zn2+ and numbers regulates the expression of corresponding target other essential metal ions have diverse roles in numerous genes.
    [Show full text]
  • Heavy Metals Detoxification: a Review of Herbal Compounds for Chelation Therapy in Heavy Metals Toxicity
    J Herbmed Pharmacol. 2019; 8(2): 69-77. http://www.herbmedpharmacol.com doi: 10.15171/jhp.2019.12 Journal of Herbmed Pharmacology Heavy metals detoxification: A review of herbal compounds for chelation therapy in heavy metals toxicity Reza Mehrandish1, Aliasghar Rahimian2, Alireza Shahriary1* ID 1Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiatallah University of Medical Sciences, Tehran, Iran 2Department of Medical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran A R T I C L E I N F O A B S T R A C T Article Type: Some heavy metals are nutritionally essential elements playing key roles in different Review physiological and biological processes, like: iron, cobalt, zinc, copper, chromium, molybdenum, selenium and manganese, while some others are considered as the potentially toxic elements in Article History: high amounts or certain chemical forms. Nowadays, various usage of heavy metals in industry, Received: 30 December 2018 agriculture, medicine and technology has led to a widespread distribution in nature raising Accepted: 15 January 2019 concerns about their effects on human health and environment. Metallic ions may interact with cellular components such as DNA and nuclear proteins leading to apoptosis and carcinogenesis Keywords: arising from DNA damage and structural changes. As a result, exposure to heavy metals through Herbal plants ingestion, inhalation and dermal contact causes several health problems such as, cardiovascular Heavy metals diseases, neurological and neurobehavioral abnormalities, diabetes, blood abnormalities and Chelation various types of cancer. Due to extensive damage caused by heavy metal poisoning on various Detoxification organs of the body, the investigation and identification of therapeutic methods for poisoning with heavy metals is very important.
    [Show full text]
  • Structural Motifs of Novel Metallothionein Proteins
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository 4-25-2012 12:00 AM Structural Motifs of Novel Metallothionein Proteins Duncan E K Sutherland The University of Western Ontario Supervisor Dr. Martin J. Stillman The University of Western Ontario Graduate Program in Chemistry A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Duncan E K Sutherland 2012 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Biochemistry Commons, Inorganic Chemistry Commons, and the Molecular Biology Commons Recommended Citation Sutherland, Duncan E K, "Structural Motifs of Novel Metallothionein Proteins" (2012). Electronic Thesis and Dissertation Repository. 489. https://ir.lib.uwo.ca/etd/489 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. i Structural Motifs of Novel Metallothionein Proteins (Spine title: Structural Motifs of Metallothionein) (Thesis format: Integrated-Article) By Duncan Ewan Keith Sutherland Graduate Program in Chemistry Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada April, 2012 © Duncan Ewan Keith Sutherland 2012 School of Graduate and Postdoctoral Studies
    [Show full text]
  • Metallothionein Ill Is Expressed in Neurons That Sequester Zinc in Synaptic Vesicles
    The Journal of Neuroscience, October 1994, 14(10): 59445857 Metallothionein Ill Is Expressed in Neurons That Sequester Zinc in Synaptic Vesicles Brian A. Masters,Q Carol J. Quaife,* Jay C. Erickson,* Edward J. Kelly,* Glenda J. Froelick,* Brian P. Zambrowicz,2-b Ralph L. Brinster,’ and Richard D. Palmiter* ‘Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and *Howard Hunhes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington 98195 MT-III, a brain-specific member of the metallothionein gene (Uchida et al., 1991; Palmiter et al., 1992), and MT-IV, an family, binds zinc and may facilitate the storage of zinc in isoform that is restricted to keratinizing epithelia (Quaife et al., neurons. The distribution of MT-III mRNA within the adult 1994). MTs have been postulated to protect against metal tox- brain was determined by solution and in situ hybridization icity (Webb, 1979; Beach and Palmiter, 1981; Durnam and and compared to that of MT-I mRNA. MT-III mRNA is partic- Palmiter, 1987; Masters et al., 1994) and oxygen radicals (Thor- ularly abundant within the cerebral cortex, hippocampus, nalley and Vasak, 1985; Basu and Lazo, 1990; Hart et al., 1990; amygdala, and nuclei at base of the cerebellum. Transgenic Tamai et al., 1993) regulate metal homeostasis,and participate mice generated using 11.5 kb of the mouse MT-III 5’ flanking in the biosynthesis of metalloproteins (Bremner, 1991; Suzuki region fused to the E. colilacZgene express&galactosidase et al., 1993). in many of the same regions identified by in situ hybridiza- The presenceand distribution of MT-I and MT-II in the brain tion.
    [Show full text]