Skip to main content
SpringerLink
Log in

Metal detoxification and homeostasis in Antarctic Notothenioids. A comparative survey on evolution, expression and functional properties of fish and mammal metallothioneins

  • REVIEW PAPER
  • Published:
Reviews in Environmental Science and Bio/Technology Aims and scope Submit manuscript

Abstract

Organisms from yeast to mammals contain cysteine-rich, heavy metal binding proteins termed metallothioneins. The putative roles of these proteins are trace metal homeostasis and detoxification of poisonous heavy metals. The highly conserved chemical composition and the structural constraints led to the conclusion that metallothioneins of different origin must display remarkably similar features. The present review aims at surveying the studies carried out on the metallothioneins of Antarctic Notothenioidei, a dominating fish group endowed of a number of striking adaptive characters, including reduced (or absent) hematocrit and presence of antifreeze glycoproteins. Given the unique peculiarities of the Antarctic environment, a comparative study of the features of notothenioid metallothioneins could provide new insights into the role of these proteins in physiology and toxicology. The results summarized here show that the metallothioneins of this fish group display a number of features at the level of evolution, expression pattern, structure and function remarkably different from those of mammal metallothioneins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Andrews GK (2000) Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol 59:95–104

    Article  PubMed  CAS  Google Scholar 

  • Auf der Maur A, Belser T, Elgar G, Georgiev O, Schaffner W (1999) Characterization of the transcription factor MTF-1 from the Japanese pufferfish (Fugu rubripes) reveals evolutionary conservation of heavy metal stress response. Biol Chem 380:175–185

    Article  PubMed  CAS  Google Scholar 

  • Bargelloni L, Ritchie PA, Patarnello T, Battaglia B, Lambert DM, Meyer A (1994) Molecular evolution at subzero temperatures: mitochondrial and nuclear phylogenies of fishes from Antarctica (suborder Notothenioidei), and the evolution of antifreeze glycopeptides. Mol Biol Evol 11:854–863

    PubMed  CAS  Google Scholar 

  • Bargelloni L, Scudiero R, Parisi E, Carginale V, Capasso C, Patarnello T (1999) Metallothioneins in antarctic fish: evidence for independent duplication and gene conversion. Mol Biol Evol 16:885–897

    PubMed  CAS  Google Scholar 

  • Blaise C, Gagne F, Pellerin J, Hansen PD, Trottier S (2002) Molluscan shellfish biomarker study of the Quebec, Canada, Saguenay Fjord with the soft-shell clam, Mya arenaria. Environ Toxicol 17:170–186

    Article  PubMed  CAS  Google Scholar 

  • Bonham K, Gedamu L (1984) Induction of metallothionein and metallothionein mRNA in rainbow-trout liver following cadmium treatment. Biosci Rep 4:633–642

    Article  PubMed  CAS  Google Scholar 

  • Brugnera E, Georgiev O, Radtke F, Heuchel R, Baker E, Sutherland GR, Schaffner W (1994) Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1. Nucleic Acids Res 22:3167–3173

    PubMed  CAS  Google Scholar 

  • Cai L, Satoh M, Tohyama C, Cherian MG (1999) Metallothionein in radiation exposure: its induction and protective role. Toxicology 132:85–98

    Article  PubMed  CAS  Google Scholar 

  • Cajaraville MP, Bebianno MJ, Blasco J, Porte C, Sarasquete C, Viarengo A (2000) The use of biomarkers to assess the impact of pollution in coastal environments of the Iberian Peninsula: a practical approach. Sci Total Environ 247:295–311

    Article  PubMed  CAS  Google Scholar 

  • Capasso C, Abugo O, Tanfani F, Scire A, Carginale V, Scudiero R, Parisi E, D’Auria S (2002) Stability and conformational dynamics of metallothioneins from the antarctic fish Notothenia coriiceps and mouse. Proteins 46:259–267

    Article  PubMed  CAS  Google Scholar 

  • Capasso C, Carginale V, Crescenzi O, Di Maro D, Parisi E, Spadaccini R, Temussi PA (2003a) Solution structure of MT_nc, a novel metallothionein from the Antarctic fish Notothenia coriiceps. Structure 11:435–443

    Article  CAS  Google Scholar 

  • Capasso C, Carginale V, Crescenzi O, Di Maro D, Spadaccini R, Temussi PA, Parisi E (2005) Structural and functional studies of vertebrate metallothioneins: cross-talk between domains in the absence of physical contact. Biochem J 391:95–103

    Article  PubMed  CAS  Google Scholar 

  • Capasso C, Carginale V, Scudiero R, Crescenzi O, Spadaccini R, Temussi PA, Parisi E (2003b) Phylogenetic divergence of fish and mammalian metallothionein: relationships with structural diversification and organismal temperature. J Mol Evol 57(Suppl 1):S250–257

    Article  CAS  Google Scholar 

  • Carginale V, Scudiero R, Capasso A, Capasso C, Passaretti G, di Prisco G, Kille P, Parisi E (1999) Accumulation of untranslated metallothionein mRNA in Antarctic hemoglobinless fish (icefish). In: Klaassen C (ed) Metallothionein IV. Birkhauser Verlag, Basel, pp 167–172

    Google Scholar 

  • Carginale V, Scudiero R, Capasso C, Capasso A, Kille P, di Prisco G, Parisi E (1998) Cadmium-induced differential accumulation of metallothionein isoforms in the Antarctic icefish, which exhibits no basal metallothionein protein but high endogenous mRNA levels. Biochem J 332(Pt 2):475–481

    PubMed  CAS  Google Scholar 

  • Chan KM (1994) PCR-cloning of goldfish and tilapia metallothionein complementary DNAs. Biochem Biophys Res Commun 205:368–374

    Article  PubMed  CAS  Google Scholar 

  • Chen WY, John JA, Lin CH, Lin HF, Wu SC, Lin CH, Chang CY (2004) Expression of metallothionein gene during embryonic and early larval development in zebrafish. Aquat Toxicol 69:215–227

    Article  PubMed  CAS  Google Scholar 

  • Cocca E, Ratnayake-Lecamwasam M, Parker SK, Camardella L, Ciaramella M, di Prisco G, Detrich 3rd HW (1995) Genomic remnants of alpha-globin genes in the hemoglobinless antarctic icefishes. Proc Natl Acad Sci USA 92:1817–1821

    Article  PubMed  CAS  ADS  Google Scholar 

  • Culotta VC, Hamer DH (1989) Fine mapping of a mouse metallothionein gene metal response element. Mol Cell Biol 9:1376–1380

    PubMed  CAS  Google Scholar 

  • D’Auria S, Carginale V, Scudiero R, Crescenzi O, Di Maro D, Temussi PA, Parisi E, Capasso C (2001) Structural characterization and thermal stability of Notothenia coriiceps metallothionein. Biochem J 354:291–299

    Article  PubMed  CAS  Google Scholar 

  • Dallinger R, Berger B, Gruber C, Hunziker P, Sturzenbaum S (2000) Metallothioneins in terrestrial invertebrates: structural aspects, biological significance and implications for their use as biomarkers. Cell Mol Biol (Noisy-le-grand) 46:331–346

    CAS  Google Scholar 

  • Dallinger R, Lagg B, Egg M, Schipflinger R, Chabicovsky M (2004) Cd accumulation and Cd-metallothionein as a biomarker in Cepaea hortensis (Helicidae, Pulmonata) from laboratory exposure and metal-polluted habitats. Ecotoxicology 13:757–772

    Article  PubMed  CAS  Google Scholar 

  • Dalton TP, Solis WA, Nebert DW, Carvan 3rd MJ (2000) Characterization of the MTF-1 transcription factor from zebrafish and trout cells. Comp Biochem Physiol B Biochem Mol Biol 126:325–335

    Article  PubMed  CAS  Google Scholar 

  • Dondero F, Piacentini L, Banni M, Rebelo M, Burlando B, Viarengo A (2005) Quantitative PCR analysis of two molluscan metallothionein genes unveils differential expression and regulation. Gene 345:259–270

    Article  PubMed  CAS  Google Scholar 

  • Eastman JT (1993) Antarctic fish biology. Evolution in a unique environment. Academic Press Inc., San Diego

    Google Scholar 

  • Friedman RL, Stark GR (1985) Alpha-interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature 314:637–639

    Article  PubMed  CAS  ADS  Google Scholar 

  • Huber KL, Cousins RJ (1993) Metallothionein expression in rat bone marrow is dependent on dietary zinc but not dependent on interleukin-1 or interleukin-6. J Nutr 123:642–648

    PubMed  CAS  Google Scholar 

  • Imbert J, Culotta V, Furst P, Gedamu L, Hamer D (1990) Regulation of metallothionein gene transcription by metals. Adv Inorg Biochem 8:139–164

    PubMed  CAS  Google Scholar 

  • Jiang LJ, Vasak M, Vallee BL, Maret W (2000) Zinc transfer potentials of the alpha- and beta-clusters of metallothionein are affected by domain interactions in the whole molecule. Proc Natl Acad Sci USA 97:2503–2508

    Article  PubMed  CAS  ADS  Google Scholar 

  • Kagi JHR (1993) Evolution, structure and chemical activity of class I metallothioneins: an overview. In: Suzuki KT, Imura N, Kimura M (eds) Metallothionein III. Birkhauser Verlag, Basel, pp 29–55

    Google Scholar 

  • Karin M (1985) Metallothioneins: proteins in search of function. Cell 41:9–10

    Article  PubMed  CAS  Google Scholar 

  • Kelly EJ, Quaife CJ, Froelick GJ, Palmiter RD (1996) Metallothionein I and II protect against zinc deficiency and zinc toxicity in mice. J Nutr 126:1782–1790

    PubMed  CAS  Google Scholar 

  • Klaassen CD, Lehman-McKeeman LD (1989) Regulation of the isoforms of metallothionein. Biol Trace Elem Res 21:119–129

    PubMed  CAS  Google Scholar 

  • Knapen D, Redeker ES, Inacio I, De Coen W, Verheyen E, Blust R (2005) New metallothionein mRNAs in Gobio gobio reveal at least three gene duplication events in cyprinid metallothionein evolution. Comp Biochem Physiol C Toxicol Pharmacol 140:347–355

    Article  PubMed  CAS  Google Scholar 

  • Koizumi S, Suzuki K, Ogra Y, Yamada H, Otsuka F (1999) Transcriptional activity and regulatory protein binding of metal-responsive elements of the human metallothionein-IIA gene. Eur J Biochem 259:635–642

    Article  PubMed  CAS  Google Scholar 

  • Kondoh M, Inoue Y, Atagi S, Futakawa N, Higashimoto M, Sato M (2001) Specific induction of metallothionein synthesis by mitochondrial oxidative stress. Life Sci 69:2137–2146

    Article  PubMed  CAS  Google Scholar 

  • Kumari MV, Hiramatsu M, Ebadi M (2000) Free radical scavenging actions of hippocampal metallothionein isoforms and of antimetallothioneins: an electron spin resonance spectroscopic study. Cell Mol Biol (Noisy-le-grand) 46:627–636

    CAS  Google Scholar 

  • Lakowicz JR, Laczko G, Gryczynski I, Cherek H (1986) Measurement of subnanosecond anisotropy decays of protein fluorescence using frequency-domain fluorometry. J Biol Chem 261:2240–2245

    PubMed  CAS  Google Scholar 

  • Liu J, Kadiiska MB, Corton JC, Qu W, Waalkes MP, Mason RP, Liu Y, Klaassen CD (2002) Acute cadmium exposure induces stress-related gene expression in wild-type and metallothionein-I/II-null mice. Free Radic Biol Med 32:525–535

    Article  PubMed  CAS  Google Scholar 

  • Marshall CJ (1997) Cold-adapted enzymes. Trends Biotechnol 15:359–364

    Article  PubMed  CAS  Google Scholar 

  • Mididoddi S, McGuirt JP, Sens MA, Todd JH, Sens DA (1996) Isoform-specific expression of metallothionein mRNA in the developing and adult human kidney. Toxicol Lett 85:17–27

    Article  PubMed  CAS  Google Scholar 

  • Munoz A, Petering DH, Shaw 3rd CF (2000a) Structure-reactivity relationships among metallothionein three-metal domains: role of non-cysteine amino acid residues in lobster metallothionein and human metallothionein-3. Inorg Chem 39:6114–6123

    Article  CAS  Google Scholar 

  • Munoz A, Petering DH, Shaw 3rd CF (2000b) The requirements for stable metallothionein clusters examined using synthetic lobster domains. Mar Environ Res 50:93–97

    Article  CAS  Google Scholar 

  • Murphy BJ, Sato BG, Dalton TP, Laderoute KR (2005) The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress. Biochem Biophys Res Commun 337:860–867

    Article  PubMed  CAS  Google Scholar 

  • Narula SS, Brouwer M, Hua Y, Armitage IM (1995) Three-dimensional solution structure of Callinectes sapidus metallothionein-1 determined by homonuclear and heteronuclear magnetic resonance spectroscopy. Biochemistry 34:620–631

    Article  PubMed  CAS  Google Scholar 

  • Nemer M, Wilkinson DG, Travaglini EC, Sternberg EJ (1985) Sea urchin metallothionein sequence: key to an evolutionary diversity. Proc Natl Acad Sci USA 82:4992–4994

    Article  PubMed  CAS  ADS  Google Scholar 

  • Nishimura N, Cam GR, Nishimura H, Tohyama C, Saitoh Y, Adelson DL (1996) Evidence for developmentally regulated transcriptional, translational and post-translational control of metallothionein gene expression in hair follicles. Reprod Fertil Dev 8:1089–1096

    Article  PubMed  CAS  Google Scholar 

  • Pan PK, Hou FY, Cody CW, Huang PC (1994) Substitution of glutamic acids for the conserved lysines in the alpha domain affects metal binding in both the alpha and beta domains of mammalian metallothionein. Biochem Biophys Res Commun 202:621–628

    Article  PubMed  CAS  Google Scholar 

  • Pauwels M, van Weyenbergh J, Soumillion A, Proost P, De Ley M (1994) Induction by zinc of specific metallothionein isoforms in human monocytes. Eur J Biochem 220:105–110

    Article  PubMed  CAS  Google Scholar 

  • Ren HW, Itoh N, Kanekiyo M, Tominaga S, Kohroki J, Hwang GS, Nakanishi T, Muto N, Tanaka K (2000) Two metallothioneins in the fresh-water fish, crucian carp (Carassius cuvieri): cDNA cloning and assignment of their expression isoforms. Biol Pharm Bull 23:145–148

    PubMed  CAS  Google Scholar 

  • Riggio M, Filosa S, Parisi E, Scudiero R (2003) Changes in zinc, copper and metallothionein contents during oocyte growth and early development of the teleost Danio rerio (zebrafish). Comp Biochem Physiol C Toxicol Pharmacol 135:191–196

    Article  PubMed  CAS  Google Scholar 

  • Robbins AH, Stout CD (1991) X-ray structure of metallothionein. Methods Enzymol 205:485–502

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Ortega MJ, Alhama J, Funes V, Romero-Ruiz A, Rodriguez-Ariza A, Lopez-Barea J (2002) Biochemical biomarkers of pollution in the clam Chamaelea gallina from south-Spanish littoral. Environ Toxicol Chem 21:542–549

    Article  PubMed  Google Scholar 

  • Romero-Isart N, Jensen LT, Zerbe O, Winge DR, Vasak M (2002) Engineering of metallothionein-3 neuroinhibitory activity into the inactive isoform metallothionein-1. J Biol Chem 277:37023–37028

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal MD, Albrecht ED, Pepe GJ (2004) Estrogen modulates developmentally regulated gene expression in the fetal baboon liver. Endocrine 23:219–228

    Article  PubMed  CAS  Google Scholar 

  • Rupp H, Weser U (1978) Circular dichroism of metallothioneins. A structural approach. Biochim Biophys Acta 533:209–226

    PubMed  CAS  Google Scholar 

  • Salgado MT, Stillman MJ (2004) Cu+ distribution in metallothionein fragments. Biochem Biophys Res Commun 318:73–80

    Article  PubMed  CAS  Google Scholar 

  • Samson SL, Gedamu L (1998) Molecular analyses of metallothionein gene regulation. Prog Nucleic Acid Res Mol Biol 59:257–288

    Article  PubMed  CAS  Google Scholar 

  • Sato M, Sasaki M, Hojo H (1994) Differential induction of metallothionein synthesis by interleukin-6 and tumor necrosis factor-alpha in rat tissues. Int J Immunopharmacol 16:187–195

    Article  PubMed  CAS  Google Scholar 

  • Scudiero R, Carginale V, Capasso C, Riggio M, Filosa S, Parisi E (2001) Structural and functional analysis of metal regulatory elements in the promoter region of genes encoding metallothionein isoforms in the Antarctic fish Chionodraco hamatus (icefish). Gene 274:199–208

    Article  PubMed  CAS  Google Scholar 

  • Scudiero R, Carginale V, Riggio M, Capasso C, Capasso A, Kille P, di Prisco G, Parisi E (1997) Difference in hepatic metallothionein content in Antarctic red-blooded and haemoglobinless fish: undetectable metallothionein levels in haemoglobinless fish is accompanied by accumulation of untranslated metallothionein mRNA. Biochem J 322(Pt 1):207–211

    PubMed  CAS  Google Scholar 

  • Scudiero R, Paolo De Prisco P, Camardella L, D’Avino R, di Prisco G, Parisi E (1992) Apparent deficiency of metallothionein in the liver of the Antarctic icefish Chionodraco hamatus. Identification and isolation of a zinc-containing protein unlike metallothionein. Comp Biochem Physiol B 103:201–207

    Article  PubMed  CAS  Google Scholar 

  • Scudiero R, Temussi PA, Parisi E (2005) Fish and mammalian metallothioneins: a comparative study. Gene 345:21–26

    Article  PubMed  CAS  Google Scholar 

  • Scudiero R, Verde C, Carginale V, Kille P, Capasso C, di Prisco G, Parisi E (2000) Tissue-specific regulation of metallothionin and metallothionein mRNA accumulation in the Antarctic notothenioid, Notothenia coriiceps. Polar Biol 23:17–23

    Article  Google Scholar 

  • Searle PF, Stuart GW, Palmiter RD (1987) Metal regulatory elements of the mouse metallothionein-I gene. Exp Suppl 52:407–414

    CAS  Google Scholar 

  • Seguin C, Prevost J (1988) Detection of a nuclear protein that interacts with a metal regulatory element of the mouse metallothionein 1 gene. Nucleic Acids Res 16:10547–10560

    PubMed  CAS  Google Scholar 

  • Thiele DJ (1992) Metal-regulated transcription in eukaryotes. Nucleic Acids Res 20:1183–1191

    PubMed  CAS  Google Scholar 

  • Uchida Y, Gomi F, Masumizu T, Miura Y (2002) Growth inhibitory factor prevents neurite extension and the death of cortical neurons caused by high oxygen exposure through hydroxyl radical scavenging. J Biol Chem 277:32353–32359

    Article  PubMed  CAS  Google Scholar 

  • Varshney U, Jahroudi N, Foster R, Gedamu L (1986) Structure, organization, and regulation of human metallothionein IF gene: differential and cell-type-specific expression in response to heavy metals and glucocorticoids. Mol Cell Biol 6:26–37

    PubMed  CAS  Google Scholar 

  • Vasconcelos MH, Tam SC, Hesketh JE, Reid M, Beattie JH (2002) Metal- and tissue-dependent relationship between metallothionein mRNA and protein. Toxicol Appl Pharmacol 182:91–97

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Mackay EA, Kurasaki M, Kagi JH (1994) Purification and characterisation of recombinant sea urchin metallothionein expressed in Escherichia coli. Eur J Biochem 225:449–457

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Mackay EA, Zerbe O, Hess D, Hunziker PE, Vasak M, Kagi JH (1995) Characterization and sequential localization of the metal clusters in sea urchin metallothionein. Biochemistry 34:7460–7467

    Article  PubMed  CAS  Google Scholar 

  • Willner H, Vasak M, Kagi JH (1987) Cadmium–thiolate clusters in metallothionein: spectrophotometric and spectropolarimetric features. Biochemistry 26:6287–6292

    Article  PubMed  CAS  Google Scholar 

  • Wright J, George S, Martinez-Lara E, Carpene E, Kindt M (2000) Levels of cellular glutathione and metallothionein affect the toxicity of oxidative stressors in an established carp cell line. Mar Environ Res 50:503–508

    Article  PubMed  CAS  Google Scholar 

  • Yan CH, Chan KM (2002) Characterization of zebrafish metallothionein gene promoter in a zebrafish caudal fin cell-line, SJD. 1. Mar Environ Res 54:335–339

    Article  PubMed  Google Scholar 

  • Yan CH, Chan KM (2004) Cloning of zebrafish metallothionein gene and characterization of its gene promoter region in HepG2 cell line. Biochim Biophys Acta 1679:47–58

    PubMed  CAS  Google Scholar 

  • You HJ, Lee KJ, Jeong HG (2002) Overexpression of human metallothionein-III prevents hydrogen peroxide- induced oxidative stress in human fibroblasts. FEBS Lett 521:175–179

    Article  PubMed  CAS  Google Scholar 

  • Zangger K, Shen G, Oz G, Otvos JD, Armitage IM (2001) Oxidative dimerization in metallothionein is a result of intermolecular disulphide bonds between cysteines in the alpha-domain. Biochem J 359:353–360

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The work reported in the present review was carried out thanks to the support provided by the “Programma Nazionale per le Ricerche in Antartide” (PNRA).

Author information

Authors and Affiliations

  1. CNR Institute of Protein Biochemistry, Via Pietro Castellino 111, 80131, Napoli, Italy

    Clemente Capasso, Vincenzo Carginale & Elio Parisi

  2. Department of Biological Sciences, University Federico II, Napoli, Italy

    Marilisa Riggio, Rosaria Scudiero & Francesca Trinchella

  3. National Institue for Medical Research, London, UK

    Piero Andrea Temussi

  4. Accademia dei Lincei, Roma, Italy

    Piero Andrea Temussi

Authors
  1. Clemente Capasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincenzo Carginale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marilisa Riggio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosaria Scudiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Piero Andrea Temussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Francesca Trinchella
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elio Parisi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elio Parisi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Capasso, C., Carginale, V., Riggio, M. et al. Metal detoxification and homeostasis in Antarctic Notothenioids. A comparative survey on evolution, expression and functional properties of fish and mammal metallothioneins. Rev Environ Sci Biotechnol 5, 253–267 (2006). https://doi.org/10.1007/s11157-006-0013-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11157-006-0013-0

Keywords

Search

Navigation