Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1994 Dec;102(Suppl 12):91–95. doi: 10.1289/ehp.94102s1291

Metallothionein induction as a measure of response to metal exposure in aquatic animals.

G Roesijadi 1
PMCID: PMC1566731  PMID: 7713043

Abstract

Metallothioneins (MTs) are considered central in the intracellular regulation of metals such as copper, zinc, and cadmium. Increased MT synthesis is associated with increased capacity for binding these metals and protection against metal toxicity. Recent advances in the biochemistry and molecular biology of MTs have facilitated research on MTs in aquatic species. For the bivalve mollusc Crassostrea virginica, a species frequently used in studies on the toxicology and environmental monitoring of metals, the primary structure for MT has been deduced from analysis of the proteins and cDNA. Procedures for analysis of MT synthesis and MT gene expression have been applied in studies of response to metal exposure. Induction of specific MT forms by Cd is concentration- and time-dependent. The levels of MT-bound metals exhibit a strong relationship with the cytosolic metal concentrations in a metal-exposed natural population of oysters. Ribonuclease protection assays using sequence-specific antisense RNA probes have shown that the MT mRNA structure in this natural population exhibits considerable individual variability in the 3'-untranslated region. Although yet to be substantiated, the possibility exists that the distribution of this variability may be related to the level of environmental metal contamination. One probe derived from the coding region is suitable for use in quantitative RPAs for oyster MT mRNAs.

Full text

PDF
91

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beach L. R., Palmiter R. D. Amplification of the metallothionein-I gene in cadmium-resistant mouse cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110–2114. doi: 10.1073/pnas.78.4.2110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonham K., Zafarullah M., Gedamu L. The rainbow trout metallothioneins: molecular cloning and characterization of two distinct cDNA sequences. DNA. 1987 Dec;6(6):519–528. doi: 10.1089/dna.1987.6.519. [DOI] [PubMed] [Google Scholar]
  3. Brouwer M., Brouwer-Hoexum T. Interaction of copper-metallothionein from the American lobster, Homarus americanus, with glutathione. Arch Biochem Biophys. 1991 Oct;290(1):207–213. doi: 10.1016/0003-9861(91)90610-u. [DOI] [PubMed] [Google Scholar]
  4. Brouwer M., Winge D. R., Gray W. R. Structural and functional diversity of copper-metallothioneins from the American lobster Homarus americanus. J Inorg Biochem. 1989 Apr;35(4):289–303. doi: 10.1016/0162-0134(89)84018-8. [DOI] [PubMed] [Google Scholar]
  5. Casterline J. L., Jr, Yip G. The distribution and binding of cadmium in oyster, soybean, and rat liver and kidney. Arch Environ Contam Toxicol. 1975;3(3):319–329. doi: 10.1007/BF02220744. [DOI] [PubMed] [Google Scholar]
  6. Churchich J. E., Scholz G., Kwok F. Activation of pyridoxal kinase by metallothionein. Biochim Biophys Acta. 1989 Jul 6;996(3):181–186. doi: 10.1016/0167-4838(89)90245-8. [DOI] [PubMed] [Google Scholar]
  7. Feldman S. L., Squibb K. S., Cousins R. J. Degradation of cadmium-thionein in rat liver and kidney. J Toxicol Environ Health. 1978 Sep-Nov;4(5-6):805–813. doi: 10.1080/15287397809529701. [DOI] [PubMed] [Google Scholar]
  8. Fowler B. A., Hildebrand C. E., Kojima Y., Webb M. Nomenclature of metallothionein. Experientia Suppl. 1987;52:19–22. doi: 10.1007/978-3-0348-6784-9_2. [DOI] [PubMed] [Google Scholar]
  9. Gick G. G., McCarty K. S., Sr Amplification of the metallothionein-I gene in cadmium- and zinc-resistant Chinese hamster ovary cells. J Biol Chem. 1982 Aug 10;257(15):9049–9053. [PubMed] [Google Scholar]
  10. Hamer D. H., Thiele D. J., Lemontt J. E. Function and autoregulation of yeast copperthionein. Science. 1985 May 10;228(4700):685–690. doi: 10.1126/science.3887570. [DOI] [PubMed] [Google Scholar]
  11. Harlow P., Watkins E., Thornton R. D., Nemer M. Structure of an ectodermally expressed sea urchin metallothionein gene and characterization of its metal-responsive region. Mol Cell Biol. 1989 Dec;9(12):5445–5455. doi: 10.1128/mcb.9.12.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hildebrand C. E., Tobey R. A., Campbell E. W., Enger M. D. A cadmium-resistant variant of the Chinese hamster (CHO) cell with increased metallothionein induction capacity. Exp Cell Res. 1979 Dec;124(2):237–246. doi: 10.1016/0014-4827(79)90199-x. [DOI] [PubMed] [Google Scholar]
  13. Imbert J., Zafarullah M., Culotta V. C., Gedamu L., Hamer D. Transcription factor MBF-I interacts with metal regulatory elements of higher eucaryotic metallothionein genes. Mol Cell Biol. 1989 Dec;9(12):5315–5323. doi: 10.1128/mcb.9.12.5315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jackson R. J. Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell. 1993 Jul 16;74(1):9–14. doi: 10.1016/0092-8674(93)90290-7. [DOI] [PubMed] [Google Scholar]
  15. KAGI J. H., VALEE B. L. Metallothionein: a cadmium- and zinc-containing protein from equine renal cortex. J Biol Chem. 1960 Dec;235:3460–3465. [PubMed] [Google Scholar]
  16. Kägi J. H., Kojima Y. Chemistry and biochemistry of metallothionein. Experientia Suppl. 1987;52:25–61. doi: 10.1007/978-3-0348-6784-9_3. [DOI] [PubMed] [Google Scholar]
  17. Leber A. P., Miya T. S. A mechanism for cadmium- and zinc-induced tolerance to cadmium toxicity: involvement of metallothionein. Toxicol Appl Pharmacol. 1976 Sep;37(3):403–414. doi: 10.1016/0041-008x(76)90202-7. [DOI] [PubMed] [Google Scholar]
  18. Nemer M., Thornton R. D., Stuebing E. W., Harlow P. Structure, spatial, and temporal expression of two sea urchin metallothionein genes, SpMTB1 and SpMTA. J Biol Chem. 1991 Apr 5;266(10):6586–6593. [PubMed] [Google Scholar]
  19. Nemer M., Travaglini E. C., Rondinelli E., D'Alonzo J. Developmental regulation, induction, and embryonic tissue specificity of sea urchin metallothionein gene expression. Dev Biol. 1984 Apr;102(2):471–482. doi: 10.1016/0012-1606(84)90212-4. [DOI] [PubMed] [Google Scholar]
  20. Nemer M., Wilkinson D. G., Travaglini E. C., Sternberg E. J., Butt T. R. Sea urchin metallothionein sequence: key to an evolutionary diversity. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4992–4994. doi: 10.1073/pnas.82.15.4992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Olsson P. E., Hogstrand C. Improved separation of perch liver metallothionein by fast protein liquid chromatography. J Chromatogr. 1987 Jul 31;402:293–299. doi: 10.1016/0021-9673(87)80027-4. [DOI] [PubMed] [Google Scholar]
  22. Olsson P. E., Hyllner S. J., Zafarullah M., Andersson T., Gedamu L. Differences in metallothionein gene expression in primary cultures of rainbow trout hepatocytes and the RTH-149 cell line. Biochim Biophys Acta. 1990 May 24;1049(1):78–82. doi: 10.1016/0167-4781(90)90086-h. [DOI] [PubMed] [Google Scholar]
  23. Olsson P. E., Zafarullah M., Foster R., Hamor T., Gedamu L. Developmental regulation of metallothionein mRNA, zinc and copper levels in rainbow trout, Salmo gairdneri. Eur J Biochem. 1990 Oct 5;193(1):229–235. doi: 10.1111/j.1432-1033.1990.tb19327.x. [DOI] [PubMed] [Google Scholar]
  24. Otto E., Allen J. M., Young J. E., Palmiter R. D., Maroni G. A DNA segment controlling metal-regulated expression of the Drosophila melanogaster metallothionein gene Mtn. Mol Cell Biol. 1987 May;7(5):1710–1715. doi: 10.1128/mcb.7.5.1710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Palmiter R. D. Regulation of metallothionein genes by heavy metals appears to be mediated by a zinc-sensitive inhibitor that interacts with a constitutively active transcription factor, MTF-1. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1219–1223. doi: 10.1073/pnas.91.4.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roesijadi G., Kielland S., Klerks P. Purification and properties of novel molluscan metallothioneins. Arch Biochem Biophys. 1989 Sep;273(2):403–413. doi: 10.1016/0003-9861(89)90499-2. [DOI] [PubMed] [Google Scholar]
  27. Roesijadi G., Vestling M. M., Murphy C. M., Klerks P. L., Fenselau C. C. Structure and time-dependent behavior of acetylated and non-acetylated forms of a molluscan metallothionein. Biochim Biophys Acta. 1991 Jul 8;1074(2):230–236. doi: 10.1016/0304-4165(91)90157-c. [DOI] [PubMed] [Google Scholar]
  28. Theodore L., Ho A. S., Maroni G. Recent evolutionary history of the metallothionein gene Mtn in Drosophila. Genet Res. 1991 Dec;58(3):203–210. doi: 10.1017/s0016672300029955. [DOI] [PubMed] [Google Scholar]
  29. Thiele D. J. Metal-regulated transcription in eukaryotes. Nucleic Acids Res. 1992 Mar 25;20(6):1183–1191. doi: 10.1093/nar/20.6.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thiele D. J., Walling M. J., Hamer D. H. Mammalian metallothionein is functional in yeast. Science. 1986 Feb 21;231(4740):854–856. doi: 10.1126/science.3080806. [DOI] [PubMed] [Google Scholar]
  31. Udom A. O., Brady F. O. Reactivation in vitro of zinc-requiring apo-enzymes by rat liver zinc-thionein. Biochem J. 1980 May 1;187(2):329–335. doi: 10.1042/bj1870329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Unger M. E., Chen T. T., Murphy C. M., Vestling M. M., Fenselau C., Roesijadi G. Primary structure of molluscan metallothioneins deduced from PCR-amplified cDNA and mass spectrometry of purified proteins. Biochim Biophys Acta. 1991 Aug 6;1074(3):371–377. doi: 10.1016/0304-4165(91)90087-w. [DOI] [PubMed] [Google Scholar]
  33. Wilkinson D. G., Nemer M. Metallothionein genes MTa and MTb expressed under distinct quantitative and tissue-specific regulation in sea urchin embryos. Mol Cell Biol. 1987 Jan;7(1):48–58. doi: 10.1128/mcb.7.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zafarullah M., Bonham K., Gedamu L. Structure of the rainbow trout metallothionein B gene and characterization of its metal-responsive region. Mol Cell Biol. 1988 Oct;8(10):4469–4476. doi: 10.1128/mcb.8.10.4469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Zafarullah M., Olsson P. E., Gedamu L. Endogenous and heavy-metal-ion-induced metallothionein gene expression in salmonid tissues and cell lines. Gene. 1989 Nov 15;83(1):85–93. doi: 10.1016/0378-1119(89)90406-x. [DOI] [PubMed] [Google Scholar]
  36. Zeng J., Heuchel R., Schaffner W., Kägi J. H. Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1. FEBS Lett. 1991 Feb 25;279(2):310–312. doi: 10.1016/0014-5793(91)80175-3. [DOI] [PubMed] [Google Scholar]
  37. Zeng J., Vallee B. L., Kägi J. H. Zinc transfer from transcription factor IIIA fingers to thionein clusters. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9984–9988. doi: 10.1073/pnas.88.22.9984. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES