Metallothionein as a Trap for Reactive Organic Intermediates

  • Curtis D. Klaassen
  • Stuart Z. Cagen
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Metallothionein is a cadmium-binding protein first isolated from equine renal cortex by Margoshes and Vallee (1957). It is a protein of low molecular weight (about 6,000) having a very high cysteine content (about 30% of the amino acid residues) and an absence of aromatic amino acids and histidine (Kagi et al., 1974). Similar proteins have been isolated from the liver and/or kidney of humans (Pulido et al., 1966; Buhler and Kagi, 1974), and many other species. The amino acid sequences of equine renal metallothionein (Kojima et al., 1976) and hepatic metallothionein from mice (Huange et al., 1977) have been determined. The metallothionein from these two sources both contain 20 cysteine residues (out of a total of 61 amino acid residues) and remarkable structural homology in the amino acid sequence.

Keywords

Liver Homogenate Zinc Chloride High Molecular Weight Protein Mercapturic Acid Diethyl Maleate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Buhler, R.H., and Kagi, J.H.R., 1974, Human hepatic metallothionein, FEBS Lett., 39: 229–234.PubMedCrossRefGoogle Scholar
  2. Bremner, I., and Davies, N.T., 1975, Induction of metallothionein in rat liver by zinc injection and restriction of food intake, Biochem. J., 149: 733–738.PubMedGoogle Scholar
  3. Cagen, S.Z., and Klaassen, C.D., 1979, Protection of carbon tetrachloride (CC14)-induced hepatotoxicity by zinc: Role of metallothionein, Toxicol. Appl. Pharmacol., 51: 107–116.PubMedCrossRefGoogle Scholar
  4. Cagen, S.7., and Klaassen, C.D., 1980, Binding of glutathionedepleting agents to metallothionein, Toxicol. Appl. Pharmacol., 54: 229–237.CrossRefGoogle Scholar
  5. Chasseaud, L.F., 1973, The nature and distribution of enzymes catalyzing the conjugation of glutathione with foreign compounds, Drug Met. Rev. 2, 185–220.Google Scholar
  6. Chvapil, M., Ludwig, J.C., Sipes, I.G., and Misiorowski, R.L., 1976, Inhibition of NADPH oxidation and related drug oxidation in liver microsomes by zinc, Biochem. Pharmacol. 125: 1787–1791.CrossRefGoogle Scholar
  7. Ellman, G.L., 1959, Tissue sulfhydryl groups, Arch. Biochem. Biophys., 82: 70–77, 1959.Google Scholar
  8. Evans, G.W., 1973, Copper homeostasis in the mammalian system, Physiol. Rev., 53: 535–570.PubMedGoogle Scholar
  9. Gillette, J.R., 1977, Formation of reactive metabolites of foreign compounds and their covalent binding to cellular constituents, in: “Handbook of Physiology: Reactions to Environmental Agents,” D.H.K. Lee, ed., Section 9, Chapter 37, pp. 577–589, American Physiological Society, Bethesda, MD.Google Scholar
  10. Huang, I.-Y., Yoshida, A., Tsundo, H., and Nakagima, H., 1977, Mouse liver metallothioneins. Complete amino acid sequence, J. Biol. Chem., 252: 8217–8221.PubMedGoogle Scholar
  11. Kagi, J.H.R., Himmelhoch, S.R., Whanger, P.D., Bethue, J.D., and Vallee, B.L., 1974, Equine hepatic and renal metallothionein. Purification, molecular weight, amino acid composition and metal content. J. Biol. Chem. 249: 3537–3542.PubMedGoogle Scholar
  12. Kagi, J.H.R., and Vallee, B.L., 1960, Metallothionein: A cadmium and zinc-containing protein from equine renal cortex, J. Biol. Chem. 235: 3460–3465.PubMedGoogle Scholar
  13. Kagi, J.H.R., and Vallee, B.L., 1961, Metallothionein: A cadmium and zinc-containing protein from equine renal cortex, II. Physiochemical properties, J. Biol. Chem. 236: 2435–2442.PubMedGoogle Scholar
  14. Kimura, M., Otaki, N., Yoshiki, S., Suzuki, M., Horiuchi, N., and Studa, T., 1974, The isolation of metallothionein and its protective role in cadmium poisoning. Arch. Biochem. Biophys., 165: 340–348.PubMedCrossRefGoogle Scholar
  15. Kojima, Y., Berger, C., Vallee, B.L., and Kagi, J.H.R., 1976, Amino-acid sequence of equine renal metallothionein 18, Proc. Natl. Acad. Sci., U.S.A., 73: 3413–3417.PubMedCrossRefGoogle Scholar
  16. Kotsonis, F.N., and Klaassen, C.D., 1977, Comparison of methods for estimating hepatic metallothionein in rats, Toxicol. Appl. Pharmacol., 42: 583–588.PubMedCrossRefGoogle Scholar
  17. Kotsonis, F.N. and Klaassen, C.D., 1979, Increase in hepatic metallothionein in rats treated with alkylating agents, Toxicol. Appl. Pharmacol., 51: 19–27.PubMedCrossRefGoogle Scholar
  18. Leber, A.P., and Miya, T.S., 1976, A mechanism for cadmium-and zinc-induced tolerance to cadmium toxicity: Involvement of metallothionein. Toxicol. Appl. Pharmacol. 47: 403–414.CrossRefGoogle Scholar
  19. Margoshes, M., and Vallee, B.T., 1957, A cadmium protein from equine kidney cortex, J. Amer. Chem. Soc., 79: 4813–4814.CrossRefGoogle Scholar
  20. Nordberg, G.F., 1971, Effects of acute and chronic cadmium exposure on the testicles of mice. With special reference to protective effects of metallothionein, Environ. Physiol., 1: 171–187.Google Scholar
  21. Oh, S.H., Deagen, J.T., Whanger, P.D., and Weswig, P.H., 1978, Biological function of metallothionein. V. Its induction in rats by various stresses. Am. J. Physiol. 234: E287 - E285.Google Scholar
  22. Piotrowski, J.K., Bolanowska, W., and Sapota, A., 1973, Evaluation of metallothionein content in animal tissues, Acta Biochem. Pol., 20: 207–215.Google Scholar
  23. Piscator, M., 1964, On cadmium in normal human kidney together with a report on the isolation of metallothionein from livers of cadmium exposed rabbits. Nord. Hyq. Tisdkr., 45: 76–82.Google Scholar
  24. Probst, G.S., Bousquet, W.F., and Miya, T.S., 1977, Correlation of hepatic metallothionein concentration with acute cadmium toxicity in the mouse. Toxicol. Appl. Pharmacol. 39: 61–69.PubMedCrossRefGoogle Scholar
  25. Pulido, P., Kagi, J.H.R., and Vallee, B.L., 1966, Isolation and some properties of human metallothionein, Biochemistry 5: 1768–1777.PubMedCrossRefGoogle Scholar
  26. Richards, M.P., and Cousins, R.J., 1975, Mammalian zinc homeostasis: Requirement for RNA and metallothionein synthesis, Biochem. Biophys. Res. Commun., 64: 1215–1223.PubMedCrossRefGoogle Scholar
  27. Shaikh, Z.A., and Smith, J.C., 1976, The biosynthesis of metallothionein in rat liver and kidney after administration of cadmium, Chem. Biol. Interact. 15: 327–336.PubMedCrossRefGoogle Scholar
  28. Sobocinski, P.7., Canterbury, W.J., Jr., Mapes, C.A., and Dinterman, R.E., 1978, Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection, Am. J. Physiol., 243: E399 - E406.Google Scholar
  29. Squibb, K.S., Cousins, R.J., and Feldman, S.L., 1977, Control of zinc-thionein synthesis in rat liver, Biochem. J., 164: 223228.Google Scholar
  30. Webb, M., 1972, Binding of cadmium ions by rat liver and kidney, Biochem. Pharmacol., 21: 2751–2765.PubMedCrossRefGoogle Scholar
  31. Weser, V., Rupp, H., Donay, F., Linnemann, F., Voelter, W., Voetsch, W., and Jung, G., 1973, Characterization of Cd, Zn-thionein isolated from rat and chicken liver, Eur. J. Biochem. 39:127–140..Google Scholar
  32. Winge, D.R., Premakumar, R., and Rajogopalan, K.V., 1975, Metal-induced formation of metallothionein in rat liver, Arch. Biochem. Biophys., 170: 242–252.PubMedCrossRefGoogle Scholar
  33. Winge, D.R., and Rajagopalan, K.V., 1972, Purification and some properties of cadmium-binding protein from rat liver, Arch. Biochem. Biophys., 153: 755–762.PubMedCrossRefGoogle Scholar
  34. Wood, J.L., 1970, Biochemistry of mercapturic acid formation, in: “Metabolic Conjugation and Metabolic Hydrolysis,” W.H. Fishman, ed., Volume 2, pp. 261–299, Academic Press, NY.CrossRefGoogle Scholar
  35. Yau, E.T., and Mennear, J.H., 1977, Pancreatic metallothionein: Protection against cadmium-induced inhibition of insulin secretory activity, Toxicol. Appl. fharmacol., 39: 515–520.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Curtis D. Klaassen
    • 1
  • Stuart Z. Cagen
    • 1
  1. 1.Department of PharmacologyUniversity of Kansas Medical CenterKansas CityUSA

Personalised recommendations