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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(4):1259–1262. doi: 10.1073/pnas.87.4.1259

Erythrocyte metallothionein as an index of zinc status in humans.

A Grider 1, L B Bailey 1, R J Cousins 1
PMCID: PMC53453  PMID: 2304897

Abstract

Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet (0.7 mg of zinc per kg of diet) for an 8-day depletion period after 3 days of acclimation. Fasting plasma zinc concentrations were reduced approximately 7%. Metallothionein in the erythrocyte lysates was significantly decreased to 59% of the initial level by the end of the depletion period. Supplementation of these depleted subjects with zinc (50 mg) did not increase erythrocyte metallothionein levels within 24 hr. Daily supplementation of control subjects with zinc (50 mg/day) increased erythrocyte metallothionein to a 7-fold maximum within 7 days. These levels were reduced by 61% within 14 days after zinc supplementation was terminated. Incubation of rat [35S]metallothionein with human erythrocyte lysate showed a time-dependent increase in 35S soluble in 20% trichloroacetic acid, indicating degradation of the labeled protein, presumably via protease activity in the lysate. It is proposed that zinc supplementation induces erythrocyte metallothionein during erythropoiesis and that low zinc intake decreases synthesis and/or accelerates degradation of the protein in reticulocytes/erythrocytes. Metallothionein levels in erythrocytes may provide a useful index upon which to assess zinc status in humans.

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Selected References

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

  1. Abel J., de Ruiter N. Inhibition of hydroxyl-radical-generated DNA degradation by metallothionein. Toxicol Lett. 1989 May;47(2):191–196. doi: 10.1016/0378-4274(89)90075-1. [DOI] [PubMed] [Google Scholar]
  2. Blalock T. L., Dunn M. A., Cousins R. J. Metallothionein gene expression in rats: tissue-specific regulation by dietary copper and zinc. J Nutr. 1988 Feb;118(2):222–228. doi: 10.1093/jn/118.2.222. [DOI] [PubMed] [Google Scholar]
  3. Bremner I., Morrison J. N., Wood A. M., Arthur J. R. Effects of changes in dietary zinc, copper and selenium supply and of endotoxin administration on metallothionein I concentrations in blood cells and urine in the rat. J Nutr. 1987 Sep;117(9):1595–1602. doi: 10.1093/jn/117.9.1595. [DOI] [PubMed] [Google Scholar]
  4. Chung J., Nartey N. O., Cherian M. G. Metallothionein levels in liver and kidney of Canadians--a potential indicator of environmental exposure to cadmium. Arch Environ Health. 1986 Sep-Oct;41(5):319–323. doi: 10.1080/00039896.1986.9936704. [DOI] [PubMed] [Google Scholar]
  5. Cousins R. J. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev. 1985 Apr;65(2):238–309. doi: 10.1152/physrev.1985.65.2.238. [DOI] [PubMed] [Google Scholar]
  6. Cousins R. J., Leinart A. S. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J. 1988 Oct;2(13):2884–2890. doi: 10.1096/fasebj.2.13.2458983. [DOI] [PubMed] [Google Scholar]
  7. Davies K. J., Goldberg A. L. Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cells. J Biol Chem. 1987 Jun 15;262(17):8227–8234. [PubMed] [Google Scholar]
  8. Dunn M. A., Cousins R. J. Kinetics of zinc metabolism in the rat: effect of dibutyryl cAMP. Am J Physiol. 1989 Mar;256(3 Pt 1):E420–E430. doi: 10.1152/ajpendo.1989.256.3.E420. [DOI] [PubMed] [Google Scholar]
  9. Feldman S. L., Failla M. L., Cousins R. J. Degradation of rat liver metallothioneins in vitro. Biochim Biophys Acta. 1978 Dec 18;544(3):638–646. doi: 10.1016/0304-4165(78)90338-0. [DOI] [PubMed] [Google Scholar]
  10. Gordon P. R., Woodruff C. W., Anderson H. L., O'Dell B. L. Effect of acute zinc deprivation on plasma zinc and platelet aggregation in adult males. Am J Clin Nutr. 1982 Jan;35(1):113–119. doi: 10.1093/ajcn/35.1.113. [DOI] [PubMed] [Google Scholar]
  11. Grider A., Kao K. J., Klein P. A., Cousins R. J. Enzyme-linked immunosorbent assay for human metallothionein: correlation of induction with infection. J Lab Clin Med. 1989 Feb;113(2):221–228. [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Miles L. E., Lipschitz D. A., Bieber C. P., Cook J. D. Measurement of serum ferritin by a 2-site immunoradiometric assay. Anal Biochem. 1974 Sep;61(1):209–224. doi: 10.1016/0003-2697(74)90347-9. [DOI] [PubMed] [Google Scholar]
  14. Morishita K., Parker D. S., Mucenski M. L., Jenkins N. A., Copeland N. G., Ihle J. N. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Cell. 1988 Sep 9;54(6):831–840. doi: 10.1016/s0092-8674(88)91175-0. [DOI] [PubMed] [Google Scholar]
  15. Onosaka S., Min K. S., Fukuhara C., Tanaka K., Tashiro S., Shimizu I., Furuta M., Yasutomi T., Kobashi K., Yamamoto K. Concentrations of metallothionein and metals in malignant and non-malignant tissues in human liver. Toxicology. 1986 Mar;38(3):261–268. doi: 10.1016/0300-483x(86)90142-3. [DOI] [PubMed] [Google Scholar]
  16. Robertson A., Morrison J. N., Wood A. M., Bremner I. Effects of iron deficiency on metallothionein-I concentrations in blood and tissues of rats. J Nutr. 1989 Mar;119(3):439–445. doi: 10.1093/jn/119.3.439. [DOI] [PubMed] [Google Scholar]
  17. Rote K., Rogers S., Pratt G., Rechsteiner M. Degradation of structurally characterized proteins injected into HeLa cells. Comparison with their stability in rabbit reticulocyte lysate. J Biol Chem. 1989 Jun 15;264(17):9772–9779. [PubMed] [Google Scholar]
  18. Sato M., Mehra R. K., Bremner I. Measurement of plasma metallothionein-I in the assessment of the zinc status of zinc-deficient and stressed rats. J Nutr. 1984 Sep;114(9):1683–1689. doi: 10.1093/jn/114.9.1683. [DOI] [PubMed] [Google Scholar]
  19. Thomas J. P., Bachowski G. J., Girotti A. W. Inhibition of cell membrane lipid peroxidation by cadmium- and zinc-metallothioneins. Biochim Biophys Acta. 1986 Dec 10;884(3):448–461. doi: 10.1016/0304-4165(86)90195-9. [DOI] [PubMed] [Google Scholar]
  20. Thornalley P. J., Vasák M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta. 1985 Jan 21;827(1):36–44. doi: 10.1016/0167-4838(85)90098-6. [DOI] [PubMed] [Google Scholar]
  21. Torrubia J. O., Garay R. Evidence for a major route for zinc uptake in human red blood cells: [Zn(HCO3)2Cl]- influx through the [Cl-/HCO3-] anion exchanger. J Cell Physiol. 1989 Feb;138(2):316–322. doi: 10.1002/jcp.1041380214. [DOI] [PubMed] [Google Scholar]
  22. Turnlund J. R., King J. C., Keyes W. R., Gong B., Michel M. C. A stable isotope study of zinc absorption in young men: effects of phytate and alpha-cellulose. Am J Clin Nutr. 1984 Nov;40(5):1071–1077. doi: 10.1093/ajcn/40.5.1071. [DOI] [PubMed] [Google Scholar]

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