Abstract
Metallothionein (MT) is a metal-binding protein rapidly accreted in many tissues in response to trace elements or hormones. To gain an understanding of the regulation of MT accretion, rates of MT synthesis and degradation were determined by using a decay-kinetics technique. A chicken macrophage-cell line (HD11) that rapidly accretes incremental amounts of MT when stimulated with increasing concentrations of Zn2+ or Cd2+ was studied. The maximum rate of MT accretion occurred at 50 microM-Zn2+ or 20 microM-Cd2+. The absolute rate of MT accretion was less in macrophages incubated with 25 microM- as compared with 50 microM-Zn2+, owing to decreased and increased rates of MT synthesis and degradation respectively. The absolute rate of MT accretion was less in macrophages incubated with 10 microM- as compared with 20 microM-Cd2+, owing to a decreased rate of MT synthesis with no change in degradation. Compared with macrophages continually incubated with 50 microM-Zn2+, removal of Zn2+ from medium previously containing 50 microM-Zn2+ decreased the absolute rate of MT accretion, owing to decreased and increased rates of MT synthesis and degradation respectively. Removal of Cd2+ from medium previously containing 20 microM-Cd2+ also decreased the absolute rate of MT accretion in macrophages. Unlike Zn2+ removal, the decrease in MT accretion was due to a decreased rate of MT synthesis with no change in degradation. When macrophages incubated with 50 microM-Zn2+ were subsequently incubated with 20 microM-Cd2+, rates of MT synthesis and accretion were decreased as compared with cells continually incubated with 50 microM-Zn2+ or 20 microM-Cd2+. When macrophages incubated with 20 microM-Cd2+ were subsequently incubated with 50 microM-Zn2+, rates of MT synthesis and accretion were increased as compared with cells continually incubated with 50 microM-Zn2+ or 20 microM-Cd2+. Switching the metal in the incubation medium did not influence the rate of MT degradation. Our results indicate that the rate of MT accretion is determined by variations in the rates of MT synthesis and degradation, depending upon the inducing metal and the concentration of the metal.
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- Beug H., von Kirchbach A., Döderlein G., Conscience J. F., Graf T. Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation. Cell. 1979 Oct;18(2):375–390. doi: 10.1016/0092-8674(79)90057-6. [DOI] [PubMed] [Google Scholar]
- Bremner I., Hoekstra G., Davies N. T., Young B. W. Effect of zinc status of rats on the synthesis and degradation of copper-induced metallothioneins. Biochem J. 1978 Sep 15;174(3):883–892. doi: 10.1042/bj1740883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cain K., Holt D. E. Metallothionein degradation: metal composition as a controlling factor. Chem Biol Interact. 1979;28(1):91–106. doi: 10.1016/0009-2797(79)90117-0. [DOI] [PubMed] [Google Scholar]
- Chen M. L., Failla M. L. Degradation of zinc-metallothionein in monolayer cultures of rat hepatocytes. Proc Soc Exp Biol Med. 1989 Jun;191(2):130–138. doi: 10.3181/00379727-191-42898. [DOI] [PubMed] [Google Scholar]
- Cousins R. J., Dunn M. A., Leinart A. S., Yedinak K. C., DiSilvestro R. A. Coordinate regulation of zinc metabolism and metallothionein gene expression in rats. Am J Physiol. 1986 Dec;251(6 Pt 1):E688–E694. doi: 10.1152/ajpendo.1986.251.6.E688. [DOI] [PubMed] [Google Scholar]
- Durnam D. M., Palmiter R. D. Transcriptional regulation of the mouse metallothionein-I gene by heavy metals. J Biol Chem. 1981 Jun 10;256(11):5712–5716. [PubMed] [Google Scholar]
- Etzel K. R., Cousins R. J. Hormonal regulation of liver metallothionein zinc: independent and synergistic action of glucagon and glucocorticoids. Proc Soc Exp Biol Med. 1981 Jun;167(2):233–236. doi: 10.3181/00379727-167-41155. [DOI] [PubMed] [Google Scholar]
- Feldman S. L., Cousins R. J. Degradation of hepatic zinc-thionein after parenteral zinc administration. Biochem J. 1976 Dec 15;160(3):583–588. doi: 10.1042/bj1600583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Fernando L. P., Wei D. Y., Andrews G. K. Structure and expression of chicken metallothionein. J Nutr. 1989 Feb;119(2):309–318. doi: 10.1093/jn/119.2.309. [DOI] [PubMed] [Google Scholar]
- Hager L. J., Palmiter R. D. Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids. Nature. 1981 May 28;291(5813):340–342. doi: 10.1038/291340a0. [DOI] [PubMed] [Google Scholar]
- Huang I. Y., Yoshida A. Mouse liver metallothioneins. Complete amino acid sequence of metallothionein-I. J Biol Chem. 1977 Nov 25;252(22):8217–8221. [PubMed] [Google Scholar]
- Hunziker P. E., Kägi J. H. Isolation and characterization of six human hepatic isometallothioneins. Biochem J. 1985 Oct 15;231(2):375–382. doi: 10.1042/bj2310375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karin M., Slater E. P., Herschman H. R. Regulation of metallothionein synthesis in HeLa cells by heavy metals and glucocorticoids. J Cell Physiol. 1981 Jan;106(1):63–74. doi: 10.1002/jcp.1041060108. [DOI] [PubMed] [Google Scholar]
- Kobayashi S., Imano M., Kimura M. Induction and degradation of Zn-, Cu- and Cd-thionein in Chang liver cells. Chem Biol Interact. 1985 Jan;52(3):319–334. doi: 10.1016/0009-2797(85)90027-4. [DOI] [PubMed] [Google Scholar]
- Koizumi S., Otaki N., Kimura M. Estimation of thionein synthesis in cultured cells by slab gel electrophoresis. Ind Health. 1982;20(2):101–108. doi: 10.2486/indhealth.20.101. [DOI] [PubMed] [Google Scholar]
- Lin L. Y., McCormick C. C. Quantitation of chick tissue zinc-metallothionein by gel electrophoresis and silver stain enhancement. Comp Biochem Physiol C. 1986;85(1):75–84. doi: 10.1016/0742-8413(86)90054-x. [DOI] [PubMed] [Google Scholar]
- McCormick C. C., Fullmer C. S., Garvey J. S. Amino acid sequence and comparative antigenicity of chicken metallothionein. Proc Natl Acad Sci U S A. 1988 Jan;85(2):309–313. doi: 10.1073/pnas.85.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCormick C. C. Induction and accumulation of metallothionein in liver and pancreas of chicks given oral zinc: a tissue comparison. J Nutr. 1984 Jan;114(1):191–203. doi: 10.1093/jn/114.1.191. [DOI] [PubMed] [Google Scholar]
- McCormick C. C., Menard M. P., Cousins R. J. Induction of hepatic metallothionein by feeding zinc to rats of depleted zinc status. Am J Physiol. 1981 Apr;240(4):E414–E421. doi: 10.1152/ajpendo.1981.240.4.E414. [DOI] [PubMed] [Google Scholar]
- Mehra R. K., Bremner I. Studies on the metabolism of rat liver copper-metallothionein. Biochem J. 1985 May 1;227(3):903–908. doi: 10.1042/bj2270903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monia B. P., Butt T. R., Ecker D. J., Mirabelli C. K., Crooke S. T. Metallothionein turnover in mammalian cells. Implications in metal toxicity. J Biol Chem. 1986 Aug 25;261(24):10957–10959. [PubMed] [Google Scholar]
- 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]
- Onosaka S., Cherian M. G. The induced synthesis of metallothionein in various tissues of rat in response to metals. I. Effect of repeated injection of cadmium salts. Toxicology. 1981;22(2):91–101. doi: 10.1016/0300-483x(81)90109-8. [DOI] [PubMed] [Google Scholar]
- Prins H. W., Van den Hamer C. J. Degradation of 35S-labeled metallothionein in the liver and the kidney of brindled mice: model for Menkes' disease. Life Sci. 1981 Jun 29;28(26):2953–2959. doi: 10.1016/0024-3205(81)90272-1. [DOI] [PubMed] [Google Scholar]
- Richards M. P., Steele N. C. Isolation and quantitation of metallothionein isoforms using reversed-phase high-performance liquid chromatography. J Chromatogr. 1987 Jul 31;402:243–256. doi: 10.1016/0021-9673(87)80022-5. [DOI] [PubMed] [Google Scholar]
- Squibb K. S., Cousins R. J., Feldman S. L. Control of zinc-thionein synthesis in rat liver. Biochem J. 1977 Apr 15;164(1):223–228. doi: 10.1042/bj1640223. [DOI] [PMC free article] [PubMed] [Google Scholar]