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. 1987 Feb;7(2):600–605. doi: 10.1128/mcb.7.2.600

Transient response of amplified metallothionein genes in CHO cells to induction by alpha interferon.

S Morris, P C Huang
PMCID: PMC365114  PMID: 3821725

Abstract

Alpha interferon treatment of CHO cells elicits the rapid synthesis of many gene products, including metallothionein (MT), a protein which avidly binds heavy metals such as zinc, cadmium, and copper. Since MTs appear to have a pleiotropic role in the cell, ranging from metal detoxification to free-radical scavenging, interferon treatment may trigger a generalized defense mechanism. Activation by interferon, however, was transient, with MT mRNA being maximally detectable by a cytodot procedure within the first hour. Subsequent addition of interferon was ineffective until 7 h after the initial treatment. The action of zinc, a potent inducer of MT, however, remained independent of alpha interferon induction. The transient nature of induction by interferon was examined for altered rate of MT mRNA turnover.

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Selected References

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

  1. Anderson P., Yip Y. K., Vilcek J. Specific binding of 125I-human interferon-gamma to high affinity receptors on human fibroblasts. J Biol Chem. 1982 Oct 10;257(19):11301–11304. [PubMed] [Google Scholar]
  2. Bakka A., Johnsen A. S., Endresen L., Rugstad H. E. Radioresistance in cells with high content of metallothionein. Experientia. 1982 Mar 15;38(3):381–383. doi: 10.1007/BF01949406. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Branca A. A., Faltynek C. R., D'Alessandro S. B., Baglioni C. Interaction of interferon with cellular receptors. Internalization and degradation of cell-bound interferon. J Biol Chem. 1982 Nov 25;257(22):13291–13296. [PubMed] [Google Scholar]
  5. Carter A. D., Felber B. K., Walling M. J., Jubier M. F., Schmidt C. J., Hamer D. H. Duplicated heavy metal control sequences of the mouse metallothionein-I gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7392–7396. doi: 10.1073/pnas.81.23.7392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colonno R. J. Accumulation of newly synthesized mRNAs in response to human fibroblast (beta) interferon. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4763–4766. doi: 10.1073/pnas.78.8.4763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colonno R. J., Pang R. H. Induction of unique mRNAs by human interferons. J Biol Chem. 1982 Aug 25;257(16):9234–9237. [PubMed] [Google Scholar]
  8. Cowan N. J., Dobner P. R., Fuchs E. V., Cleveland D. W. Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions. Mol Cell Biol. 1983 Oct;3(10):1738–1745. doi: 10.1128/mcb.3.10.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Durnam D. M., Hoffman J. S., Quaife C. J., Benditt E. P., Chen H. Y., Brinster R. L., Palmiter R. D. Induction of mouse metallothionein-I mRNA by bacterial endotoxin is independent of metals and glucocorticoid hormones. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1053–1056. doi: 10.1073/pnas.81.4.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  12. Friedman R. L., Stark G. R. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature. 1985 Apr 18;314(6012):637–639. doi: 10.1038/314637a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Griffith J. K. Coordinate expression of amplified metallothionein I and II genes in cadmium-resistant Chinese hamster cells. Mol Cell Biol. 1985 Dec;5(12):3525–3531. doi: 10.1128/mcb.5.12.3525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Johnston R. B., Jr, Lehmeyer J. E. Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J Clin Invest. 1976 Apr;57(4):836–841. doi: 10.1172/JCI108359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karin M., Cathala G., Nguyen-Huu M. C. Expression and regulation of a human metallothionein gene carried on an autonomously replicating shuttle vector. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4040–4044. doi: 10.1073/pnas.80.13.4040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  19. Karin M. Metallothioneins: proteins in search of function. Cell. 1985 May;41(1):9–10. doi: 10.1016/0092-8674(85)90051-0. [DOI] [PubMed] [Google Scholar]
  20. Larner A. C., Chaudhuri A., Darnell J. E., Jr Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction. J Biol Chem. 1986 Jan 5;261(1):453–459. [PubMed] [Google Scholar]
  21. Lengyel P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982;51:251–282. doi: 10.1146/annurev.bi.51.070182.001343. [DOI] [PubMed] [Google Scholar]
  22. Marzluff W. F., Jr, Murphy E. C., Jr, Huang R. C. Transcription of ribonucleic acid in isolated mouse myeloma nuclei. Biochemistry. 1973 Aug 28;12(18):3440–3446. doi: 10.1021/bi00742a013. [DOI] [PubMed] [Google Scholar]
  23. Olafson R. W., Sim R. G. An electrochemical approach to quantitation and characterization of metallothioneins. Anal Biochem. 1979 Dec;100(2):343–351. doi: 10.1016/0003-2697(79)90239-2. [DOI] [PubMed] [Google Scholar]
  24. Pine R., Cismowski M., Liu S. W., Huang P. C. Construction and characterization of a library of metallothionein coding sequence mutants. DNA. 1985 Apr;4(2):115–126. doi: 10.1089/dna.1985.4.115. [DOI] [PubMed] [Google Scholar]
  25. Richards R. I., Heguy A., Karin M. Structural and functional analysis of the human metallothionein-IA gene: differential induction by metal ions and glucocorticoids. Cell. 1984 May;37(1):263–272. doi: 10.1016/0092-8674(84)90322-2. [DOI] [PubMed] [Google Scholar]
  26. Searle P. F., Davison B. L., Stuart G. W., Wilkie T. M., Norstedt G., Palmiter R. D. Regulation, linkage, and sequence of mouse metallothionein I and II genes. Mol Cell Biol. 1984 Jul;4(7):1221–1230. doi: 10.1128/mcb.4.7.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shulman L., Revel M. Interferon-dependent induction of mRNA activity for (2'-5')oligo-isoadenylate synthetase. Nature. 1980 Nov 6;288(5786):98–100. doi: 10.1038/288098a0. [DOI] [PubMed] [Google Scholar]
  28. Tauber A. I., Babior B. M. Evidence for hydroxyl radical production by human neutrophils. J Clin Invest. 1977 Aug;60(2):374–379. doi: 10.1172/JCI108786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Taylor J. Inhibition of interferon action by actinomycin. Biochem Biophys Res Commun. 1964;14:447–451. doi: 10.1016/0006-291x(64)90084-1. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Varshney U., Jahroudi N., Foster R., Gedamu L. 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. 1986 Jan;6(1):26–37. doi: 10.1128/mcb.6.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weil J., Epstein C. J., Epstein L. B., Sedmak J. J., Sabran J. L., Grossberg S. E. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons. Nature. 1983 Feb 3;301(5899):437–439. doi: 10.1038/301437a0. [DOI] [PubMed] [Google Scholar]
  33. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]
  34. Yagle M. K., Palmiter R. D. Coordinate regulation of mouse metallothionein I and II genes by heavy metals and glucocorticoids. Mol Cell Biol. 1985 Feb;5(2):291–294. doi: 10.1128/mcb.5.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]

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