Abstract
Regulation of the endogenous mouse metallothionein I and II (MT-I and MT-II) genes by heavy metals and glucocorticoids was studied in cultured mouse cells. Both mRNAs were measured simultaneously by solution hybridization with [3H]MT-I cDNA and [32P]MT-II cDNA, and the absolute amount of each mRNA was calculated by using a single-stranded M13 standard that contained both mRNA sequences. Both genes responded identically to different concentrations of metals (zinc, cadmium, and copper) and dexamethasone. Furthermore, the time courses of induction of both mRNAs were the same. However, under all conditions there was 1.2- to 1.9-fold more MT-I mRNA than MT-II mRNA. We conclude that both genes are regulated identically by receptors for glucocorticoids and metals but that the rate of transcription from the MT-I gene is slightly higher than from the MT-II gene.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brinster R. L., Chen H. Y., Warren R., Sarthy A., Palmiter R. D. Regulation of metallothionein--thymidine kinase fusion plasmids injected into mouse eggs. Nature. 1982 Mar 4;296(5852):39–42. doi: 10.1038/296039a0. [DOI] [PubMed] [Google Scholar]
- Cox D. R., Palmiter R. D. The metallothionein-I gene maps to mouse chromosome 8: implications for human Menkes' disease. Hum Genet. 1983;64(1):61–64. doi: 10.1007/BF00289481. [DOI] [PubMed] [Google Scholar]
- 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]
- Durnam D. M., Palmiter R. D. A practical approach for quantitating specific mRNAs by solution hybridization. Anal Biochem. 1983 Jun;131(2):385–393. doi: 10.1016/0003-2697(83)90188-4. [DOI] [PubMed] [Google Scholar]
- Durnam D. M., Palmiter R. D. Induction of metallothionein-I mRNA in cultured cells by heavy metals and iodoacetate: evidence for gratuitous inducers. Mol Cell Biol. 1984 Mar;4(3):484–491. doi: 10.1128/mcb.4.3.484. [DOI] [PMC free article] [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]
- Eaton D. L., Stacey N. H., Wong K. L., Klaassen C. D. Dose-response effects of various metal ions on rat liver metallothionein, glutathione, heme oxygenase, and cytochrome P-450. Toxicol Appl Pharmacol. 1980 Sep 15;55(2):393–402. doi: 10.1016/0041-008x(80)90101-5. [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]
- Kafatos F. C. The cocoonase zymogen cells of silk moths: a model of terminal cell differentiation for specific protein synthesis. Curr Top Dev Biol. 1972;7:125–191. doi: 10.1016/s0070-2153(08)60071-x. [DOI] [PubMed] [Google Scholar]
- Karin M., Andersen R. D., Slater E., Smith K., Herschman H. R. Metallothionein mRNA induction in HeLa cells in response to zinc or dexamethasone is a primary induction response. Nature. 1980 Jul 17;286(5770):295–297. doi: 10.1038/286295a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Karin M., Richards R. I. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene. Nature. 1982 Oct 28;299(5886):797–802. doi: 10.1038/299797a0. [DOI] [PubMed] [Google Scholar]
- Mayo K. E., Palmiter R. D. Glucocorticoid regulation of metallothionein-I mRNA synthesis in cultured mouse cells. J Biol Chem. 1981 Mar 25;256(6):2621–2624. [PubMed] [Google Scholar]
- Mayo K. E., Warren R., Palmiter R. D. The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. Cell. 1982 May;29(1):99–108. doi: 10.1016/0092-8674(82)90094-0. [DOI] [PubMed] [Google Scholar]
- Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
- Palmiter R. D., Norstedt G., Gelinas R. E., Hammer R. E., Brinster R. L. Metallothionein-human GH fusion genes stimulate growth of mice. Science. 1983 Nov 18;222(4625):809–814. doi: 10.1126/science.6356363. [DOI] [PubMed] [Google Scholar]
- Pavlakis G. N., Hamer D. H. Regulation of a metallothionein-growth hormone hybrid gene in bovine papilloma virus. Proc Natl Acad Sci U S A. 1983 Jan;80(2):397–401. doi: 10.1073/pnas.80.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Piotrowski J. K., Szymańska J. A. Influence of certain metals on the level of metallothionein-like proteins in the liver and kidneys of rats. J Toxicol Environ Health. 1976 Jul;1(6):991–1002. doi: 10.1080/15287397609529402. [DOI] [PubMed] [Google Scholar]
- 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]
- Schimke R. T. Methods for analysis of enzyme synthesis and degradation in animal tissues. Methods Enzymol. 1975;40:241–266. doi: 10.1016/s0076-6879(75)40020-9. [DOI] [PubMed] [Google Scholar]
- Schmidt C. J., Hamer D. H., McBride O. W. Chromosomal location of human metallothionein genes: implications for Menkes' disease. Science. 1984 Jun 8;224(4653):1104–1106. doi: 10.1126/science.6719135. [DOI] [PubMed] [Google Scholar]
- 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]
- Webb M., Cain K. Functions of metallothionein. Biochem Pharmacol. 1982 Jan 15;31(2):137–142. doi: 10.1016/0006-2952(82)90202-7. [DOI] [PubMed] [Google Scholar]