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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
. 1982 Oct;79(19):5778–5782. doi: 10.1073/pnas.79.19.5778

Differences in rates of tyrosine aminotransferase deinduction with cyclic AMP and glucocorticoids.

E J Lewis, P Calie, W D Wicks
PMCID: PMC346993  PMID: 6136964

Abstract

As an indirect test of the possibility that cyclic AMP produces its stimulatory effects on the synthesis of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) by stabilizing its mRNA, the kinetics of decline in the rate of synthesis of this enzyme was measured in rat hepatoma cells following inducer removal or addition of RNA synthesis inhibitors. In all cases in which cells were previously exposed to cyclic AMP, the decline in enzyme synthesis after removal of inducer or addition of inhibitors of RNA synthesis was 4 to 5 times more rapid than in cells exposed to a glucocorticoid (dexamethasone) which also induces the aminotransferase. Thus, it seems unlikely that cyclic AMP had been acting by stabilizing the mRNA that directs the synthesis of the aminotransferase. Possible explanations for these paradoxical results are suggested. A more rapid decline in enzyme synthesis was also seen in cells induced with both cyclic AMP and glucocorticoid, suggesting direct interaction between the two inducers.

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Selected References

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

  1. Barnett C. A., Wicks W. D. Regulation of phosphoenolpyruvate carboxykinase and tyrosine transaminase in hepatoma cell cultures. I. Effects of glucocorticoids, N 6 ,O 2' -dibutyryl cyclic adenosine 3',5'-monophosphate and insulin in Reuber H35 cells. J Biol Chem. 1971 Dec 10;246(23):7201–7206. [PubMed] [Google Scholar]
  2. Ernest M. J., Feigelson P. Increase in hepatic tyrosine aminotransferase mRNA during enzyme induction by N6,O2'-dibutyryl cyclic AMP. J Biol Chem. 1978 Jan 25;253(2):319–322. [PubMed] [Google Scholar]
  3. Fallon A. M., Jinks C. S., Strycharz G. D., Nomura M. Regulation of ribosomal protein synthesis in Escherichia coli by selective mRNA inactivation. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3411–3415. doi: 10.1073/pnas.76.7.3411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Farmer S. R., Ben-Ze'av A., Benecke B. J., Penman S. Altered translatability of messenger RNA from suspended anchorage-dependent fibroblasts: reversal upon cell attachment to a surface. Cell. 1978 Oct;15(2):627–637. doi: 10.1016/0092-8674(78)90031-4. [DOI] [PubMed] [Google Scholar]
  5. Hill R. E., Lee K. L., Kenney F. T. Effects of insulin on messenger RNA activities in rat liver. J Biol Chem. 1981 Feb 25;256(4):1510–1513. [PubMed] [Google Scholar]
  6. Kenney F. T., Lee K. L., Stiles C. D. Degradation of messenger RNA in mammalian cells. Acta Endocrinol Suppl (Copenh) 1972;168:369–380. doi: 10.1530/acta.0.071s369. [DOI] [PubMed] [Google Scholar]
  7. Miles M. F., Hung P., Jungmann R. A. Cyclic AMP regulation of lactate dehydrogenase. Quantitation of lactate dehydrogenase M-subunit messenger RNA in isoproterenol-and N6,O2'-dibutyryl cyclic AMP-stimulated rat C6 glioma cells by hybridization analysis using a cloned cDNA probe. J Biol Chem. 1981 Dec 10;256(23):12545–12552. [PubMed] [Google Scholar]
  8. Nickol J. M., Lee K. L., Kenney F. T. Changes in hepatic levels of tyrosine aminotransferase messenger RNA during induction by hydrocortisone. J Biol Chem. 1978 Jun 10;253(11):4009–4015. [PubMed] [Google Scholar]
  9. Noguchi T., Diesterhaft M., Granner D. Dibutyryl cyclic AMP increases the amount of functional messenger RNA coding for tyrosine aminotransferase in rat liver. J Biol Chem. 1978 Mar 10;253(5):1332–1335. [PubMed] [Google Scholar]
  10. Queen C., Rosenberg M. Differential translation efficiency explains discoordinate expression of the galactose operon. Cell. 1981 Jul;25(1):241–249. doi: 10.1016/0092-8674(81)90249-x. [DOI] [PubMed] [Google Scholar]
  11. Roper M. D., Wicks W. D. Evidence for acceleration of the rate of elongation of tyrosine aminotransferase nascent chains by dibutyryl cyclic AMP. Proc Natl Acad Sci U S A. 1978 Jan;75(1):140–144. doi: 10.1073/pnas.75.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schimke R. T., Doyle D. Control of enzyme levels in animal tissues. Annu Rev Biochem. 1970;39:929–976. doi: 10.1146/annurev.bi.39.070170.004433. [DOI] [PubMed] [Google Scholar]
  13. Segal S., Khoury G. Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5611–5615. doi: 10.1073/pnas.76.11.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sehgal P. B., Gupta S. L. Regulation of the stability of poly(I)xpoly(C)-induced human fibroblast interferon mRNA: selective inactivation of interferon mRNA and lack of involvement of 2',5'-oligo(A) synthetase activation during the shutoff of interferon production. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3489–3493. doi: 10.1073/pnas.77.6.3489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Snoek G. T., Voorma H. O., Van Wijk R. Further evidence for translational regulation of tyrosine aminotransferase synthesis by dibutyryl cyclic AMP in Reuber H35 hepatoma cells. Biochim Biophys Acta. 1981 Aug 27;655(1):107–112. doi: 10.1016/0005-2787(81)90073-3. [DOI] [PubMed] [Google Scholar]
  16. Stallcup M. R., Ring J., Yamamoto K. R. Synthesis of mouse mammary tumor virus ribonucleic acid in isolated nuclei from cultured mammary tumor cells. Biochemistry. 1978 Apr 18;17(8):1515–1521. doi: 10.1021/bi00601a025. [DOI] [PubMed] [Google Scholar]
  17. Steinberg R. A., Levinson B. B., Tomkins G. M. Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2007–2011. doi: 10.1073/pnas.72.6.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Swaneck G. E., Nordstrom J. L., Kreuzaler F., Tsai M. J., O'Malley B. W. Effect of estrogen on gene expression in chicken oviduct: evidence for transcriptional control of ovalbumin gene. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1049–1053. doi: 10.1073/pnas.76.3.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wicks W. D., McKibbin J. B. Evidence for translational regulation of specific enzyme synthesis by N 6 , O 2' -dibutyryl cyclic AMP in hepatoma cell cultures. Biochem Biophys Res Commun. 1972 Jul 11;48(1):205–211. doi: 10.1016/0006-291x(72)90364-6. [DOI] [PubMed] [Google Scholar]
  20. Wicks W. D. Regulation of protein synthesis by cyclic AMP. Adv Cyclic Nucleotide Res. 1974;4(0):335–438. [PubMed] [Google Scholar]
  21. Wicks W. D., Su J. L. Relationship between phosphorylation of tyrosine aminotransferase and regulation of its synthesis by cyclic AMP and hormones. J Cyclic Nucleotide Res. 1978 Apr;4(2):113–122. [PubMed] [Google Scholar]
  22. Wimalasena J., Leichtling B. H., Lewis E. J., Langan T. A., Wicks W. D. Coordinate regulation of adenylate cyclase, protein kinase, and specific enzyme synthesis by cholera toxin in hormonally unresponsive hepatoma cells. Arch Biochem Biophys. 1980 Dec;205(2):595–605. doi: 10.1016/0003-9861(80)90143-5. [DOI] [PubMed] [Google Scholar]
  23. Wimalasena J., Wicks W. D. Coordinate protein kinase activation and specific enzyme induction by cyclic nucleotide derivatives in intact cultured hepatoma cells. Mol Pharmacol. 1979 Sep;16(2):449–461. [PubMed] [Google Scholar]
  24. Young R. A., Hagenbüchle O., Schibler U. A single mouse alpha-amylase gene specifies two different tissue-specific mRNAs. Cell. 1981 Feb;23(2):451–458. doi: 10.1016/0092-8674(81)90140-9. [DOI] [PubMed] [Google Scholar]

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