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. 1985 Feb 15;226(1):105–112. doi: 10.1042/bj2260105

An inhibitor of ornithine decarboxylase in the thymus and spleen of dexamethasone-treated rats.

P B Bishop, J Young, T Peng, J F Richards
PMCID: PMC1144682  PMID: 3977859

Abstract

A marked decrease in activity of ornithine decarboxylase in thymus and spleen occurs soon after treatment of rats with a glucocorticoid. In the present study, evidence was obtained that extracts of these tissues prepared 5 h after administration of dexamethasone, when the enzyme activity is very low, contain an inhibitor of ornithine decarboxylase. The inhibitor is also present at 12 h after treatment and, in lesser amount, at 2.5 h, but was not evident at 24 h. The inhibitory activity was destroyed by treatment with heat or with trypsin, and was not lost on dialysis of the extract. Preliminary experiments indicate that the Mr of the inhibitor is greater than 50 000, which differentiates it from antizyme, an inhibitor of ornithine decarboxylase found in several other cell types. The inhibitor seems to act by a non-catalytic and non-competitive mechanism. The inhibition is dependent on the amount of inhibitor and does not change with time. Since inhibition is not changed by dialysis of the inhibitory extract, its activity apparently does not require small-Mr substances. This differentiates it from inhibitors which inactivate ornithine decarboxylase by covalent modification, such as the polyamine-dependent protein kinase or transglutaminase. The formation of this inhibitor is an early event in lymphoid tissues in response to dexamethasone and may be important in causing the inhibition of cell division which precedes the destruction of lymphocytes.

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Selected References

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

  1. Atkins F. L., Beaven M. A. Ornithine decarboxylase and histaminase (diamine oxidase) activities in rat thymus and their relationship to the thymus lymphocyte. Biochem Pharmacol. 1975 Apr 1;24(7):763–768. doi: 10.1016/0006-2952(75)90117-3. [DOI] [PubMed] [Google Scholar]
  2. Bachrach U. Physiological aspects of ornithine decarboxylase. Cell Biochem Funct. 1984 Jan;2(1):6–10. doi: 10.1002/cbf.290020103. [DOI] [PubMed] [Google Scholar]
  3. Beaven M. A., de Jong W. Presence of histaminase and ornithine decarboxylase activities in rat thymus. Biochem Pharmacol. 1973 Jan 15;22(2):257–265. doi: 10.1016/0006-2952(73)90278-5. [DOI] [PubMed] [Google Scholar]
  4. Boucek R. J., Jr, Lembach K. J. Purification by affinity chromatography and preliminary characterization of ornithine decarboxylase from simian virus 40-transformed 3T3 mouse fibroblasts. Arch Biochem Biophys. 1977 Dec;184(2):408–415. doi: 10.1016/0003-9861(77)90368-x. [DOI] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Brosnan M. E., Farrell R., Wilansky H., Williamson D. H. Effect of starvation and refeeding on polyamine concentrations and ornithine decarboxylase antizyme in mammary gland of lactating rats. Biochem J. 1983 Apr 15;212(1):149–153. doi: 10.1042/bj2120149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Canellakis E. S., Viceps-Madore D., Kyriakidis D. A., Heller J. S. The regulation and function of ornithine decarboxylase and of the polyamines. Curr Top Cell Regul. 1979;15:155–202. [PubMed] [Google Scholar]
  8. Claman H. N. Corticosteroids and lymphoid cells. N Engl J Med. 1972 Aug 24;287(8):388–397. doi: 10.1056/NEJM197208242870806. [DOI] [PubMed] [Google Scholar]
  9. DOUGHERTY T. F. Effect of hormones on lympatic tissue. Physiol Rev. 1952 Oct;32(4):379–401. doi: 10.1152/physrev.1952.32.4.379. [DOI] [PubMed] [Google Scholar]
  10. Erwin B. G., Seely J. E., Pegg A. E. Mechanism of stimulation of ornithine decarboxylase activity in transformed mouse fibroblasts. Biochemistry. 1983 Jun 7;22(12):3027–3032. doi: 10.1021/bi00281a037. [DOI] [PubMed] [Google Scholar]
  11. Fong W. F., Heller J. S., Canellakis E. S. The appearance of an ornithine decarboxylase inhibitory protein upon the addition of putrescine to cell cultures. Biochim Biophys Acta. 1976 Apr 23;428(2):456–465. doi: 10.1016/0304-4165(76)90054-4. [DOI] [PubMed] [Google Scholar]
  12. Friedman Y., Park S., Levasseur S., Burke G. Regulation of thyroid ornithine decarboxylase by the polyamines. Induction of a protein inhibitor of ornithine decarboxylase by the end-products of the reaction. Biochim Biophys Acta. 1977 Dec 22;500(2):291–303. doi: 10.1016/0304-4165(77)90021-6. [DOI] [PubMed] [Google Scholar]
  13. Greengard O., Machovich R. Hydrocortisone regulation of thymidine kinase in thymus involution and hematopoietic tissues. Biochim Biophys Acta. 1972 Dec 29;286(2):382–388. doi: 10.1016/0304-4165(72)90274-7. [DOI] [PubMed] [Google Scholar]
  14. Insel P. A., Fenno J. Cyclic AMP-dependent protein kinase mediates a cyclic AMP-stimulated decrease in ornithine and S-adenosylmethionine decarboxylase activities. Proc Natl Acad Sci U S A. 1978 Feb;75(2):862–865. doi: 10.1073/pnas.75.2.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Insel P. A., Honeysett J. M. Glucocorticoid-mediated inhibition of ornithine decarboxylyase activity in S49 lymphoma cells. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5669–5672. doi: 10.1073/pnas.78.9.5669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jänne J., Pösö H., Raina A. Polyamines in rapid growth and cancer. Biochim Biophys Acta. 1978 Apr 6;473(3-4):241–293. doi: 10.1016/0304-419x(78)90015-x. [DOI] [PubMed] [Google Scholar]
  17. Kallio A., Löfman M., Pösö H., Jänne J. Diamine-induced inhibition of liver ornithine decarboxylase. Biochem J. 1979 Jan 1;177(1):63–69. doi: 10.1042/bj1770063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuehn G. D., Atmar V. J. Posttranslational control of ornithine decarboxylase by polyamine-dependent protein kinase. Fed Proc. 1982 Dec;41(14):3078–3083. [PubMed] [Google Scholar]
  19. Lesiewicz J., Goldsmith L. A. Antizyme release is an early event in ornithine decarboxylase induction by hair plucking. J Invest Dermatol. 1983 Feb;80(2):97–100. doi: 10.1111/1523-1747.ep12531681. [DOI] [PubMed] [Google Scholar]
  20. McCann P. P., Tardif C., Mamont P. S. Regulation of ornithine decarboxylase by ODC-antizyme in HTC cells. Biochem Biophys Res Commun. 1977 Apr 25;75(4):948–954. doi: 10.1016/0006-291x(77)91474-7. [DOI] [PubMed] [Google Scholar]
  21. Morris D. R., Fillingame R. H. Regulation of amino acid decarboxylation. Annu Rev Biochem. 1974;43(0):303–325. doi: 10.1146/annurev.bi.43.070174.001511. [DOI] [PubMed] [Google Scholar]
  22. Nawata H., Yamamoto R. S., Poirier L. A. Ornithine decarboxylase induction and polyamine levels in the kidney of estradiol-treated castrated male rats. Life Sci. 1980 Mar 3;26(9):689–698. doi: 10.1016/0024-3205(80)90258-1. [DOI] [PubMed] [Google Scholar]
  23. Nicholson M. L., Young D. A. Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798. Cancer Res. 1978 Nov;38(11 Pt 1):3673–3680. [PubMed] [Google Scholar]
  24. Prouty W. F. Ornithine decarboxylase inactivation in HeLa cells. J Cell Physiol. 1976 Sep;89(1):65–76. doi: 10.1002/jcp.1040890107. [DOI] [PubMed] [Google Scholar]
  25. Richards J. F., Beer C. T., Bourgeault C., Chen K., Gout P. W. Biochemical response of lymphoma cells to mitogenic stimulation by prolactin. Mol Cell Endocrinol. 1982 Apr;26(1-2):41–49. doi: 10.1016/0303-7207(82)90005-3. [DOI] [PubMed] [Google Scholar]
  26. Richards J. F., Lit K., Fuca R., Bourgeault C. Multiple species of ornithine decarboxylase in rat tissues: effects of dexamethasone. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1461–1467. doi: 10.1016/0006-291x(81)90783-x. [DOI] [PubMed] [Google Scholar]
  27. Richards J. F. Ornithine decarboxylase activity in lymphoid tissues of rats: effects of glucocorticoids. Life Sci. 1978 Oct 16;23(15):1619–1623. doi: 10.1016/0024-3205(78)90590-8. [DOI] [PubMed] [Google Scholar]
  28. Russell D. H., Haddox M. K., Gehring U. Effects of dexamethasone and dibutyryl cyclic AMP on polyamine synthesizing enzymes in mouse lymphoma cells. J Cell Physiol. 1981 Mar;106(3):375–384. doi: 10.1002/jcp.1041060307. [DOI] [PubMed] [Google Scholar]
  29. Russell D. H. Ornithine decarboxylase as a biological and pharmacological tool. Pharmacology. 1980;20(3):117–129. doi: 10.1159/000137355. [DOI] [PubMed] [Google Scholar]
  30. Russell D. H. Posttranslational modification of ornithine decarboxylase by its product putrescine. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1167–1172. doi: 10.1016/0006-291x(81)90741-5. [DOI] [PubMed] [Google Scholar]
  31. Scalabrino G., Ferioli M. E., Basagni M., Nebuloni R., Fraschini F. Endocrine regulation of thymic biosynthetic polyamine decarboxylases in adult rat. Am J Physiol. 1979 Jul;237(1):E6–10. doi: 10.1152/ajpendo.1979.237.1.E6. [DOI] [PubMed] [Google Scholar]
  32. Seely J. E., Pegg A. E. Changes in mouse kidney ornithine decarboxylase activity are brought about by changes in the amount of enzyme protein as measured by radioimmunoassay. J Biol Chem. 1983 Feb 25;258(4):2496–2500. [PubMed] [Google Scholar]
  33. Tabor C. W., Tabor H. 1,4-Diaminobutane (putrescine), spermidine, and spermine. Annu Rev Biochem. 1976;45:285–306. doi: 10.1146/annurev.bi.45.070176.001441. [DOI] [PubMed] [Google Scholar]
  34. Thomas N., Bell P. A. Glucocorticoid-induced cell-size changes and nuclear fragility in rat thymocytes. Mol Cell Endocrinol. 1981 Apr;22(1):71–84. doi: 10.1016/0303-7207(81)90103-9. [DOI] [PubMed] [Google Scholar]
  35. Thomas N., Edwards J. L., Bell P. A. Studies of the mechanism of glucocorticoid-induced pyknosis in isolated rat thymocytes. J Steroid Biochem. 1983 May;18(5):519–524. doi: 10.1016/0022-4731(83)90125-5. [DOI] [PubMed] [Google Scholar]

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