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. 1990 May 15;268(1):207–212. doi: 10.1042/bj2680207

Combined regulation of ornithine and S-adenosylmethionine decarboxylases by spermine and the spermine analogue N1 N12-bis(ethyl)spermine.

C W Porter 1, A E Pegg 1, B Ganis 1, R Madhabala 1, R J Bergeron 1
PMCID: PMC1131413  PMID: 2344358

Abstract

In the present study, the spermine (SPM) analogue N1N12-bis(ethyl)spermine (BESPM) is compared with SPM in its ability to regulate ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AdoMetDC) activities in intact L1210 cells and in the mechanism(s) by which this is accomplished. Unlike the comparable spermidine (SPD) analogue N1N8-bis(ethyl)spermidine, which regulates only ODC, BESPM suppresses both ODC and AdoMetDC activities. With 1 microM-SPM or -BESPM, near-maximal suppression of enzyme activity (i.e. less than 70%) was achieved after 2 h for ODC and 12 h for AdoMetDC. After such treatment, ODC activity fully recovered within 2-4 h, and that of AdoMetDC within 12 h, when cells were reseeded into drug-free media. It was deduced that an intracellular accumulation of BESPM or SPM equivalent to only approximately 200-450 pmol/10(6) cells was sufficient to fully invoke ODC regulatory mechanisms. Decreases in both enzyme activities after BESPM or SPM treatment were closely paralleled by concomitant decreases in the amount of enzyme protein. Since cellular ODC or AdoMetDC mRNA was not similarly decreased by either BESPM or SPM treatment, it was concluded that translational and/or post-translational mechanisms were probably responsible for enzyme regulation. In support of the former of these possibilities, it was demonstrated that both BESPM and SPM preferentially inhibited the translation in vitro of ODC and AdoMetDC relative to albumin in a reticulocyte-lysate system. On the basis of the consistent similarities between BESPM and SPM in all parameters studied, it is concluded that the analogue most likely acts by mechanisms identical with those by which SPM acts in suppressing polyamine biosynthesis.

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Selected References

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  1. Benson J. R., Hare P. E. O-phthalaldehyde: fluorogenic detection of primary amines in the picomole range. Comparison with fluorescamine and ninhydrin. Proc Natl Acad Sci U S A. 1975 Feb;72(2):619–622. doi: 10.1073/pnas.72.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berger F. G., Szymanski P., Read E., Watson G. Androgen-regulated ornithine decarboxylase mRNAs of mouse kidney. J Biol Chem. 1984 Jun 25;259(12):7941–7946. [PubMed] [Google Scholar]
  3. Bergeron R. J., Hawthorne T. R., Vinson J. R., Beck D. E., Jr, Ingeno M. J. Role of the methylene backbone in the antiproliferative activity of polyamine analogues on L1210 cells. Cancer Res. 1989 Jun 1;49(11):2959–2964. [PubMed] [Google Scholar]
  4. Bergeron R. J., Neims A. H., McManis J. S., Hawthorne T. R., Vinson J. R., Bortell R., Ingeno M. J. Synthetic polyamine analogues as antineoplastics. J Med Chem. 1988 Jun;31(6):1183–1190. doi: 10.1021/jm00401a019. [DOI] [PubMed] [Google Scholar]
  5. Casero R. A., Jr, Ervin S. J., Celano P., Baylin S. B., Bergeron R. J. Differential response to treatment with the bis(ethyl)polyamine analogues between human small cell lung carcinoma and undifferentiated large cell lung carcinoma in culture. Cancer Res. 1989 Feb 1;49(3):639–643. [PubMed] [Google Scholar]
  6. Gupta M., Coffino P. Mouse ornithine decarboxylase. Complete amino acid sequence deduced from cDNA. J Biol Chem. 1985 Mar 10;260(5):2941–2944. [PubMed] [Google Scholar]
  7. Holm I., Persson L., Stjernborg L., Thorsson L., Heby O. Feedback control of ornithine decarboxylase expression by polyamines. Analysis of ornithine decarboxylase mRNA distribution in polysome profiles and of translation of this mRNA in vitro. Biochem J. 1989 Mar 1;258(2):343–350. doi: 10.1042/bj2580343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kabra P. M., Lee H. K., Lubich W. P., Marton L. J. Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography: improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr. 1986 Jul 11;380(1):19–32. doi: 10.1016/s0378-4347(00)83621-x. [DOI] [PubMed] [Google Scholar]
  9. Kameji T., Pegg A. E. Effect of putrescine on the synthesis of S-adenosylmethionine decarboxylase. Biochem J. 1987 Apr 1;243(1):285–288. doi: 10.1042/bj2430285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kameji T., Pegg A. E. Inhibition of translation of mRNAs for ornithine decarboxylase and S-adenosylmethionine decarboxylase by polyamines. J Biol Chem. 1987 Feb 25;262(6):2427–2430. [PubMed] [Google Scholar]
  11. Katz A., Kahana C. Isolation and characterization of the mouse ornithine decarboxylase gene. J Biol Chem. 1988 Jun 5;263(16):7604–7609. [PubMed] [Google Scholar]
  12. Katz A., Kahana C. Transcriptional activation of mammalian ornithine decarboxylase during stimulated growth. Mol Cell Biol. 1987 Jul;7(7):2641–2643. doi: 10.1128/mcb.7.7.2641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pajunen A., Crozat A., Jänne O. A., Ihalainen R., Laitinen P. H., Stanley B., Madhubala R., Pegg A. E. Structure and regulation of mammalian S-adenosylmethionine decarboxylase. J Biol Chem. 1988 Nov 15;263(32):17040–17049. [PubMed] [Google Scholar]
  14. Pegg A. E., Madhubala R., Kameji T., Bergeron R. J. Control of ornithine decarboxylase activity in alpha-difluoromethylornithine-resistant L1210 cells by polyamines and synthetic analogues. J Biol Chem. 1988 Aug 5;263(22):11008–11014. [PubMed] [Google Scholar]
  15. Pegg A. E. Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res. 1988 Feb 15;48(4):759–774. [PubMed] [Google Scholar]
  16. Pegg A. E., Pösö H. S-adenosylmethionine decarboxylase (rat liver). Methods Enzymol. 1983;94:234–239. doi: 10.1016/s0076-6879(83)94041-7. [DOI] [PubMed] [Google Scholar]
  17. Pegg A. E. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J. 1986 Mar 1;234(2):249–262. doi: 10.1042/bj2340249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pera P. J., Kramer D. L., Sufrin J. R., Porter C. W. Comparison of the biological effects of four irreversible inhibitors of ornithine decarboxylase in two murine lymphocytic leukemia cell lines. Cancer Res. 1986 Mar;46(3):1148–1154. [PubMed] [Google Scholar]
  19. Persson L., Holm I., Stjernborg L., Heby O. Regulation of polyamine synthesis in mammalian cells. Adv Exp Med Biol. 1988;250:261–271. doi: 10.1007/978-1-4684-5637-0_24. [DOI] [PubMed] [Google Scholar]
  20. Persson L., Stjernborg L., Holm I., Heby O. Polyamine-mediated control of mammalian S-adenosyl-L-methionine decarboxylase expression: effects on the content and translational efficiency of the mRNA. Biochem Biophys Res Commun. 1989 May 15;160(3):1196–1202. doi: 10.1016/s0006-291x(89)80130-5. [DOI] [PubMed] [Google Scholar]
  21. Porter C. W., Berger F. G., Pegg A. E., Ganis B., Bergeron R. J. Regulation of ornithine decarboxylase activity by spermidine and the spermidine analogue N1N8-bis(ethyl)spermidine. Biochem J. 1987 Mar 1;242(2):433–440. doi: 10.1042/bj2420433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Porter C. W., Bergeron R. J. Enzyme regulation as an approach to interference with polyamine biosynthesis--an alternative to enzyme inhibition. Adv Enzyme Regul. 1988;27:57–79. doi: 10.1016/0065-2571(88)90009-x. [DOI] [PubMed] [Google Scholar]
  23. Porter C. W., Cavanaugh P. F., Jr, Stolowich N., Ganis B., Kelly E., Bergeron R. J. Biological properties of N4- and N1,N8-spermidine derivatives in cultured L1210 leukemia cells. Cancer Res. 1985 May;45(5):2050–2057. [PubMed] [Google Scholar]
  24. Porter C. W., McManis J., Casero R. A., Bergeron R. J. Relative abilities of bis(ethyl) derivatives of putrescine, spermidine, and spermine to regulate polyamine biosynthesis and inhibit L1210 leukemia cell growth. Cancer Res. 1987 Jun 1;47(11):2821–2825. [PubMed] [Google Scholar]
  25. Porter C. W., McManis J., Lee D., Bergeron R. J. Selective regulation of S-adenosylmethionine decarboxylase activity by the spermine analogue 6-spermyne. Biochem J. 1988 Sep 1;254(2):337–342. doi: 10.1042/bj2540337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Porter C. W., Sufrin J. R. Interference with polyamine biosynthesis and/or function by analogs of polyamines or methionine as a potential anticancer chemotherapeutic strategy. Anticancer Res. 1986 Jul-Aug;6(4):525–542. [PubMed] [Google Scholar]
  27. Seely J. E., Pegg A. E. Ornithine decarboxylase (mouse kidney). Methods Enzymol. 1983;94:158–161. doi: 10.1016/s0076-6879(83)94025-9. [DOI] [PubMed] [Google Scholar]
  28. Sertich G. J., Pegg A. E. Polyamine administration reduces ornithine decarboxylase activity without affecting its mRNA content. Biochem Biophys Res Commun. 1987 Mar 13;143(2):424–430. doi: 10.1016/0006-291x(87)91371-4. [DOI] [PubMed] [Google Scholar]
  29. Shirahata A., Christman K. L., Pegg A. E. Quantitation of S-adenosylmethionine decarboxylase protein. Biochemistry. 1985 Jul 30;24(16):4417–4423. doi: 10.1021/bi00337a024. [DOI] [PubMed] [Google Scholar]

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