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. 1993 Apr 15;291(Pt 2):505–508. doi: 10.1042/bj2910505

Transgenic mice over-producing putrescine in their tissues do not convert the diamine into higher polyamines.

M Halmekytö 1, L Alhonen 1, L Alakuijala 1, J Jänne 1
PMCID: PMC1132553  PMID: 8484731

Abstract

We recently described a transgenic mouse line over-expressing the human ornithine decarboxylase gene virtually in all tissues. Despite strikingly elevated tissue putrescine concentrations, no or minimal changes were found in the levels of the higher polyamines spermidine and spermine. We have now extended these studies by further increasing tissue putrescine with the aid of 5-fluoromethylornithine, a specific inhibitor of ornithine transaminase and hence the catabolism of L-ornithine. As a result of the treatment with the latter drug, the concentration of putrescine was further increased by a factor of 2-3 without any changes in the concentrations of spermidine and spermine. In the testis of transgenic mice treated with 5-fluoromethylornithine, the concentration of putrescine was nearly 60 times that in non-transgenic untreated animals, yet the concentration of spermidine was only 1.5-fold higher. A similar small increase in brain spermidine was accompanied by a 40-fold elevation in the concentration of putrescine. The apparent blockade between putrescine and spermidine was in all likelihood not attributable to an inhibition of S-adenosylmethionine decarboxylase, the rate-controlling enzyme in the biosynthesis of spermidine and spermine. Our results are more compatible with the view that in non-dividing adult tissues putrescine is sequestered through some unknown mechanisms in a way that makes it unavailable for the synthesis of the higher polyamines.

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Selected References

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

  1. Daune G., Gerhart F., Seiler N. 5-Fluoromethylornithine, an irreversible and specific inhibitor of L-ornithine:2-oxo-acid aminotransferase. Biochem J. 1988 Jul 15;253(2):481–488. doi: 10.1042/bj2530481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Davis R. H., Morris D. R., Coffino P. Sequestered end products and enzyme regulation: the case of ornithine decarboxylase. Microbiol Rev. 1992 Jun;56(2):280–290. doi: 10.1128/mr.56.2.280-290.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Halmekytö M., Alhonen L., Wahlfors J., Sinervirta R., Eloranta T., Jänne J. Characterization of a transgenic mouse line over-expressing the human ornithine decarboxylase gene. Biochem J. 1991 Sep 15;278(Pt 3):895–898. doi: 10.1042/bj2780895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Halmekytö M., Alhonen L., Wahlfors J., Sinervirta R., Jänne O. A., Jänne J. Position-independent, aberrant expression of the human ornithine decarboxylase gene in transgenic mice. Biochem Biophys Res Commun. 1991 Oct 15;180(1):262–267. doi: 10.1016/s0006-291x(05)81286-0. [DOI] [PubMed] [Google Scholar]
  5. Halmekytö M., Hyttinen J. M., Sinervirta R., Utriainen M., Myöhänen S., Voipio H. M., Wahlfors J., Syrjänen S., Syrjänen K., Alhonen L. Transgenic mice aberrantly expressing human ornithine decarboxylase gene. J Biol Chem. 1991 Oct 15;266(29):19746–19751. [PubMed] [Google Scholar]
  6. Hannonen P., Raina A., Jänne J. Polyamine synthesis in the regenerating rat liver: stimulation of S-adenosyl methionine decarboxylase, and spermidine and spermine synthases after partial hepatectomy. Biochim Biophys Acta. 1972 Jun 26;273(1):84–90. doi: 10.1016/0304-4165(72)90194-8. [DOI] [PubMed] [Google Scholar]
  7. Hyvönen T., Keinänen T. A., Khomutov A. R., Khomutov R. M., Eloranta T. O. Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography. J Chromatogr. 1992 Feb 7;574(1):17–21. doi: 10.1016/0378-4347(92)80093-6. [DOI] [PubMed] [Google Scholar]
  8. Hölttä E., Jänne J. Ornithine decarboxylase activity and the accumulation of putrescine at early stages of liver regeneration. FEBS Lett. 1972 Jun 1;23(1):117–121. doi: 10.1016/0014-5793(72)80298-9. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Jänne J. Studies on the biosynthetic pathway of polyamines in rat liver. Acta Physiol Scand Suppl. 1967;300:1–71. [PubMed] [Google Scholar]
  11. Jänne J., Williams-Ashman H. G. On the purification of L-ornithine decarboxylase from rat prostate and effects of thiol compounds on the enzyme. J Biol Chem. 1971 Mar 25;246(6):1725–1732. [PubMed] [Google Scholar]
  12. Käpyaho K., Jänne J. Regulation of putrescine metabolism in Ehrlich ascites carcinoma cells exposed to hypotonic medium. Biochim Biophys Acta. 1982 Jan 12;714(1):93–100. [PubMed] [Google Scholar]
  13. 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]
  14. Pegg A. E., Williams-Ashman H. G. Stimulation of the decarboxylation of S-adenosylmethionine by putrescine in mammalian tissues. Biochem Biophys Res Commun. 1968 Jan 11;30(1):76–82. doi: 10.1016/0006-291x(68)90715-8. [DOI] [PubMed] [Google Scholar]
  15. Poulin R., Wechter R. S., Pegg A. E. An early enlargement of the putrescine pool is required for growth in L1210 mouse leukemia cells under hypoosmotic stress. J Biol Chem. 1991 Apr 5;266(10):6142–6151. [PubMed] [Google Scholar]
  16. Seiler N., Daune G., Bolkenius F. N., Knödgen B. Ornithine aminotransferase activity, tissue ornithine concentrations and polyamine metabolism. Int J Biochem. 1989;21(4):425–432. doi: 10.1016/0020-711x(89)90367-4. [DOI] [PubMed] [Google Scholar]

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