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Feedback regulation of polyamine synthesis in Ehrlich ascites tumor cells. Analysis using nonmetabolizable derivatives of putrescine and spermine.

Abstract
Ornithine decarboxylase (ODC) is subject to feedback regulation by the polyamines. Thus, addition of putrescine, spermidine or spermine to cells causes inhibition of ODC mRNA translation. Putrescine and spermine are readily converted into spermidine. Therefore, it is conceivable that the inhibition of ODC synthesis observed in putrescine- and spermine-supplemented cells is instead an effect of spermidine. To examine this possibility we have used two analogs of putrescine and spermine, namely 1,4-dimethylputrescine and 5,8-dimethylspermine, which cannot be converted into spermidine. Both analogs were found to inhibit the incorporation of [35S]methionine into ODC protein to approximately the same extent, suggesting that putrescine as well as spermine exert a negative feedback control of ODC mRNA translation in the cell. In addition to suppressing ODC synthesis, both analogs were found to increase the turnover rate of the enzyme. 5,8-Dimethylspermine caused a marked decrease in the activity of S-adenosylmethionine decarboxylase (AdoMetDC). This effect was not obtained with 1,4-dimethylputrescine, indicating that spermine, but not putrescine, exerts a negative control of AdoMetDC. Treatment with 1,4-dimethylputrescine caused extensive depletion of the cellular putrescine and spermidine content, but accumulation of spermine. 5,8-Dimethylspermine treatment, on the other hand, effectively depleted the spermine content and had less effect on the putrescine and spermidine content, at least initially. Nevertheless, the total polyamine content was more extensively reduced by treatment with 5,8-dimethylspermine than with 1,4-dimethylputrescine. Accordingly, only 5,8-dimethylspermine treatment exerted a significant inhibitory effect on Ehrlich ascites tumor cell growth.
AuthorsI Holm, L Persson, O Heby, N Seiler
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 972 Issue 3 Pg. 239-48 (Dec 09 1988) ISSN: 0006-3002 [Print] Netherlands
PMID3196761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 5,8-dimethylspermine
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • RNA, Messenger
  • Spermine
  • 1,4-dimethylputrescine
  • Acetyltransferases
  • diamine N-acetyltransferase
  • Ornithine Decarboxylase
  • Adenosylmethionine Decarboxylase
  • Spermidine
  • Putrescine
Topics
  • Acetyltransferases (metabolism)
  • Adenosylmethionine Decarboxylase (metabolism)
  • Animals
  • Carcinoma, Ehrlich Tumor (metabolism, pathology)
  • Cell Division (drug effects)
  • Feedback
  • Ornithine Decarboxylase (genetics, metabolism)
  • Ornithine Decarboxylase Inhibitors
  • Polyamines (metabolism)
  • Protein Biosynthesis (drug effects)
  • Putrescine (analogs & derivatives, metabolism, pharmacology)
  • RNA, Messenger (metabolism)
  • Spermidine (metabolism, pharmacology)
  • Spermine (analogs & derivatives, metabolism, pharmacology)

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