Translational regulation of ornithine decarboxylase by polyamines

Persson, Lo; Holm, Ingvar; Heby, Olle

doi:10.1016/0014-5793(86)80892-4

Cited by 97 publications

(57 citation statements)

References 19 publications

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“…It has also been reported that, directly adding large concentrations of putrescine to tissue culture systems, does not affect the levels of the induced ornithine decarboxylase mRNA (Holtta and Pohjanpelto, 1986;Persson, Holm and Heby, 1986). Polyamines may exert a negative feedback inhibition of the rate of translation of the ornithine decarboxylase mRNA.…”

Section: Inducedmentioning

confidence: 99%

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

1991

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Summary-The induction of the activity of cerebral ornithine decarboxylase (EC 4.1.1.17) and mRNA by electrical stimulation exhibits regional differences. The effects of the enzyme inhibitor difluoromethylornithine on these regional variations was examined. Administration of this inhibitor resulted in pronounced depression of both basal and induced activity of ornithine decarboxylase in the hippocampus. Basal activity of the enzyme in the neocortex and the cerebellum appeared to be resistant to difluoromethylornithine but the induced enzyme activity was sensitive to the effects ofthis inhibitor. Susceptibility to difluoromethylornithine may be directly correlated with a slower turnover rate for ornithine decarboxylase. These results suggest that ornithine decarboxylase in the hippocampus may possess a longer half-life than its counterparts in other regions of the brain. Pretreatment with difluoromethylornithine had no effect on the induced ornithine decarboxylase mRNA in the neocortex. Thus, elevated activity of ornithine decarboxylase enzyme, due to electrical stimulation, appears to not have any effect on either the transcription or the decay rate of the induced ornithine decarboxylase mRNA. These findings support the concept of region-specific regulation of cerebral ornithine decarboxylase.

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Section: Inducedmentioning

confidence: 99%

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

1991

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“…The extract was then centrifuged for 20 rain at 20,000 x g at 4°C. SSAT, S-adenosylmethionine decarboxylase and ornithine decarboxylase activities were determined in aliqaots of the supernatant essentially as described earlier [20,21].…”

Section: Determination Of Enzyme Activitiesmentioning

confidence: 99%

Effects of transient expression of spermidine/spermine N¹‐acetyltransferase in COS cells

Vargiu

Persson

1994

FEBS Letters

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Mammalian spermidine/spermine NLacetyltransferase (SSAT) was transiently expressed in COS cells. As compared to COS cells transfected with control vector alone, cells transfected with the expression vector containing SSAT cDNA contained lower concentrations of spermidine and spermine. The putrescine content, on the other hand, was markedly increased in the COS cells expressing large amounts of SSAT. These changes in polyamine content were most likely caused by an interconversion of spermine and spermidine into putrescine. The SSAT-induced changes in cellular polyamine content resulted in a compensatory increase in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, i.e. the enzymes catalyzing the rate-limiting steps in polyamine biosynthesis. This is the first demonstration that a primary increase in SSAT activity will induce an interconversion-like change in the polyamine levels and the physiological role of SSAT is most likely to protect cells against too high concentrations of spermidine and spermine.

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“…To ascertain that the feedback control of ODC was effective in the non-transfected COS cells, ODC activity was measured in cells grown in the presence or absence of 10 pM spermidine. This concentration of spermidine is high enough to inhibit the synthesis of ODC in other mammalian cells [16,17, 191. A marked increase in ODC activity was observed in COS cells during their exponential growth (Fig.…”

mentioning

confidence: 99%

“…However, to obtain this effect large quantities of polyamines, often at millimolar concentrations, have to be used. Nevertheless, ODC is downregulated by the addition of micromolar concentrations of polyamines to cells [14,16,17, 191. Furthermore, treatment with polyamine synthesis inhibitors causes a marked increase in cellular ODC content which cannot be explained by a change in the apparent turnover of the enzyme [13,14, 191.…”

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confidence: 99%

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Feedback regulation of mammalian ornithine decarboxylase

Lövkvist

Stjernborg

Persson

1993

European Journal of Biochemistry

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Ornithine decarboxylase catalyzes the first step in the biosynthesis of polyamines in mammalian cells. The enzyme is subject to various control mechanisms to maintain adequate intracellular levels of polyamines. Polyamines exert a strong feedback control on ornithine decarboxylase. In a recent study [van Daalen Wetters, T., Macrae, M., Brabant, M., Sittler, A. & Coffino, P. (1989) Mol. Cell. Biol. 9, 5484-54901, it was concluded that feedback control of ornithine decarboxylase is mainly, if not exclusively, a posttranslational phenomenon. The existence of a fast-acting polyamine-stimulated component of ornithine decarboxylase degradation that acts on newly synthesized monomeric forms of the enzyme was postulated. In the present study we have used a transient expression system to test this hypothesis. The expression of ornithine decarboxylase in mock-transfected COS cells varied depending on the cellular supply of polyamines as has been found in other mammalian cells. Thus, supplementing the cells with exogenous spermidine resulted in a marked decrease in ornithine decarboxylase activity, whereas depletion of intracellular polyamines, using an ornithine decarboxylase inhibitor, gave a large increase in the cellular content of the enzyme. COS cells expressing an ornithine decarboxylase mRNA devoid of its 5' non-translated region did not exhibit any feedback control of the enzyme, neither in the presence of exogenous spennidine nor when the intracellular polyamine levels were depleted to the same extent as in the mock-transfected COS cells. The results strongly suggest that the feedback control of ornithine decarboxylase is not merely a posttranslational phenomenon.Cell proliferation is dependent on an adequate supply of the polyamines putrescine, spermidine and spennine [ 1 -31. The first step in the biosynthesis of polyamines is catalyzed by ornithine decarboxylase (ODC), which is regulated by a multitude of mechanisms [4]. Induction of cell growth is often accompanied by an increased transcription of the ODC gene. In many cases the increase in ODC mRNA is much less than the increase observed in ODC activity [5-91. This may partly be explained by a stabilization of the enzyme. However, part of the increase in ODC activity appears to be due to an increase in the efficiency of ODC mRNA translation. Since the turnover of ODC is among the fastest known for a mammalian enzyme [lo], any change in the synthesis or degradation of ODC will rapidly be manifested in a change in the enzyme activity [ll].Polyamines exert a strong feedback control on ODC. A decrease in cellular polyamine content will rapidly cause an increase in the amount of ODC regulation. It has been demonstrated that the turnover of ODC is stimulated when cells are exposed to an excess of extracellular polyamines [17, 181. However, to obtain this effect large quantities of polyamines, often at millimolar concentrations, have to be used. Nevertheless, ODC is downregulated by the addition of micromolar concentrations of polyamines to cells [14,16,17, 191....

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Translational regulation of ornithine decarboxylase by polyamines

Cited by 97 publications

References 19 publications

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

Effects of transient expression of spermidine/spermine N¹‐acetyltransferase in COS cells

Feedback regulation of mammalian ornithine decarboxylase

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Translational regulation of ornithine decarboxylase by polyamines

Cited by 97 publications

References 19 publications

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

Differential effects of difluoromethylornithine on basal and induced activity of cerebral ornithine decarboxylase and mRNA

Effects of transient expression of spermidine/spermine N1‐acetyltransferase in COS cells

Feedback regulation of mammalian ornithine decarboxylase

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Effects of transient expression of spermidine/spermine N¹‐acetyltransferase in COS cells