Polyamine depletion results in impairment of polyribosome formation and protein synthesis before onset of DNA synthesis in mitogen-activated human lymphocytes

Hölttä, Erkki; Hovi, Tapani

doi:10.1111/j.1432-1033.1985.tb09188.x

Cited by 33 publications

(8 citation statements)

References 39 publications

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“…It is well known that polyamines are required for optimal rates of protein synthesis (43), and this is part of the reason that polyamine starvation impairs growth. We have observed a serious impairment of general polysome formation (69) upon starvation for spermidine, which is in keeping with the findings of other workers (34). It is, therefore, possible that ODC mRNA is slightly more affected by starvation than other mRNAs because of its unusual precoding sequence.…”

Section: Discussionsupporting

confidence: 78%

Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA.

Williams¹,

Barnett²,

Ristow³

et al. 1992

Mol. Cell. Biol.

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Ornithine decarboxylase (ODC), which initiates the biosynthesis of the polyamines putrescine, spermidine, and spermine, is encoded by the spe-l gene of the fungus Neurospora crassa. This gene and its cDNA have been cloned and sequenced. The gene has a single 70-nucleotide intron in the coding sequence. The cDNA, comprising the entire coding region, recognizes a single 2.4-kb mRNA in Northern (RNA) blots. The mRNA transcript, defined by SI mapping, has an extremely long, 535-base leader without strong secondary-structure features or an upstream reading frame. The translational start of the protein is ambiguous: a Met-Val-Met sequence precedes the Pro known to be the N terminus of the ODC polypeptide. The polypeptide encoded by the N. crassa spe-l gene (484 amino acids) has 46% amino acid identity with that of Saccharomyces cerevisiae (466 amino acids) and 42% with that of mouse (461 amino acids). Alignment of the longer N. crassa sequence with S. cerevisiae and mouse sequences creates gaps in different sites in the S. cerevisiae and mouse sequences, suggesting that N. crassa ODC is closer to an ancestral form of the enzyme than that of either yeast or mouse ODC. N. crassa ODC, which turns over rapidly in vivo in the presence of polyamines, has two PEST sequences, found in most ODCs and other proteins with rapid turnover. In striking contrast to other eucaryotic organisms, the variation in the rate of ODC synthesis in response to polyamines in N. crassa is largely correlated with proportional changes in the abundance of ODC mRNA. Spermidine is the main effector of repression, while putrescine has a weaker effect. However, putrescine accumulation appears to increase the amount of active ODC that is made from a given amount of ODC mRNA, possibly by improving its translatability. Conversely, prolonged starvation for both putrescine and spermidine leads to the differentially impaired translation of ODC mRNA.Ornithine decarboxylase (ODC) catalyzes the decarboxylation of ornithine to form putrescine, the first step in polyamine biosynthesis leading to spermidine and spermine formation (Fig. 1). In most organisms, ODC is a dimer of 52,000-to 55,000-Da subunits, the activity of which is highly regulated in response to growth stimuli and to the polyamines themselves (31,50,62,63). The amplitude, the speed, and the unusual mechanisms of regulation of the enzyme suggest to many researchers that ODC and the polyamines have a special relationship to growth. Accordingly, many molecular studies of this enzyme in organisms ranging from bacteria to humans have appeared in the last few years (3,5,22,28,37).The most conspicuous features of ODC regulation in mammals in response to polyamines are the control of ODC synthesis without a change in ODC mRNA levels and the polyamine-induced increase in the turnover rate of the enzyme (31). In the fungus Neurospora crassa, the regulatory responses of ODC at the level of enzyme protein are the same as in many mammalian systems (3,16). In this study, we describe the sequence of the cloned OD...

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Section: Discussionsupporting

confidence: 78%

Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA.

Williams¹,

Barnett²,

Ristow³

et al. 1992

Mol. Cell. Biol.

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“…Upon stimulation with mitogen, lymphocytes resume DNA synthesis and proliferation, as well as polyamine synthesis. Polyamines are essential for cell proliferation, because inhibitors of polyamine synthesis reduce the rate of DNA replication and synthesis (43,44). In addition to their de novo polyamine synthesis, cells, including PBMCs, can take up polyamines from their surroundings (21,22).…”

Section: Discussionmentioning

confidence: 99%

Spermine, a Natural Polyamine, Suppresses LFA-1 Expression on Human Lymphocyte

Soda¹,

Kano²,

Nakamura³

et al. 2005

The Journal of Immunology

113

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Natural polyamines, spermine, spermidine, and putrescine, play a pivotal role in the regulation of gene expression; therefore, the age-dependent decreases and the disease-dependent increases in polyamine synthesis suggest a possible contribution of polyamines to the age-related and disease-associated changes in cellular function. In this study, we examined the effects of polyamines on the cellular function and the expression of adhesion molecules on human PBMCs from healthy volunteers. Flow cytometry revealed that PBMCs cultured with spermine decreased mean fluorescent intensities (MFIs) of CD11a and CD18 in the lymphocyte light-scattered region, but not in the monocyte region. This suppression was observed in a dose- and time-dependent manner and found nonspecifically on all cell subsets we tested (CD3+, CD4+, CD8+, CD19+, CD45RA+, CD45RO+, CD4+CD45RA+, CD4+CD45RO+, CD8+CD45RA+, CD8+CD45RO+). The decreases of CD11a and CD18 MFIs were accompanied by the decrease in adherent capacity of PBMCs to HUVECs. Spermine did not hinder cell activities or cell viability. Among 42 healthy volunteers (mean, 49.5 years old; from 26 to 69), blood spermine levels inversely correlated with the CD11a MFIs of cells in the lymphocyte region (r = −0.48; p = 0.001), but not with those in the monocyte region. The effects of spermidine seemed weaker than those of spermine, and blood spermidine levels had no correlation with CD11a MFIs of the lymphocyte region. Putrescine had no effect on the expressions of membrane molecules. Polyamines, especially spermine, decrease LFA-1 (CD11a/CD18) expression on human lymphocyte and adhesion capacity of PBMCs to HUVECs.

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“…, 1988a). High levels of ODC activity have been found during cell prolifer ation (O 'Brien and Diamond, 1977) and increased polyamines are required for certain growth regulated cellular functions (Holtta and Hovi, 1985;Seidenfeld et aI. , 1985).…”

mentioning

confidence: 99%

Modulation of Ornithine Decarboxylase mRNA following Transient Ischemia in the Gerbil Brain

Dempsey¹,

Carney

Kindy

1991

J Cereb Blood Flow Metab

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Summary: Ornithine decarboxylase (ODC) is the rate limiting enzyme that catalyzes the synthesis of poly amines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cere bral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient isch emia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which corre lates with increased ODC activity and polyamine synthe-The biochemical and physiological significance of polyamine biosynthesis in cellular growth has been well characterized in both prokaryotes and eukary otes. The polyamines have been shown to be asso ciated with cell proliferation, differentiation, and growth (Pegg and McCann, 1982;Pegg, 1986) Abbreviations used: CREB, cyclic AMP-responsive element binding protein; ODC, ornithine decarboxylase; SDS, sodium dodecyl sulfate; SSC, 3 M NaC1I0.3 M sodium citrate. 979sis. Increased ODC mRNA can be detected in the fore brain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfu sion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expres sion after ischemia. We conclude that the ischemia induced increase in ODC enzyme activity may be attrib uted in part to transcriptional activation of the ODC gene.

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Polyamine depletion results in impairment of polyribosome formation and protein synthesis before onset of DNA synthesis in mitogen-activated human lymphocytes

Cited by 33 publications

References 39 publications

Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA.

Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA.

Spermine, a Natural Polyamine, Suppresses LFA-1 Expression on Human Lymphocyte

Modulation of Ornithine Decarboxylase mRNA following Transient Ischemia in the Gerbil Brain

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