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PubMedDate not supplied

In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthritis patients.

OBJECTIVE: Several studies have documented increased levels of polyamines in rheumatoid arthritis (RA). We have suggested that one of the mechanisms of action of methotrexate (MTX) involves the inhibition of polyamine synthesis in lymphocytes. In this study, we sought to establish the inhibitory effect of MTX on polyamine synthesis and its specificity. METHODS: Polyamine levels were determined in stimulated RA lymphocytes incubated in vitro with MTX and compared to levels in lymphocytes incubated with hydrocortisone, D-penicillamine, or medium alone. Lymphocyte polyamine levels were correlated with IgM-rheumatoid factor (RF) synthesis. RESULTS: Incubation with MTX resulted in concentration-dependent decreased intracellular levels of spermidine and spermine, while putrescine levels were not affected. Addition of folinic acid or S-adenosyl-methionine (SAM) prevented this MTX-induced inhibition. Incubation with D-penicillamine or hydrocortisone had no significant effect on polyamine levels. There was a positive correlation between intracellular polyamine levels and the inhibition of IgM-RF synthesis by MTX. CONCLUSION: These data suggest that MTX inhibits the synthesis of spermidine and spermine in stimulated RA lymphocytes through inhibition of the SAM-dependent pathway. This inhibition may be related to the immune-modulating properties of MTX.

Anti-Inflammatory Agents↗
PubMed1997

Polyamines increase in the brain stem and cerebellum following labyrinthectomy.

The goal of this investigation was to test the hypothesis that unilateral damage to the vestibular end-organ (labyrinthectomy) stimulates polyamine synthesis in central vestibular neural structures that mediate the process of behavioral recovery (vestibular compensation). Pharmacological studies have shown that compensation can be altered by alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis. Because polyamines are important in regeneration, development and modulation of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors, which mediate vestibular synaptic plasticity, we investigated changes in polyamines in specific central vestibular structures after unilateral labyrinthectomy. The supernatant fraction of brain tissue homogenates was reacted with dansyl chloride. Dansylated polyamine derivatives were quantified in the vestibular nuclei, cerebellum, and inferior olive in both the control and the unilaterally labyrinthectomized guinea pig by high-performance liquid chromatography-fluorometric detection. No left-right differences in putrescine, spermidine, or spermine were detected in any brain parenchyma of controls. Polyamine imbalance, characterized by increased spermidine in the ipsilateral medial and lateral vestibular nuclei, was noted 12 and 24 h after unilateral labyrinthectomy (UL). In contrast, spermidine, spermine, and putrescine were elevated bilaterally in the cerebellum and inferior olive after UL. These biochemical changes may represent neuronal modifications to establish a balance between the vestibular nuclei after unilateral labyrinthectomy. Elucidation of the role of polyamines in central vestibular function and in vestibular compensation offers promise for the development of novel therapeutic strategies for treatment of vestibular disorders.

Analysis of Variance↗
PubMed1996

Neuromodulation by Mg2+ and polyamines of excitatory amino acid currents in rodent neurones in culture.

Excitatory amino-acid currents in rodent central neurones are mediated by the activation of glutamate receptors. Ionotropic types of the receptors are divided into alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors, and the former two are collectively called non-NMDA receptors. The NMDA receptor is modulated by a number of endogenous neuromodulators including Mg2+, polyamines, glycine and protons in extracellular solutions. Although it has been generally thought that each of the neuromodulators acts on a distinct site in the NMDA receptor, recent studies have revealed that these actions may be not necessarily independent of each other. The NMDA receptor response is not only inhibited but also potentiated by Mg2+, and the latter action is due to an interaction of a Mg2+ site with either glycine- or proton-binding site. In the presence of polyamines, a tonic inhibition by protons of the NMDA receptor response is relieved, resulting in a potentiation of the response. Alternatively, it has been recently revealed that there are some subtypes of non-NMDA receptors which are negatively modulated by polyamines in either extra- or intra cellular solutions. The difference in polyamine sensitivity among non-NMDA receptors is attributed to a distinction in their constituted subunits. The inhibition of non-NMDA receptor by intracellular polyamines results in inward rectification of the current-voltage relation which is not seen for polyamine-insensitive ones. This polyamine action is not mimicked by intracellular Mg2+.

Action Potentials↗
PubMedDate not supplied

Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte polyamine levels in rheumatoid arthritis: correlation with the clinical response and rheumatoid factor synthesis.

OBJECTIVE: Polyamines are increased in activated lymphocytes, including peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA), and are important in modulating immune-mediated cellular responses. In vitro studies have suggested that methotrexate (MTX) interferes with polyamine synthesis. This study evaluated the in vivo polyamine response to MTX compared to other anti-arthritic agents, and correlated it with the clinical and immunological response. METHODS: The polyamine content of PBL was determined in 14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints were counted monthly. RESULTS: Polyamines (spermine and spermidine) decreased by 55% at three months in the MTX group compared to 4% and 9% in the HCQ and prednisone groups, respectively (p < 0.01). However, group differences in the clinical and immunological response were not significant. In the MTX group there was a positive correlation between polyamine levels and the joint count. Such a correlation was not observed in the other groups. CONCLUSION: These data suggest that MTX interference with the polyamine pathway is not shared by prednisone and HCQ, and is associated with its beneficial effect in RA.

Adult↗
PubMed1997

The influence of polyamines synthesis inhibition on pancreas regeneration and phospholipase D activity after acute caerulein induced pancreatitis in rats. Biochemical and ultrastructural study.

The importance of polyamines in tissue growth and regeneration was shown. The involvement of phospholipase D (PLD) activity in pancreas recovery after acute pancreatitis (AP) was postulated. Thus, the aim of present study was to evaluate: the effect of polyamines synthesis inhibition on pancreas regeneration after AP and possible relationship between polyamines metabolism and PLD activity during recovery after AP. AP was induced by s.c. injection of caerulein (Cae.) in gelatin (12 micrograms/kg; t.i.d.) during 2 days. After AP inducion rats were treated with the irreversible inhibitor of polyamines synthesis alpha-difluoromethylornithine (DFMO) and/or putrescine or saline for 2, 7 and 14 days. Pancreatic weight, total protein, enzymes, nucleic acids contents were evaluated and ultrastructural examination was performed. Also pancreatic acini were prepared and loaded with [3H] myristic acid to measure 3H phosphatidic acid (PA), a marker of PLD activity. For in vitro study the pancreatic acini from healthy rats were preincubated with 1 mM DFMO and stimulated with Cae. AP results in pancreas destruction, followed by spontaneous recovery within 14 days. We found that treatment with DFMO during AP induction did not produce more severe tissue damage. However, when this treatment was prolonged (up to 14 days) during the recovery period after pancreatitis injury reduced the spontaneous regeneration. Microscopic examination showed also the more prominent signs of acinar cell injury in AP-DFMO treated rats vs. AP animals especially after 7 and 14 days of treatment. The signs of microscopic injury, lower pancreatic weight and RNA content in acute pancreatitis rats treated with DFMO during 14 days vs. control group correspond with the increased PLD activity observed after 7 and 14 days of treatment. PLD activity increased significantly also in healthy rats treated with DFMO already after 2 days and remained at significantly elevated level after 7 and 14 days of treatment vs. control. The obtained results indicate the involvement of polyamines in pancreas recovery after acute pancreatitis and in unspecified pancreas injury with concomitant increase of PLD activity. However the modulation/elevation of enzyme activity does not seem to be directly related to polyamines metabolism in the pancreas as the lack of DFMO effect on PLD activity in vitro study was found. The results suggest rather indirect modulatory influence of polyamines on intracellular signaling pathway.

Animals↗
PubMed1988

Chain-fluorinated polyamines as tumour markers. III. Determination of geminal difluoropolyamines and their precursor 2,2-difluoroputrescine in normal tissues and experimental tumours by in vitro and in vivo 19F NMR spectroscopy.

Treatment of laboratory animals bearing transplantable tumours with alpha-difluoromethylornithine, an inhibitor of ornithine decarboxylase, followed by 2,2-difluoroputrescine allows the partial replacement of the endogenous polyamines spermidine and spermine by their fluorine-containing analogs 6,6-difluorospermidine and 6,6-difluorospermine. Quantitative determination of the chain-fluorinated polyamines in excised tumor tissue by in vitro 19F NMR spectroscopy at 11.7 T gave results similar to those obtained by extraction and HPLC analysis. The NMR methods allowed the observation of several as yet unidentified geminal difluoropolyamine metabolites with a detection threshold as low as 1 nmole/g. Using a surface coil at 2.4 T, it was possible to detect in 10-20 min fluorinated polyamines in tumour, liver and bladder (urine) of mice in vivo at concentrations of the order of 50-100 nmol/g, i.e., when 2-5% of the natural polyamines have been replaced by their fluoro analogs. Since 6,6-difluorospermidine and 6,6-difluorospermine preferentially accumulate in tumours and specific tissues with enhanced polyamine metabolism, it is expected that these compounds may serve as probes for the application of 19F NMR methods for tumour diagnosis and therapy control. Since significant quantities of additional fluorine-containing polyamine metabolites were detected in some tissues, 19F NMR spectroscopy will contribute to our knowledge of polyamine metabolism in normal and tumour tissue.

Animals↗
PubMed2006

Polyamine deficiency leads to accumulation of reactive oxygen species in a spe2Delta mutant of Saccharomyces cerevisiae.

We have previously shown that polyamine-deficient Saccharomyces cerevisiae are very sensitive to incubation in oxygen. The current studies show that, even under more physiological conditions (i.e. growth in air), polyamine-deficient cells accumulate reactive oxygen species (ROS). These cells develop an apoptotic phenotype and, after incubation in polyamine-deficient medium, die. To show a specific effect of polyamines on ROS accumulation, uncomplicated by any effects on growth, spermine was added to spermidine-deficient spe2Delta fms1Delta cells, since spermine does not affect the growth of this strain. In this strain, spermine addition caused a marked, but not complete, decrease in the accumulation of ROS and a moderate protection against cell death. In other experiments with polyamine-deficient cells containing plasmids that overexpress superoxide dismutases (SOD1, SOD2), ROS decreased but with only a partial protection against cell death. Polyamine-deficient cells incubated anaerobically show markedly less cell death. These data show that part of the function of polyamines is protection of the cells from accumulation of ROS.

Apoptosis↗
PubMed2001

Involvement of polyamines in B cell receptor-mediated apoptosis: spermine functions as a negative modulator.

The B cell lymphoma WEHI231 has been used as a model for studying clonal deletion of B cells on the basis of its ability to undergo growth arrest and apoptosis by B cell antigen receptor (BCR) cross-linking. To comprehensively analyze the genes involved in BCR-mediated apoptosis, we applied the technique of serial analysis of gene expression (SAGE) to WEHI231. Comparison of expression patterns revealed that BCR cross-linking caused coordinate changes in the expression of genes involved in polyamine metabolism. Polyamines are ubiquitous compounds required for cell proliferation and homeostasis. The coordinate expression of the polyamine-related genes was confirmed by semiquantitative reverse transcriptase-polymerase chain reaction analysis. During apoptosis, the genes involved in polyamine biosynthesis were downregulated, whereas those involved in polyamine catabolism were upregulated, suggesting that intracellular polyamines play a role in BCR-mediated apoptosis. Levels of intracellular putrescine, spermidine, and spermine were reduced after BCR cross-linking. These effects were prevented by concurrent CD40 stimulation, which blocked BCR-mediated apoptosis. Furthermore, addition of spermine could repress the BCR-mediated apoptosis by attenuating the mitochondrial membrane potential (Deltapsim) loss and activation of caspase-7 induced by BCR signaling. These findings strongly suggest that polyamine regulation is involved in apoptosis during B cell clonal deletion.

Animals↗
PubMed2005

Mechanism of polyamine tolerance in yeast: novel regulators and insights.

Polyamines are small charged molecules essential for various cellular functions, but at high levels they are cytotoxic. Two yeast kinases, SKY1 and PTK2, have been demonstrated to regulate polyamine tolerance. Here we report the identification and characterization of additional genes involved in regulating polyamine tolerance: YGL007W, FES1 and AGP2. Deletion of YGL007W, an open reading frame located within the promoter of the membrane proton pump PMA1, decreased Pma1p expression. Deletion of FES1 or AGP2 resulted in reduced polyamine uptake. While high-affinity spermine uptake was practically absent in agp2Delta cells, fes1Delta cells displayed only reduced affinity towards spermine. Despite the reduced uptake, the resistant strains accumulated significant levels of polyamines and displayed increased ornithine decarboxylase activity, suggesting reduced polyamine sensing. Interestingly, fes1Delta cells were highly sensitive to salt ions, suggesting different underlying mechanisms. These results indicate that mechanisms leading to polyamine tolerance are complex, and involve components other than uptake.

Amino Acid Transport Systems↗
PubMed2000

Putrescine and Silver Nitrate Influences Shoot Multiplication, In Vitro Flowering and Endogenous Titers of Polyamines in Cichorium intybus L. cv. Lucknow Local.

The influence of putrescine (Put) and AgNO(3) on shoot multiplication, in vitro flowering and endogenous titers of polyamines in Cichorium intybus L. cv. Lucknow local was investigated. Exogenous administration of Put at a concentration of 40 mM resulted in maximum tissue response in terms of shoot numbers (34.6 +/- 2.61) and shoot lengths (7.6 +/- 0.57 cm) on MS media supplemented with 2-iP (2.0 mg L(-1)) and GA(3) (0.5 mg L(-1)) as observed on the 35(th) day. Exogenous application of 40 µM AgNO(3) resulted in maximum shoot number (36.8 +/- 2.63) and shoot lengths (7.9 +/- 0.76 cm) on day 35 on the same media. Endogenous titers of conjugated spermidine decreased sharply from day 7-21, whereas endogenous conjugated spermine levels peaked on day 28 (1265 +/- 94.9 nmoles g(-1) FW), after treatment with 40 mM Put. Whereas, AgNO(3) (40 µM) fed samples resulted in higher titers of endogenous conjugated spermine (1405 +/- 105.6 nmoles g(-1) FW, 3.62 fold over control) on day 14. All other treatments showed decreasing endogenous levels during the whole culture period. Both Put (40 mM) and AgNO(3) (40 µM) resulted in floral initiation and floral development on day 28 and 14 (3.76 +/- 0.16, 4.2 +/- 0.21 flowers per shoot apices), respectively. To investigate the role of Put (40 mM) and AgNO(3) (40 µM) on morphogenetic response and endogenous conjugated polyamine titers in shoots of chicory, polyamine inhibitors (DFMA and DFMO) were used. The morphogenetic response and the endogenous conjugated pool of polyamines were diminished in DFMA and DFMO treatments, but could be restored by addition of Put (40 mM) and AgNO(3) (40 µM). Under exogenous Put feeding, ethylene production was reduced in shoot cultures of chicory. This study shows for the first time the influence of polyamines on multiple shoot initiation from axillary buds of C. intybus L. cv. Lucknow local and also indicates the promotive effect of Put and AgNO(3) on autoregulation of polyamine biosynthesis, thereby regulating in vitro flowering, the endogenous pool of polyamines and shoot multiplication.

Journal Article↗
PubMed1980

A preliminary study of polyamines in the bone-marrow plasma of adult patients with leukemia.

Polyamines (mainly putrescine, spermidine, and spermine) whose biosynthesis is a prerequisite for cell proliferation, are potential indicators of malignant growth. To investigate the mechanism of alterations of polyamine levels in physiological fluids in human cancer, polyamine levels of bone-marrow plasma from adult patients with leukemia were studied. Significant correlations were observed between bone-marrow cellularity and spermidine, between peripheral white blood cell counts and spermidine and spermine, and between absolute blast count and spermidine and spermine among untreated patients with acute leukemia. Untreated patients with chronic leukemia showed significantly elevated levels of polyamines relative to untreated patients with acute leukemia, indicating a higher turnover of bone-marrow cells in chronic leukemia than in acute leukemia. Chemotherapy-treated patients with acute leukemia who were in remission or who did not respond to the agent showed low polyamine levels. Patients who showed a destruction of tumor cell during chemotherapy gave high levels of polyamines. Overall, these studies indicate that elevated polyamine levels are markers of cell death.

Adult↗
PubMed1996

Differential post-transcriptional control of ornithine decarboxylase and spermidine-spermine N1-acetyltransferase by polyamines.

Ornithine decarboxylase (ODC) and spermidine/ spermine N1-acetyltransferase (SSAT) are short-lived polyamine enzymes with rate-limiting roles in controlling polyamine biosynthesis and catabolism, respectively. We have found that treatment of MALME-3M human melanoma cells for 6 h with 10 micrograms/ml cycloheximide (CHX) increases ODC and SSAT mRNA 6-9-fold. When cells containing CHX-induced SSAT mRNA were washed and post-incubated for an additional 6 h in drug free media, enzyme activity increased only 2-fold above that in untreated cells despite the > 6-fold increase in accumulated mRNA. Inclusion of 10 microM spermine or spermidine in the post-incubation medium increased SSAT activity approximately 7-fold without further elevating SSAT mRNA levels. This indicates post-transcriptional regulation which, due to the similarity between polyamine-mediated increases in SSAT activity and available mRNA, probably occurs at the level of mRNA translation. In contrast to the SSAT response, polyamines markedly reduced ODC activity (but not mRNA) to one sixth that in cells not exposed to polyamines. The findings illustrate how via post-transcriptional mechanisms, shifts in intracellular polyamine pools can simultaneously and differentially regulate polyamine biosynthesis and catabolism. It is hypothesized that these post-transcriptional responses enable cells to rapidly and sensitively control intracellular spermidine and spermine pools.

Acetyltransferases↗
PubMed1991

Effects of elevated CO2 concentration on the polyamine levels of field-grown soybean at three O3 regimes.

Effects of increased ozone (O3) and carbon dioxide (CO2) on polyamine levels were determined in soybean (Glycine max L. Merr. cv. Clark) grown in open-top field chambers. The chamber treatments consisted of three O3 regimes equal to charcoal filtered (CF), non-filtered (NF), and non-filtered plus 40 nl litre(-1) O3 and CO2 treatments equal to 350, 400 and 500 microl litre(-1) for a total of nine treatments. Leaf samples were taken at three different times during the growing season. Examination of growth and physiological characteristics, such as photosynthesis, stomatal resistance, and shoot weight, revealed that increasing CO2 ameliorated the deleterious effects of increased O3. Results from the initial harvest, at the pre-flowering growth stage (23 days of treatment), showed that increasing O3 at ambient CO2 caused increases in putrescine (Put) and spermidine (Spd) of up to six-fold. These effects were lessened with increased CO2. Elevated CO2 increased polyamines in plants treated with CF air, but had no effect in the presence of ambient or enhanced O3 levels. Leaves harvested during peak flowering (37 days of treatment) showed O3-induced increases in Put and Spd at ambient CO2 concentrations. However, increased CO2 levels inhibited this response by blocking the O3-induced polyamine increase. Leaves harvested during the pod fill stage (57 days of treatment) showed no significant O3 or CO2 effects on polyamine levels. Our results demonstrate that current ambient O3 levels induce the accumulation of Put and Spd early in the growing season and that further increases in O3 could result in even greater polyamine increases. These results are consistent with a possible antiozonant function for polyamines. The ability of increased CO2 to protect soybeans from O3 damage, however, does not appear to involve polyamine accumulation.

Journal Article↗
PubMed1995

Polyamine uptake by a rodent filariid, Acanthocheilonema viteae (Nematoda: Filarioidea).

Helminth parasites lack the capacity to synthesize polyamines de novo. With the view to characterise alternative pools for the replenishment of polyamines, uptake of spermidine and spermine, were studied in Acanthocheilonema viteae, a parasite known to infect rodents. Motile worms recovered from the subcutaneous tissues of experimentally infected Mastomys natalensis were incubated in vitro with radiolabelled polyamines for the uptake assays. A time-dependent, temperature-sensitive, energy-requiring and saturable-uptake of the polyamines was observed. Male worms exhibited better uptake than the females and spermidine influx occurred at a higher rate than for spermine. A marginal competition of spermine with spermidine uptake and vice-versa was noticed while putrescine did not compete with uptake of either polyamines. Methyl-glyoxal-bis-guanyl hydrazone and Berenil caused significant inhibition of spermidine as well as spermine uptake. Subcutaneous tissues of A. viteae infected animals exhibited markedly higher levels of polyamines compared with the tissues obtained from healthy animals. Filarial worms are thus equipped with multiple polyamine transport systems which may aid their growth and survival within the host.

Animals↗
PubMed1999

Effects of a high soy protein diet on intestinal polyamines and ornithine decarboxylase activity in rats.

This study was performed to determine whether intestinal luminal polyamine concentrations are affected by a high soy protein diet when compared with a high casein diet or a normoprotein casein diet. We also determined the effects of these diets, with differences in polyamines content, on mucosal polyamines and ornithine decarboxylase (ODC) activity to assess cell proliferation. Three groups of eight male Wistar rats were fed either a 50% soy protein diet, a 50% casein diet, or an 18% casein diet as a control. After 4 weeks of feeding, both intestinal content and mucosa were recovered. Polyamines were assayed by high performance liquid chromatography. ODC activity was measured by the release of (14)CO(2) from (14)C-L-ornithine. Luminal putrescine and cadaverine concentrations were higher in the jejunum than in the ileum, suggesting an absorptive process. The highest concentrations of intestinal polyamines were observed in rats fed the soy protein diet (P < 0.05). Only minor differences were observed in mucosal polyamines according to the diets. ODC activity was also higher in the intestinal mucosa of rats fed the high soy protein diet (P < 0.05). These results suggest that intestinal luminal polyamine concentrations and ODC activity are modulated by the dietary protein source.

Journal Article↗
PubMed1999

Regulation of polyamine synthesis and transport by retinoic acid and epidermal growth factor in cultured adult rat type II pneumocytes.

During injury of lung epithelial cells, the type II pneumocyte proliferates and differentiates into a type I pneumocyte to restore the epithelium. Polyamines, which constitute a family of small organic polycations, are required for this process of cell repair. Because retinoic acid (RA) and epidermal growth factor (EGF) also are involved, the purpose of this research was to determine their effect on polyamine transport and synthesis in cultured type II pneumocytes. Rat type II pneumocytes were isolated, cultured overnight, and treated with RA and/or EGF for 24 hours. Polyamine transport was determined by [(3)H]spermidine uptake, and polyamine synthesis was assessed by the activity of the initial rate-limiting enzyme ornithine decarboxylase. EGF (100 ng/mL) significantly increased spermidine transport, but RA did not. At low concentrations of spermidine (2 microM), the combined effect of RA and EGF on spermidine transport was additive. Both EGF (25 ng/mL) and RA (1 microM) increased polyamine synthesis, and cotreatment resulted in an additive effect (a fourfold increase over the control). We also found that ornithine decarboxylase activity is greatly diminished in the presence of tyrphostin B56, which is a specific inhibitor for the tyrosine kinase of the EGF receptor, suggesting that polyamine synthesis within the type II pneumocyte may depend on activation of tyrosine kinase of the EGF receptor. These results indicate that RA and EGF increase the availability of polyamines, which may be important in the lung cell repair process.

Journal Article↗
PubMed1999

Enhanced uptake of [3H] spermidine by 9L rat brain tumors after direct intratumoral infusion of inhibitors of enzymes of the polyamine biosynthetic pathway.

We have been exploring the feasibility of delivering ionizing radiation to brain tumor cells by using tritium labeled polyamines. Polyamines are taken up preferentially by dividing cells and form noncovalent bonds with DNA. Their uptake can be enhanced by drugs which deplete endogenous polyamines. To test this in vivo, 9L cells were implanted in the striatal region of the brain in male Fisher 344 rats. Osmotic pumps containing trace amounts of [3H] spermidine or [3H] putrescine with either difluoromethylornithine or combinations of 3 inhibitors of enzymes of the polyamine biosynthetic pathway were implanted subcutaneously and were connected to intratumoral cannulas. After 14-16 days the brains were removed and sliced in the coronal plane. The diameters of the tumors were measured and tumor tissue was dissected from each slice, weighed and lysed for scintillation counting. It was found that difluoromethylornithine enhanced the uptake of [3H] putrescine while a combination of inhibitors of enzymes of the polyamine biosynthetic pathway enhanced the uptake of [3H] putrescine and [3H] spermidine producing a localized region of radioactivity in the 9L tumor. It is estimated that if the [3H] polyamines were at higher specific activity (commercially available), instead of the trace dose given here, the [3H] polyamine uptake would be sufficient to kill 9L tumor cells within a 2 to 3 week period.

Adenosylmethionine Decarboxylase↗
PubMed2001

The effect of AOA on ethylene and polyamine metabolism during early phases of somatic embryogenesis in Medicago sativa.

Changes in the levels of ethylene, 1-aminocyclopropane-1-carboxylic acid (ACC), 1-(malonylamino)cyclopropane-1-carboxylic acid (MACC) and polyamines were simultaneously investigated during the early phases of alfalfa somatic embryogenesis. These included the period of induction and subculture of callus, and 3- and 7-day suspension cultures for the induction of somatic embryogenesis. The polyamines contained in the embryogenic callus were found to include putrescine (Put), spermidine (Spd) and spermine (Spm), but the level of Spm was much less than that of Put and Spd. There was a dramatic increase in MACC after induction of embryogenesis, and ACC levels were lower in somatic embryos than in embryogenic callus. Induction of embryogenesis for 3 days increased the levels of ACC and polyamines to a maximum level, and these then reduced as the embryogenesis proceeded. The ratios of Put/Spd and ACC/MACC were decreased during the induction. This indicated that both high levels of ACC and polyamines might be a prerequisite for early differentiation during the induction of the embryogenesis. Thus, there appears not to be competition between polyamine biosynthesis and ethylene biosynthesis at least during the induction of somatic embryogenesis, because both the polyamines and ACC were simultaneously increased during the induction period. Conversion of ACC into MACC and the maintenance of a relatively high level of polyamines, especially Spd, appear to be important for further development of the embryos. When aminooxylvinylglycine (AOA) was added at the initiation of the callus subculture, it had no significant effect on the callus growth, the ethylene production and ACC level of the callus. However, AOA increased the numbers of the embryos accompanying an increase in Spd level and S-adenosylmethionine decarboxylase (SAMDC) activity. Thus, the AOA effect could be associated with Spd increase rather than with the effect of ethylene biosynthesis.

Journal Article↗