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Results for “Biogenic Polyamines”

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PubMed1999

Influence of polyamines on DNA binding of heat shock and activator protein 1 transcription factors induced by heat shock.

Polyamine depletion, obtained in FAO cells with specific inhibitors of biosynthetic enzymes, prevents or decreases the accumulation of hsp 70 mRNA following heat shock [Desiderio et al., Hepatology 24 (1996) 150-156]. The present study shows that under conditions of spermidine depletion caused by alpha-difluoromethylornithine, the DNA binding capacity of the transcription factor HSF induced by heat shock undergoes a severe and prompt deactivation. Replenishment of the spermidine pool before heat shock re-establishes the DNA binding activity of HSF and the inducibility of hsp 70 mRNA. Similar to HSF, but with a different time-course, the DNA binding of the transcription factor AP-1 activated by heat shock is also impaired in spermidine-depleted cells and reversed by exogenous spermidine. STAT3 provides an example of a transcription factor slightly activated by heat shock but insensitive to polyamine decrease.

Animals↗
PubMed1991

Polyamine oxidase activity and concentration of polyamines in tissues and serum of hamsters with transplantational pigmented melanoma IC-Sofia.

The activity of polyamine oxidase (PAO) participating in the intracellular catabolitic interconversion of the polyamines and the total concentration of polyamines in some tissues of hamsters with transplantational pigmented melamoma IC-Sofia were studied. The experiments were carried out on day 0, as well as on the 11th, 15th, 21st and 27th day after the tumor transplantation. The PAO activity and the polyamine concentration were determined in tumor tissue (with the exception of day 0), in the liver, kidneys, lung and serum (without PAO). A gradual decrease of the PAO activity and a marked rise in the total concentration of polyamines were observed in the growing tumor. In the remaining tissues the PAO activity initially rose slightly until the 15th day, then dropped, whereas the polyamine concentration increased all the time. The dynamics of the enzyme activity and the polyamine concentration were most pronounced in the lung. Tumor growth was not accompanied by changes in the polyamine concentration in the serum.

Animals↗
PubMedDate not supplied

[Immunosuppressive action of polyamines in patients with chronic myeloid leukemia].

To assess the role of polyamines in the mechanism of immunosuppression in patients with chronic myeloid leukemia (CML), polyamines levels were measured in the urine and blood, polyamines reactivity was investigated in 113 CML patients in correlation with the process aggression. In patients with aggressive CML (23 subjects) and large tumor mass the above concentrations were significantly higher than in patients with less severe CML run (90 subjects). There were also parallels between polyamines concentrations in the biological media and the patient's immunoreactivity. This suggests involvement of polyamines in immunosuppression observed in CML.

Biogenic Polyamines↗
PubMed1992

Polyamines in liver and their influence on chromatin condensation after 17-beta estradiol treatment of Atlantic salmon.

Atlantic salmon (Salmo salar) were treated with 17-beta estradiol to induce vitellogenin synthesis in liver. This led to an increase in liver wet weight and total DNA. After incubation with micrococcal nuclease (EC 3.1.31.1) less soluble chromatin was obtained from nuclei of the estradiol treated than the control fish, but active gene regions were solubilized by the nuclease. Thus, in the estradiol treated fish soluble mononucleosomes contained hybridizable vitellogenin gene sequences. As a result of estradiol treatment the content in total liver of putrescine rose 3-fold, that of spermidine 2-fold, while spermine was unchanged. In muscle no significant changes were observed. The regulatory functions of polyamines during gene expression were investigated by binding (14C)spermine to isolated liver nuclei depleted of endogenous polyamines. The number of binding sites was higher in nuclei of estradiol treated than control fish. (14C)spermine associated preferentially with micrococcal nuclease insensitive chromatin. Thus, the high content of putrescine and spermidine in liver supported the view of polyamine accumulation in proliferating tissues. The preferential binding to condensed chromatin indicated a stabilizing effect of polyamines on the organization of inactive chromatin structures.

Animals↗
PubMed1989

Polyamine transport systems in the LLC-PK1 renal epithelial established cell line.

LLC-PK1 cells were brought to a quiescent state by treatment with DL-2-difluoromethylornithine (DFMO), a specific inhibitor of L-ornithine decarboxylase (ODC). The inhibition of ODC, which is the key enzyme for polyamine synthesis, strongly reduced the cellular content of putrescine and spermidine. The cells resumed DNA-synthesis followed by mitosis when exogenous putrescine was added. DFMO treatment strongly stimulated the putrescine uptake capability. A kinetic analysis of the initial uptake rates revealed a saturable Na+-dependent and a saturable Na+-independent pathway on top of non-saturable diffusion. The stimulation by DFMO was exclusively due to an effect on the Vmax values of the saturable pathways. The Na+-dependent transporter had a higher affinity for putrescine (apparent Km = 4.7 +/- 0.7 microM) than the Na+-independent transporter (apparent Km = 29.8 +/- 3.5 microM). As a consequence, although the latter transporter had a higher Vmax, the Na+-dependent transport was more important at a physiological putrescine concentration. Putrescine uptake by both transporters was inhibited with similar relative affinities by spermidine, spermine as well as by the antileukemic agent, methylglyoxal bis(guanylhydrazone), but not by amino acids. The activity of the Na+-dependent transporter was very much dependent on SH-group reagents, whereas the Na+-independent transporter was not affected. Both transporters were inhibited by metabolic inhibitors and by ionophores but the Na+-dependent transporter was affected to a greater extent. For both transporters there was a down-regulation in response to exogenous putrescine. This suggests that the polyamine transporters in LLC-PK1 are adaptively regulated and may contribute to the regulation of the cellular polyamine level and cellular proliferation.

Animals↗
PubMed2001

Determination of polyamines in human saliva by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method for the determination of polyamines (spermine, spermidine and putrescine) in human saliva was developed. This method is based on pre-column derivatization with o-phthaldialdehyde (OPA). The derivatives were separated on a Nucleosil ODS column (250x4.6 mm I.D.; 5 microm). The gradient elution was performed with two mobile phases A (water) and B (methanol) at a flow rate of 0.8 ml/min. The column eluate was monitored by fluorescence detection (excitation, 360 nm; emission, 510 nm). The within- and between-assay coefficients of variation for all the compounds were below 5%. The detection limits for spermine, spermidine and putrescine were 0.04, 0.05 and 0.06 nmol/ml, respectively. The recovery was greater than 90%. Our analytical technique requires neither preliminary extraction with an organic solvent, nor long multi-step procedures. For saliva samples, this is a simple, rapid and highly reproducible method that can be easily applied to the routine determination of salivary polyamines, whose levels increase early in several pathological conditions.

Biogenic Polyamines↗
PubMed2002

Cytotoxic effects of the polyamine oxidase inactivator MDL 72527 to two human colon carcinoma cell lines SW480 and SW620.

N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) was considered to be a selective inactivator of FAD-dependent tissue polyamine oxidase. Recently MDL 72527 was reported to induce apoptosis in transformed hematopoietic cells through lysosomotropic effects. Since it is the only useful inhibitor of polyamine oxidase available at present, the re-evaluation of its properties seemed important. Human colon carcinoma-derived SW480 cells and their lymph node metastatic derivatives (SW620) were chosen for our study because they differ in various aspects of polyamine metabolism but have similar polyamine oxidase activities. MDL 72527 inhibited cell growth in a concentration-dependent manner, depleted intracellular polyamine pools, and caused the accumulation of N1-acetyl derivatives of spermidine and spermine. SW620 cells were more sensitive to the drug than were SW480 cells. At 150 micromol/L MDL 72527, SW620 cells accumulated in S-phase of the cell cycle, showed decreased polyamine transport rate, and showed no increase of polyamine N1-acetyltransferase activity. In contrast, SW480 cells were not arrested in a particular phase of the cell cycle, showed enhanced polyamine uptake, and showed a mild induction of acetyltransferase. The results suggest that MDL 72527 retains its value as a selective tool in short-term experiments only at concentrations not exceeding those necessary for the inactivation of polyamine oxidase. At concentrations above 50 micromol/L and at exposure times longer than 24 h, it may derange cell functions nonspecifically, and thus blur the results of studies intended to elucidate polyamine oxidase functions.

Biogenic Polyamines↗
PubMed2003

Polyamines reduce paraquat-induced soxS and its regulon expression in Escherichia coli.

Polyamines, ubiquitous polycationic compounds, are involved in many cellular responses and relieve paraquat-induced cytotoxicity in Escherichia coli. We constructed a new E. coli mutant strain, JIL528, which is deficient in the biosynthesis of both putrescine and spermidine, to examine the physiological role of polyamines under oxidative stress caused by paraquat. Putrescine and spermidine downregulate the expression of soxS induced by paraquat in a concentration-dependent manner. The product of SoxS is a key regulator governing cellular responses against oxidative stress in E. coli. The downregulation of soxS expression by polyamines was not shown in the soxR mutant background. Glucose-6-phosphate dehydrogenase (G6PDH; encoded by zwf) and manganese-containing superoxide dismutase (Mn-SOD; encoded by sodA) activities induced by paraquat were decreased by exogenous polyamines. The induction of the zwf expression by paraquat was also decreased by exogenous polyamines. The polyamine-deficient mutant strain JIL528 showed a higher soxS expression than its parent polyamine-proficient wild type BW1157, on exogenous supplementation of paraquat concentrations below 1 micromol/L. While the growth rate of the mutant was decreased, soxS expression was increased in a concentration-dependent manner above 0.01 micromol/L of paraquat. In contrast, growth inhibition of the mutant by paraquat was relieved, and soxS was no longer induced by exogenous putrescine (1 mmol/L). In conclusion, polyamines protect against paraquat-induced toxicity but downregulate soxS expression, suggesting that the protective role of polyamines against oxidative damage induced by paraquat results in soxS downregulation.

Biogenic Polyamines↗
PubMed2004

Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice.

Tea polyphenolic constituents induce apoptosis in cancer cells but not in normal cells. To study the mechanism of this selective effect, we used the ornithine decarboxylase (ODC)/Ras double transgenic mouse model that develops spontaneous skin tumors due to over-expression of ODC and a v-Ha-ras transgene. Administration of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in the drinking water significantly decreased both tumor number and total tumor burden compared with untreated ODC/Ras mice without decreasing the elevated polyamine levels present in the ODC/Ras mice. EGCG selectively decreased both proliferation and survival of primary cultures of ODC over-expressing transgenic keratinocytes but not keratinocytes from normal littermates nor ras-infected keratinocytes. This decreased survival was due to EGCG-induced apoptosis and not terminal differentiation. Moreover, in skin from EGCG-treated ODC transgenic mice, caspase 3 (active form) was detected only in epidermal cells that possess very high levels of ODC protein. Since most transformed cells and tumor tissue possess higher levels of polyamines compared with normal cells or tissue, our data suggest that the elevated levels of polyamines in tumor cells sensitize them to EGCG-induced apoptosis. These results suggest that EGCG may be an effective chemopreventive agent in individuals with early, pre-neoplastic stages of cancer having higher levels of polyamines.

Animals↗
PubMed2001

Changes in polyamines, auxins and peroxidase activity during in vitro rooting of Fraxinus angustifolia shoots: an auxin-independent rooting model.

Among shoots of Fraxinus angustifolia Vahl raised in vitro, 76% rooted after culture on root induction medium for 5 days in darkness followed by culture on root expression medium for 15 days in light. The addition of 20.7 microM indole-butyric acid (IBA) to the root induction medium did not significantly increase the rooting percentage (88%). Putrescine, spermidine, cyclohexylamine (CHA) and aminoguanidine (AG) enhanced rooting up to 100% (98.66% for AG), when applied during root induction in the absence of IBA, otherwise these compounds inhibited rooting, as did spermine and difluoromethylornithine (DFMO) + difluoromethylarginine (DFMA). The root induction phase was characterized by a temporary increase in endogenous free indole-acetic acid (IAA) and putrescine concentrations during root induction, whereas the root expression phase was characterized by increased peroxidase activity and low concentrations of polyamines. These changes were specifically associated with the rooting process and did not depend on the presence of exogenous IBA, because application of exogenous IBA enhanced the amount of IAA in the cuttings but did not affect rooting or the pattern of changes in polyamines and peroxidase. The effects of CHA, AG and DFMO + DFMA on endogenous concentrations of auxins and polyamines highlight the close relationship between the effects of IAA and putrescine in root induction and suggest that polyamine catabolism has an important role in root formation and elongation.

Biogenic Polyamines↗
PubMed1992

Polyamines in nerve terminals and secretory granules isolated from neurohypophyses.

In isolated nerve terminals from ox neurohypophyses the following concentrations of polyamines [pmol (microgram protein)-1 (mean +/- SEM)] were found: spermine: 2.07 +/- 0.14 (n = 3), spermidine: 0.22 +/- 0.01 (n = 4), putrescine: 0.20 +/- 0.01 (n = 4). In secretory granules isolated from the same tissue, the concentrations were: spermine: 0.57 +/- 0.02 (n = 3), spermidine: 0.07 +/- 0.04 (n = 3), putrescine: 0.13 +/- 0.04 (n = 3). After incubation of isolated nerve terminals with the polyamines, they were taken up as a function of time and concentration, approaching saturation at high concentrations. The kinetic parameters of their synthesizing enzyme, ornithine decarboxylase, in ox neurohypophyseal nerve terminals (apparent Km 0.75 mM and Vmax 22.5 pmol mg protein-1 h-1) were comparable to those previously found in cerebral cortex of rats. When isolated, hemilobes from rat neurohypophyses were incubated in a medium which contained spermidine (5 mM), and were stimulated by 56 mM K+, release of vasopressin was smaller than in control experiments. However, after removal of spermidine and after restimulation, 50 min after initial stimulation, the release was significantly elevated. It is suggested that polyamines may take part in modulation of vasopressin release.

Animals↗
PubMed1996

Polyamines decrease Escherichia coli outer membrane permeability.

The permeability of the outer membranes of gram-negative bacteria to hydrophilic compounds is mostly due to the presence of porin channels. We tested the effects of four polyamines (putrescine, cadaverine, spermidine, and spermine) on two processes known to depend on intact porin function: fluxes of beta-lactam antibiotics in live cells and chemotaxis. In both cases, inhibition was observed. Measurements of the rate of permeation of cephaloridine and of chemotaxis in swarm plates and capillary assays were used to determine the concentration dependence of this modulation. The effective concentration ranges depended on the nature of the polyamine and varied from submillimolar for spermine to tens of millimolar for cadaverine. Both OmpC and OmpF porins were inhibited, although the effects on OmpC appeared to be milder. These results are in agreement with our observations that polyamines inhibit porin-mediated ion fluxes in electrophysiological experiments, and they suggest that a low-affinity polyamine binding site might exist in these porins. These results reveal the potential use of porins as targets for blocking agents and suggest that polyamines may act as endogenous modulators of outer membrane permeability.

Biogenic Polyamines↗
PubMed2000

Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets.

This study was conducted to determine a role for cortisol in regulating intestinal ornithine decarboxylase (ODC) activity and to identify the metabolic sources of ornithine for intestinal polyamine synthesis in suckling pigs. Thirty-two 21-day-old suckling pigs were randomly assigned to one of four groups with eight animals each and received daily intramuscular injections of vehicle solution (sesame oil; control), hydrocortisone 21-acetate (HYD; 25 mg/kg body wt), RU-486 (10 mg/kg body wt, a potent blocker of glucocorticoid receptors), or HYD plus RU-486 for two consecutive days. At 29 days of age, pigs were killed for preparation of jejunal enterocytes. The cytosolic fraction was prepared for determining ODC activity. For metabolic studies, enterocytes were incubated for 45 min at 37 degrees C in 2 ml of Krebs-bicarbonate buffer (pH 7.4) containing 1 mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U-(14)C]glutamine, or 1 mM [U-(14)C]proline plus 1 mM glutamine. Cortisol administration increased intestinal ODC activity by 230%, polyamine (putrescine, spermidine, and spermine) synthesis from ornithine and proline by 75-180%, and intracellular polyamine concentrations by 45-83%. Polyamine synthesis from arginine was not detected in enterocytes of control pigs but was induced in cells of cortisol-treated pigs. There was no detectable synthesis of polyamines from glutamine in enterocytes of all groups of pigs. The stimulating effects of cortisol on intestinal ODC activity and polyamine synthesis were abolished by coadministration of RU-486. Our data indicate that an increase in plasma cortisol concentrations stimulates intestinal polyamine synthesis via a glucocorticoid receptor-mediated mechanism and that proline (an abundant amino acid in milk) is a major source of ornithine for intestinal polyamine synthesis in suckling neonates.

Animals↗
PubMed2006

Role of polyamines derived from arginine in differentiation and proliferation of human blood cells.

L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine and is essential for the differentiation and proliferation of blood cells, although the precise biological role of L-arginine is unclear. We have recently reported that the depletion of L-arginine in cultured medium prevented both proliferation and differentiation of blood cells (Shima et al., Blood First Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of L-arginine in the cells is polyamine that associates with cell differentiation and proliferation, the effects of L-arginine on the human K562 cell line and human cord blood-derived CD34 positive cells were investigated by focusing on polyamines such as putrescine, spermidine, and spermine in the present study. When polyamines were added to the culture medium in the absence of L-arginine, the cells did not grow or differentiate well. However, when intracellular polyamines were depleted using ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), the proliferation and differentiation of K562 cells to erythrocytes were reduced even in the presence of L-arginine. Moreover, in the presence of DFMO, cell differentiation and proliferation were recovered by the addition of putrescine or spermidine in the presence of L-arginine. Accordingly, it was demonstrated that polyamines are essential for the proliferation and differentiation of the blood cells as the metabolites of L-arginine and the externally added polyamines are also effective by being taken up through polyamine transporter.

Antigens, CD34↗