Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polyamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1980

Possible role of polyamines in the function of brown adipose tissue.

In order to ascertain possible involvement of polyamines in the physiological regulation of brown fat function, effect of temperature acclimation on the polyamine contents of this tissue and effects of polyamines on the noradrenaline-induced thermogenesis is isolated brown adipocytes were investigated in rats. Daily urinary excretion of polyamines measured collectively for spermidine and spermidine per body weight was decreased in heat acclimation and increased in cold acclimation. Polyamine concentrations per fresh weight of brown fat showed extremely low values compared with those of other tissues previously reported. Putrescine and spermidine contents per fat-free dry matter of brown fat were decreased in cold acclimation, but were not affected in heat acclimation. Spermidine and spermine inhibited the noradrenaline-induced thermogenesis of brown adipocytes dose-dependently. These results suggest that polyamines regulate the heat production of brown adipose tissue in an inhibitory way and cold acclimation potentiates heat production of this tissue by reducing polyamine levels.

Acclimatization↗
PubMed1997

[Changes in tissue and blood polyamines during N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinogenesis in rats].

BACKGROUND: Polyamine are recognized as cell growth factors. We studied in order to determine whether alterations in the levels of tissue and blood polyamines were useful biochemical markers for bladder tumor. METHODS: The concentrations of three polyamines, diamine, spermidine and spermine, in urinary bladder and blood were determined during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in male F344 rats. At 5 weeks of age, rats were given 0.05% BBN in the drinking water for 20 weeks. RESULTS: BBN induced bladder hyperplasia in 4 of 5 rats at 8 weeks, papillomas in 2 of 5 rats at 12 weeks, and transitional cell carcinoma in all the rats by 20 weeks. The levels of total polyamine in both bladder and blood of the rats during 12-20 weeks were significantly higher than those of the control animals given water alone. The elevation of total polyamine was mainly due to the increase of spermidine of the three polyamines, which was coincident with the incidence of bladder tumors. CONCLUSION: The results indicated that the polyamines are excellent biochemical markers for bladder tumors.

Animals↗
PubMedDate not supplied

[Importance of the polyamines: review of the literature].

The polyamines, putrescine, spermidine and spermine, are low-molecular weight substances, synthesized in eucariot cells from their immediate precursor, ornithine. These nitrogen compounds are essential for growth. The organism's endogenous supply is obtained through the diet or by synthesis in the intestinal flora. The polyamines are found in fruits and vegetables, foods of animal origin (milk, eggs, fish, and meat) and fermented food products (cheese, beer, and sauerkraut). Being nitrogenated compounds, they are considered as "minor" components of the diet. Ornithine decarboxylase, a short-half life enzyme, is the key to polyamine biosynthesis. Cellular polyamines are found in free or conjugated forms, the latter made possible, above all, by the presence of positive charges in their molecules. Their particular structure facilitates interaction with anions and binding to nuclear and membrane structures, particularly phospholipids, proteins and DNA. The organism's requirements for these substances are elevated during phases of intense growth or increased demand; thus, the nutritional supply can be crucial during the evolution of processes that involve a high degree of loss combined with deficits in endogenous biosynthesis. Increased tissue and organ polyamine concentrations correlate with diseases of neoplastic origin. It has been hypothesized that polyamine inhibition could be a therapeutic mechanism for such conditions. The supply of polyamines in artificial nutrition has not been measured and there are few data on the effects of artificial nutrition on circulating levels or the usual sites of storage in the body.

Diet↗
PubMed1999

Polyamine transport in bacteria and yeast.

The polyamine content of cells is regulated by biosynthesis, degradation and transport. In Escherichia coli, the genes for three different polyamine transport systems have been cloned and characterized. Two uptake systems (putrescine-specific and spermidine-preferential) were ABC transporters, each consisting of a periplasmic substrate-binding protein, two transmembrane proteins and a membrane-associated ATPase. The crystal structures of the substrate-binding proteins (PotD and PotF) have been solved. They consist of two domains with an alternating beta-alpha-beta topology, similar to other periplasmic binding proteins. The polyamine-binding site is in a cleft between the two domains, as determined by crystallography and site-directed mutagenesis. Polyamines are mainly recognized by aspartic acid and glutamic acid residues, which interact with the NH(2)- (or NH-) groups, and by tryptophan and tyrosine residues that have hydrophobic interactions with the methylene groups of polyamines. The precursor of one of the substrate binding proteins, PotD, negatively regulates transcription of the operon for the spermidine-preferential uptake system, thus providing another level of regulation of cellular polyamines. The third transport system, catalysed by PotE, mediates both uptake and excretion of putrescine. Uptake of putrescine is dependent on membrane potential, whereas excretion involves an exchange reaction between putrescine and ornithine. In Saccharomyces cerevisiae, the gene for a polyamine transport protein (TPO1) was identified. The properties of this protein are similar to those of PotE, and TPO1 is located on the vacuolar membrane.

Amino Acid Sequence↗
PubMedDate not supplied

Duodenogastric reflux and gastric mucosal polyamines in the non-operated stomach and in the gastric remnant after Billroth II gastric resection. A role in gastric carcinogenesis?

BACKGROUND: The relationship between bile reflux and gastric cancer is not defined. In order to verify whether a relationship exists, we evaluated the duodenogastric reflux and the mucosal polyamines concentration, polycation compounds actively involved in cell proliferation, in the non-operated stomach and in gastric remnant after Billroth II gastric resection, a precancerous condition. MATERIALS AND METHODS: The study was performed on three groups of subjects: A) 43 subjects with slight dispeptic symptoms, never operated on; B) 54 cholecystectomized subjects; C) 38 subjects operated on Billroth II gastric resection for duodenal ulcer. Duodenogastric reflux was assessed by measuring the concentration of bile acids in gastric juice and expressed as Fasting Bile Reflux in micromol/hour. Gastric mucosal polyamine concentration was assessed by High Performance Liquid Chromatography and expressed in nmol/mg of proteins. RESULTS: The lowest levels of Fasting Bile Reflux (7.95 micromol/hour) and polyamines (7.09 nmol/mg proteins) were observed in subjects never operated on. The middle values were present after cholecystectomy (Fasting Bile Reflux = 18 micromol/hour; polyamines = 8.14 nmol/mg proteins). The highest values were observed after Billroth II gastric resection (Fasting Bile Reflux = 830 micromol/hour; polyamines 11.74 nmol/mg proteins) (Kruskal-Wallis test, p = 0.0001). There was a positive correlation between Fasting Bile Reflux and polyamines (Spearman's rank = 0.33; p = 0.0008). CONCLUSIONS: High levels of duodenogastric reflux observed after Billroth II gastric resection are associated with high polyamine concentration in the gastric mucosa. Bile reflux can be considered an important causal factor of the increased risk of gastric stump cancer after Billroth II gastric resection.

Adult↗
PubMed2000

Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy.

Two lines of transgenic mice were produced with constitutive expression of antizyme-1 in the heart, driven from the cardiac alpha-myosin heavy chain promoter. The use of engineered antizyme cDNA in which nucleotide 205 had been deleted eliminated the need for polyamine-mediated frameshifting, normally necessary for translation of antizyme mRNA, and thus ensured the constitutive expression of antizyme. Antizyme-1 is thought to be a major factor in regulating cellular polyamine content, acting both to inhibit ornithine decarboxylase (ODC) activity and to target it for degradation, as well as preventing polyamine uptake. The two transgenic lines had substantial, but different, levels of antizyme in the heart, as detected by Western blotting and by the ability of heart extracts to inhibit exogenous purified ODC. Despite the high levels of antizyme, endogenous ODC activity was not completely abolished, with 10-39% remaining, depending on the transgenic line. Additionally, a relatively small decrease (30-32%) in cardiac spermidine content was observed, with levels of putrescine and spermine unaffected. Interestingly, although the two lines of transgenic mice had different antizyme expression levels, they had almost identical cardiac polyamine content. When treated with a single acute dose of isoprenaline (isoproterenol), cardiac ODC activity and putrescine content were substantially increased (by 14-fold and 4.7-fold respectively) in non-transgenic littermate mice, but these increases were completely prevented in the transgenic mice from both founder lines. Prolonged exposure to isoprenaline also caused increases in cardiac ODC activity and polyamine content, as well as an increase in cardiac growth, in non-transgenic mice. Although the increases in cardiac ODC activity and polyamine content were prevented in the transgenic mice from both founder lines, the increase in cardiac growth was unaffected. These transgenic mice thus provide a valuable model system in which to study the importance of polyamine levels in cardiac growth and electrophysiology in response to stress.

Animals↗
PubMed2001

Polyamines of the hyperthermophilic archaebacteria belonging to the genera Thermococcus and Methanothermus and two new genera Caldivirga and Palaeococcus.

Cellular polyamines of eight new thermophilic archaebacteria were investigated to determine the chemotaxonomic significance of polyamine distribution profiles. Hyperthermoacidophilic Caldivirga maquilingensis belonging to the family Thermoproteaceae of the Crenarchaeota have a unique polyamine profile comprising spermidine, norspermidine and norspermine as the major polyamines. Within the order Thermococcales of the Euryarchaeota, the major polyamines of an extremely thermophilic terrestrial species of Thermococcus, T. zilligii, were spermidine and agmatine, whereas hyperthermophilic submarine species of Thermococcus and hyperthermophilic submarine Palaeococcus ferrophilus contained a quaternary branched penta-amine, N4-bis(aminopropyl)spermidine, as a major polyamine. A hyperthermophilic methanogen, Methanothermus sociabilis, belonging to Euryarchaeota, contained spermidine and spermine as the major polyamine.

Polyamines↗
PubMed2002

Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors.

The essential requirement for polyamines for normal cell growth and differentiation may be partly attributed to their influence on gene expression, a process regulated by the acetylation state of nucleosomal histones. We used transgenic mice to examine the effects of constitutive expression of ornithine decarboxylase (ODC), a key rate-limiting enzyme in polyamine biosynthesis, on histone acetylation in epithelial cells in skin. As compared with the skin of normal littermate mice, both intrinsic histone acetyltransferase (HAT) and deacetylase activities are elevated in ODC transgenic skin. Skin tumors that form spontaneously in ODC/Ras double transgenic mice exhibit exceptionally high HAT activity having a distinct specificity for Lys-12 in the tail domain of histone H4, which may have implications for gene transcription. However, acetylation of histones by HAT enzymes was impeded in cultured ODC transgenic keratinocytes, and there were only modest changes in levels of acetylated histones in the skin of ODC transgenic mice. Treatment with the ODC enzyme inhibitor alpha-difluoromethylornithine, which results in regression of ODC/Ras tumors, reverses the effects on HAT and deacetylase enzyme function, implicating polyamine biosynthesis in the regulation of histone acetylation. Polyamines do not directly stimulate the enzymatic activity of either p300 or p300/CREB-binding protein (CBP)-associated factor, members of two distinct classes of HAT enzymes, implying that the elevated CBP/p300-associated HAT activity detected in ODC transgenic skin is attributable to indirect influence of polyamines. These results suggest that multiple mechanisms exist by which endogenous polyamines influence chromatin in mammals. Furthermore, they suggest that the elevated polyamine levels inherent in many solid tumors alter chromatin structure, likely affecting gene expression and promoting the neoplastic process.

Acetylation↗
PubMed2001

In vitro effect of diamidines on intracellular polyamines of Acanthamoeba polyphaga.

Treatment with the drugs berenil, dibromopropamidine, pentamidine and CGP-4O-215 were found to alter levels of intracellular polyamines of Acanthamoeba polyphagia trophozoites in organisms. While the polyamine, spermidine, consistently remained higher in the control organisms incubated at 8, 16 and 32 h respectively, the level fluctuated significantly from below 5% to 40% in drug-treated organisms. A novel polyamine (polyamine F), yet to be identified, representing 80% of the total polyamine extracts and seen in control organisms after 48 h of incubation (stationary phase), was seen much earlier in the drug treated organisms. Pentamidine, dibromopropamidine and CGP-4O-215 induced the appearance of the novel polyamine in the trophozoites after only 8 h of incubation with the drugs while induction by berenil occurred after 32 h. It is suggested that diamidine drugs either induce encystment or alter the pathway of polyamine metabolism in Acanthamoeba. If inducing encystment is the main mode of reaction, then drugs that induce early encystment will be less effective in treatment than those that delay it.

Acanthamoeba↗
PubMed2002

Involvement of polyamines in root development at low temperature in the subantarctic cruciferous species Pringlea antiscorbutica.

Polyamine involvement in root development at low temperature was studied in seedlings of Pringlea antiscorbutica R. Br. This unique endemic cruciferous species from the subantarctic zone is subjected to strong environmental constraints and shows high polyamine contents. In the present study, free polyamine levels were modified by inhibitors of polyamine biosynthesis (D-arginine, difluoromethylornithine, cyclohexylammonium, and methylglyoxal-bis-guanylhydrazone) and variations of the endogenous pools were compared to changes in root growth. The arginine decarboxylase pathway, rather than that of ornithine decarboxylase, seemed to play a major role in polyamine synthesis in Pringlea antiscorbutica seedlings. Root, but not shoot, phenotypes were greatly affected by these treatments, which modified polyamine endogenous levels according to their expected effects. A positive correlation was found between agmatine level and growth rate of the primary root. Spermidine and spermine contents also showed positive correlations with primary root growth whereas the putrescine level showed neutral or negative effects on this trait. Free polyamines were therefore found to be differentially involved in the phenotypic plasticity of root architecture. A comparison of developmental effects and physiological concentrations suggested that agmatine and spermine in particular may play a significant role in the control of root development.

Acclimatization↗
PubMed2002

Growth status significantly affects the response of human lung cancer cells to antitumor polyamine-analogue exposure.

Human solid tumors frequently have a relatively small growth fraction,which interferes with the action of many chemotherapeutic agents that target actively cycling cells. Several polyamine analogues are currently being developed for clinical application against human solid tumors including N1,N11-bis(ethyl)norspermine. Therefore, an effort was made to examine the effects of growth rate on polyamine-analogue efficacy. Low growth fraction (LGF) cell cultures of the human non-small cell lung cancer cell line NCI-H157 were generated to partially mimic solid tumors with low mitotic indices. Log-phase cells were compared with LGF cells with respect to cell survival and biochemical effects after exposure to polyamine analogues. The results demonstrate generally that LGF NCI-H157 cells were sensitive to analogue treatment. However, the dose necessary to elicit a response in LGF cells was an order of magnitude higher than the dose needed in log-phase cells. Additionally, the biochemical effects of analogues were similar between log phase and LGF cells with regard to a down-regulation of polyamine biosynthesis as measured by ornithine decarboxylase activity and an increase in polyamine catabolism as indicated by an increase in spermidine/spermine N1-acetyltransferase activity. However, biochemical effects were less dramatic in the LGF cells than those observed in the log-phase cells. The overall results of these studies suggest that the growth status of solid tumors can significantly affect the response to antitumor polyamine analogues, and growth fraction must be considered in the continued development and use of the polyamine analogues.

Cell Division↗
PubMedDate not supplied

Suramin selectively inhibits carcinoma cell growth that is dependent on extracellular polyamines.

Polyamines are necessary for tumour cell growth. Inhibition of endogenous polyamine biosynthesis results in compensatory up-regulation of polyamine uptake. Here, the combined effect of suramin and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) on human carcinoma cell proliferation was studied. Suramin selectively inhibited the growth of tumour cells made dependent on extracellular polyamines by DFMO-treatment. In an animal tumour model, low non-toxic doses of suramin resulted in a 2-fold increase in DFMO tumour growth reduction. Moreover, suramin bound strongly to polyamine-agarose and significantly inhibited polyamine uptake in DFMO-treated cells. Our results indicate that non-toxic doses of suramin augment tumour growth inhibition by DFMO, and that a combination of these well-studied anticancer drugs may represent an additional strategy for cancer treatment.

Animals↗
PubMed2003

Drugs affecting the cell cycle via actions on the polyamine metabolic pathway.

Polyamines (putrescine, spermidine, and spermine) are ubiquitous cellular components that have multiple functions, including actions affecting the cell cycle. Polyamine biosynthesis and content is altered during the course of cell cycling via changes in two key biosynthetic enzymes, ornithine decarboxylase and S-adenosyl-methionine decarboxylase. Decreases in polyamine content and/or alterations in the relative amounts of polyamines can be achieved by treatment with inhibitors of these enzymes or by application of polyamine analogues, which subvert mechanisms for polyamine homeostasis and may interfere directly with polyamine-dependent processes. Such changes cause G1 and G2-M cell cycle blocks that can be brought about via induction of p21WAF1/CIP1.

Animals↗
PubMed2003

Polyamine levels and ornithine decarboxylase activity in blood and erythrocytes in human diseases.

Serum and erythrocyte levels of the polyamines spermine, spermidine and putrescine, as well as ornithine decarboxylase in erythrocytes, were studied in patients with different neoplasms (breast, lung and colon cancer) and in those with a nonmalignant proliferative disease (familial polyposis). The blood levels of polyamines and the spermine/putrescine ratio were significantly higher in all tumors and in nonmalignant colon polyposis. In erythrocyte ornithine decarboxylase activity, spermine and spermidine levels, as well as spermidine/putrescine and spermine/putrescine ratios showed a significant decrease after surgery and chemotherapy. Our data suggest that high levels of blood polyamines and erythrocyte ornithine decarboxylase activity are related to cell proliferation and cancer treatment, but that levels of polyamines in serum and erythrocytes are still significantly high after cancer treatment and are similar to those in polyposis disease. Polyamines are related to nuclear activity during differentiation; therefore, the altered turnover of polyamines could be a sign of abnormal nuclear function. Since polyamines stimulate protooncogene expression, their high levels could be considered an important cofactor in malignant cell transformation.

Adenocarcinoma↗
PubMed2005

[Effects of exogenous polyamines on the growth and activities of H+-ATPase and H+-PPase in cucumber seedling roots under hypoxia stress].

The effects of exogenous polyamines on the growth, polyamines contents, the activities of H(+)-ATPase and H(+)-PPase of plasma membrane and tonoplast in cucumber seedling roots under root-zone hypoxia stress were studied under hydroponic culture. The results showed that the growth of cucumber roots was significantly inhibited by hypoxia stress (Table 1). While the growth inhibition in cucumber roots by hypoxia stress could be alleviated by spraying exogenous polyamines. From these results (Table 1 and 2) we can conclude that Spd played an active physiological role in relieving hypoxia stress and Put exerted actively physiological role by enhancing Spd biosynthesis. The results also showed that the endogenous polyamine contents in cucumber roots were increased by hypoxia stress and spraying exogenous polyamines. Exogenous polyamines application obviously promoted the H(+)-ATPase activities of plasma membrane in cucumber roots (Fig.1), but did not significantly affect the H(+)-ATPase and H(+)-PPase activities of tonoplast in cucumber roots (Fig.2,3). The results suggested that exogenous polyamines could enhance hypoxia resistance of cucumber seedlings by increasing H(+)-ATPase activities of plasma membrane in cucumber roots.

Cucumis sativus↗
PubMed2006

Perturbation of polyamine metabolism and its relation to cell death in human colon cancer cells treated by 7beta-hydroxycholesterol and 7beta-hydroxysitosterol.

7beta-OHsitosterol and 7beta-OHcholesterol are natural compounds of plant and animal cells with high structural similarity. Recently it was reported that both compounds induced apoptosis on human colon cancer cells by targeting different signalling pathways. Our study aimed at comparing their effects on polyamine metabolism and its relation to apoptosis. When human colon cancer cells were exposed to 7beta-OHsitosterol and to 7beta-OHcholesterol at concentrations inhibiting growth by the same degree, both compounds caused a reduction of polyamine biosynthetic enzyme activity, of the polyamine pools, and an increase of N1-acetylspermidine concentration indicating the enhancement of polyamine catabolism. Exogenous putrescine did not prevent cell death caused by 7beta-OHsitosterol, whereas 7beta-OHcholesterol-induced apoptosis was inhibited. MDL 72527, an inhibitor of polyamine oxidase, an enzyme of the polyamine catabolic pathway, potentiated the antiproliferative effects of 7beta-OHcholesterol by increasing the N1-acetylspermidine pool and enhanced the accumulation of apoptotic cells. In contrast, MDL 72527 did not change the apoptosis rate and the N1-acetylspermidine content in cells treated with 7beta-OHsitosterol. These data indicate that polyamine metabolic perturbations triggered by 7beta-OHcholesterol but not by 7beta-OHsitosterol are related to cell death.

Biogenic Polyamines↗
PubMed1991

[Inhibitory effects of interferon and inhibitors of polyamine biosynthesis on clonal growth of Raji cells derived from Burkitt's lymphoma].

Interferon (IFN)-alpha, -gamma, and two inhibitors of polyamine biosynthesis (alpha-difluoromethyl ornithine; DFMO and methyl glyoxal bis-guanyl hydrazone; MGBG) inhibited the clonal growth of Raji cells. The combination-treatment using two agents, particularly IFN-alpha and DFMO represented synergistic effects. In order to investigate the mechanism of the synergism between IFNs and inhibitors of polyamine biosynthesis, the concentrations of polyamines and the levels of 2'-5' oligo-adenylate synthetase (2-5 AS) activity in the treated Raji cells were determined. Not only the inhibitors of polyamine biosynthesis, but also IFNs decreased the content of spermidine in the cells. Furthermore, the clonogenic growth-inhibition by IFN-alpha was recovered partially by exogenous spermidine. On the other hand, 2-5AS activity in the cells was elevated to 57 times by the treatment with interferon-alpha and further more, the combinations of IFN and the inhibitors of polyamine biosynthesis induced higher activities of 2-5AS as compared with those by each agent. From these results, it was suggested that the synergistic effects of IFNs in combinations with inhibitors of polyamine biosynthesis on the inhibition of clonal growth of Raji cells were closely associated with the decrease of intracellular polyamine level and the increase of 2-5AS activity in the treated cells.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Effect of polyamine deprivation on the survival of intracranial glioblastoma bearing rats.

It has previously been shown that systematic polyamine deprivation results in the almost complete inhibition of the growth of several solid tumors. The same polyamine deficient diet (containing antibiotics for the decontamination of the gastrointestinal tract, the ornithine decarboxylase inhibitor 2-(difluoromethyl)ornithine, and the polyamine oxidase inhibitor N1, N4-bis-(2,3-butadienyl)putrescine; "drug-containing polyamine deficient chow", DC-PDC) was applied for the first time to the treatment of rats with an intracranial tumor. Rats received intracortical grafts of C6 rat glioblastoma cells, and the length of their survival was determined. Treatment with DC-PDC, starting four days after tumor cell inoculation, significantly prolonged the median survival of the glioblastoma-bearing rats. The results underline the general growth inhibitory effect of systematic polyamine deprivation. Since the effect of polyamine restriction on tumor growth is reversible, combinations with cytotoxic drugs have to be found which exploit the changed functions of polyamine deficient tumor cells.

Animals↗