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PubMed1989

Premalignant alterations in rat colonic N1-acetylspermidine levels induced by 1,2-dimethylhydrazine: effects of a high corn oil dietary regimen.

Recently, our laboratory has demonstrated that elevations in the levels of N1-acetylspermidine could be detected in the colonic mucosa of rats after administration of 1,2-dimethylhydrazine for 15 weeks, i.e., before the development of colon tumors. Since prior studies have indicated that diets high in fat, particularly unsaturated fat, promote the development of dimethylhydrazine-induced tumors, it was of interest to examine the effect of a corn oil dietary regimen (20% by weight) on colonic N1-acetylspermidine levels in this model of colonic adenocarcinoma. Four groups of rats were used in these studies: chow, chow + carcinogen, corn oil and corn oil + carcinogen. The carcinogen groups received weekly s.c. injections of 1,2-dimethylhydrazine (20 mg/kg body wt) for 15 weeks, while the control groups received diluent. 1 week after the last injection, animals from each group were killed, and their proximal and distal colons were resected, examined and compared with respect to polyamine levels, including N1-acetylspermidine, as well as the activities of ornithine decarboxylase, spermidine N1-acetyltransferase, and polyamine oxidase. In view of previous studies which suggested that N1-acetylspermidine levels may be elevated in the urine of patients with various malignancies, it was also of interest to examine and compare the urinary levels of this acetylated polyamine in animals from each group. The results of these experiments demonstrated that: (1) the levels of N1-acetylspermidine in the distal colonic segment were found to be increased approx. 25 and 80% in the chow + carcinogen and corn oil + carcinogen groups, respectively, compared to their control counterparts; (2) the activities of spermidine N1-acetyltransferase in the distal colonic segments of chow + carcinogen and corn oil + carcinogen animals were increased 1.5- and 2-fold, respectively, compared to control values; (3) dimethylhydrazine administration did not affect the levels of this acetylated polyamine or spermidine N1-acetyltransferase activities in the proximal colon, but, in general, did increase the levels of putrescine and spermidine as well as ornithine decarboxylase activities in both colonic segments of animals fed chow or corn oil diets; and (4) elevated urinary levels of N1-acetylspermidine did not appear to be a reliable 'premalignant' marker in this experimental model of colonic adenocarcinoma.

1,2-Dimethylhydrazine↗
PubMed2005

Polyamines inhibit both platelet aggregation and glycoprotein IIb/IIIa activation.

Platelet aggregation is inhibited by the polyamines putrescine, spermidine, and spermine. To date, the mechanism of action has not been clearly identified. Evidence suggests that polyamines may interact with the fibrinogen receptor (GP IIb/IIIa), interfering with platelet-platelet attachment. The effect of polyamines on human platelet aggregation and GP IIb/IIIa activation was evaluated. For the aggregation experiments, platelets were obtained from heparin- or citrate-collected blood. Our results indicate that the polyamines putrescine, spermidine, and spermine cause a dose-dependent inhibition of ADP- or collagen-mediated platelet aggregation with an order of potency spermine>spermidine>putrescine. In addition, spermine arrests or inhibits thrombin-, epinephrine-, arachidonate-, or ristocetin-induced platelet aggregation. Expression of platelet membrane glycoproteins IIb, IIIa, and IX is not reduced by polyamines. However, spermine inhibits the ADP- or thrombin-induced activation of GP IIb/IIIa. It is concluded that the final step in aggregation, common to all agonists, ie, fibrinogen binding to GP IIb/IIIa, is inhibited by spermine through inhibition of the agonist-induced activation of GP IIb/IIIa that precedes fibrinogen-ligand binding.

Biogenic Polyamines↗
PubMed2003

Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.

Molecular, biochemical and genetic characterization of ornithine decarboxylase, S -adenosylmethionine decarboxylase and spermidine synthase establishes that these polyamine-biosynthetic enzymes are essential for growth and survival of the agents that cause African sleeping sickness, Chagas' disease, leishmaniasis and malaria. These enzymes exhibit features that differ significantly between the parasites and the human host. Therefore it is conceivable that exploitation of such differences can lead to the design of new inhibitors that will selectively kill the parasites while exerting minimal, or at least tolerable, effects on the parasite-infected patient.

Animals↗
PubMed1990

Role of polyamines in the early adaptive response to jejunectomy in the rat: effect of DFMO on the ileal villus:crypt axis.

To study the role of the polyamines putrescine, spermidine and spermine and of the enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO) along the villus:crypt axis at the crucial early stage of the ileal adaptive response to jejunectomy, we measured polyamine concentrations and the activities of ODC, DAO and alkaline phosphatase (a marker of enterocyte maturity) in epithelial cells isolated by the Weiser technique from villus tips, mid villi, lower villi and crypts 4 days after surgery in transected control (TRC) and jejunectomised rats untreated or given the specific ODC blocker, alpha-difluoromethyl ornithine (DFMO, 2% in drinking water beginning 3 days before surgery). In the TRCs, there was a diminishing villus tip-to-crypt gradient not only in alkaline phosphatase but also in ODC and DAO activities. After jejunectomy, there were up to 93% increases in mean enterocyte ODC activity when compared with the corresponding cell fractions from the TRCs, but in both the control and jejunectomised rats, DFMO treatment markedly inhibited ODC activity (p less than 0.05-0.01) and reduced spermidine and particularly putrescine concentrations (p less than 0.005-0.001) in all four cell fractions. Only 4 days post-operation, jejunectomy stimulated a significant increase in ileal wet weight but DFMO treatment completely prevented this adaptive response and significantly reduced segmental intestinal weight (mg/cm) in the TRCs. These results (i) extend our knowledge of polyamines and related enzymes along the villus:crypt gradient in the normal intestine, (ii) provides the first data on these variables after resection, and (iii) lend further support to the hypothesis that changes in enterocyte ODC activity and in putrescine and spermidine concentrations play an important role in initiating the ileal adaptive response to proximal small bowel resection in the rat.

Adaptation, Physiological↗
PubMed1990

[Detection of polyamines by a new enzymatic differential assay. (7) Fundamental study on a new enzymatic differential assay of tissue polyamines].

The enzymatic method for isolation and determination of urinary polyamines was modified to measure the polyamines in tissue. High recovery rates of polyamines in tissue by the enzymatic method were obtained, namely, 104.5 +/- 7.4% for diamine, 104.7 +/- 23.3% for spermidine and 104.8 +/- 7.5% for spermine. The results obtained by this method correlated well with those obtained by high performance liquid chromatography, and a close correlation was demonstrated for all fractions: diamine r = 0.8991, y = 0.9916x + 0.0499; spermidine r = 0.8936, y = 1.2073x + 0.1005; spermine r = 0.8921, y = 1.2200x-0.2194, (n = 13).

Biogenic Polyamines↗
PubMedDate not supplied

Effect of tamoxifen on 1,2-dimethylhydrazine-HCl-induced colon carcinogenesis in rats.

BACKGROUND: Evidence suggests that steroid hormones may affect the natural history of colon cancer. METHODS: Baseline levels of estrogen receptors, polyamines, and ornithine decarboxylase in colonic mucosa, and blood estradiol were measured in 10 normal Sprague-Dawley outbread female rats. Therefore, 151 rats were fed a 15% fat diet and divided into three groups. Rats in the control group (n = 20) received weekly s.c injections of the 1,2-Dimethylhydrazine-HCl (DMH) vehicle. To induce colon cancer, 131 rats received weekly subcutaneous injections of DMH (20 mg/kg). Of these 131 rats, 65 also ingested 0.5 microgram/g tamoxifen, daily. Half of the rats in each group were sacrificed at 14 weeks, the remainder at 28 weeks. All measurements were repeated at these times and tumor incidence was calculated. RESULTS: The number of rats with tumors was 41% higher (P = .07) in rats treated with DMH vs those treated with tamoxifen and DMH (72.7% vs 51.5%). Tumor cells in both groups had higher levels of polyamines and ornithine decarboxylase activities (P = .03 to P < .001) and lower levels of estrogen receptors (P = .005) to P < .001) compared to adjacent normal colonic mucosa. Estrogen receptors were not detected in the colons of the rats in the control group. No correlations were found between estradiol and estrogen receptors in normal (r = .01, P = .95) or tumor (r = .03, P = .86) cells, or between polyamines or ornithine decarboxylase and estrogen receptors in normal (r = .01 to .14, P = .63 to .95) or tumor (r = .07 to .26, P = .16 to .86) cells. CONCLUSIONS: Tamoxifen reduced the incidence of DMH-induced colon cancer in rats and may thus have chemopreventive effects. Although it was not statistically significant, further studies are justified to continue this line of research.

1,2-Dimethylhydrazine↗
PubMed1990

Molecular genetics of polyamine synthesis in eukaryotic cells.

The polyamines putrescine, spermidine and spermine are important cellular constituents involved in the regulation of cell growth and differentiation. Their intracellular levels are regulated by a multitude of mechanisms affecting their synthesis, degradation, uptake and excretion. As a result of the application of molecular biology techniques, some of these mechanisms are presently being unravelled, and are providing a basis for the rational development of novel agents effective against proliferative disorders and various parasitic diseases.

Adenosylmethionine Decarboxylase↗
PubMed2003

Visually driven regulation of intrinsic neuronal excitability improves stimulus detection in vivo.

Neurons adapt their electrophysiological properties to maintain stable levels of electrical excitability when faced with a constantly changing environment. We find that exposing freely swimming Xenopus tadpoles to 4-5 hr of persistent visual stimulation increases the intrinsic excitability of optic tectal neurons. This increase is correlated with enhanced voltage-gated Na+ currents. The same visual stimulation protocol also induces a polyamine synthesis-dependent reduction in Ca2+-permeable AMPAR-mediated synaptic drive, suggesting that the increased excitability may compensate for this reduction. Accordingly, the change in excitability was prevented by blocking polyamine synthesis during visual stimulation and was rescued when Ca2+-permeable AMPAR-mediated transmission was selectively reduced. The changes in excitability also rendered tectal cells more responsive to synaptic burst stimuli, improving visual stimulus detection. The synaptic and intrinsic adaptations function together to keep tectal neurons within a constant operating range, while making the intact visual system less responsive to background activity yet more sensitive to burst stimuli.

Animals↗
PubMedDate not supplied

[Levels of extracellular DNA and polyamines as criteria of resistance to chemotherapy in patients with acute leukemia].

Content of polyamines and extracellular DNA were studied in blood of patients with acute leukoses which did not respond to chemotherapy. Concentration of total polyamines was distinctly lower in blood of patients with acute lymphoblast and myeloblast leukoses as compared with healthy persons. Free and total polyamines were unaltered in blood of these patients after cytostatic therapy. In the patients with acute leukoses content of extracellular DNA was 2-fold higher as compared with controls. The high DNA content was maintained during the therapeutic course. Absence of any alterations in the biochemical patterns studied suggest that the patients with acute leukoses did not respond to the course of treatment used.

Adolescent↗
PubMed1991

Polyamine biosynthesis in arginine-starved and refed rats.

Growth of rats fed with a synthetic diet was studied under control conditions (arginine-rich), arginine starvation, and arginine starvation/refeeding. Hepatic polyamine concentrations and ornithine decarboxylase (ODC-)activity were determined for each population. In the livers of arginine-starved rats putrescine was decreased to half the control content within 8 days; upon refeeding, it returned to control levels within another 8 days. Spermidine content in liver tissue of arginine-starved rats remained rather stable for 7 days, but thereafter dropped to half the original value within two days. Refeeding for a period of 11 days was not enough to restore the spermidine content. The effects of arginine starvation/refeeding on spermine were very similar to those of spermidine. ODC specific activity, when correlated with growth, was higher in livers of arginine-starved rats than in control animals. Refeeding caused a decrease in ODC-activity although growth arrest was completely released. This apparent uncoupling of growth and ODC stimulation supports the theory that ODC in rat liver is regulated at three levels: first the growth-related component which is observed after stimulation by growth-hormone; second the known feed back control by polyamines, e.g. via antizyme; third the regulation at the level of the substrate supply which has been shown in this work. This is not a unique finding since very similar results have been obtained in previous experiments with the protozoan Tetrahymena thermophila. A remarkable observation of these assays was that L-ornithine, when added to the arginine-free diet was not able to substitute for L-arginine in directing growth and growth related processes.

Animals↗
PubMed2001

Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells.

N(1),N(11)-Diethylnorspermine (DENSPM) is a polyamine analogue with clinicalrelevance as an experimental anticancer agent and the ability to elicit a profound apoptotic response in certain cell types. Here, we characterize the polyamine effects and apoptotic signaling events initiated by treatment of SK-MEL-28 human melanoma with 10 microM DENSPM. Maximal induction of the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) and polyamine pool depletion were seen by 16 h, whereas early apoptosis was first apparent at 36 h. Intermediate events related to apoptotic signaling were sought between 16 and 36 h. A loss of mitochondrial transmembrane potential (Deltapsi(m)) beginning at 24 h was followed by the release of cytochrome c into the cytosol at 30 h. Loss of mitochondrial integrity was accompanied by caspase-3 activation and poly(ADP-ribose) polymerase digestion from 30 to 36 h. The caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone rendered cells resistant to analogue-induced caspase-3 activation and reduced the apoptotic response in a dose-dependent manner. Because polyamine reduction achieved by inhibitors of polyamine biosynthesis inhibited growth but did not cause apoptosis, we looked for alternative polyamine-related events, focusing on induction of SSAT. Three DENSPM analogues that differentially induced SSAT activity but similarly depleted polyamine pools revealed a close correlation between enzyme induction and cytochrome c release, caspase activation, and apoptosis. Dose-dependent inhibition of polyamine oxidase, an enzyme that oxidizes acetylated polyamines generated by SSAT and releases toxic by-products such as H(2)O(2) and aldehydes, prevented cytochrome c release, caspase activation, and apoptosis. Taken together, the findings indicate that DENSPM-induced apoptosis is at least partially initiated via massive induction of SSAT and related oxidative events and subsequently mediated by the mitochondrial apoptotic signaling pathway as indicated by cytochrome c release and caspase activation.

Acetyltransferases↗
PubMed2004

Maintained regulation of polyamines in spinal cord from patients with amyotrophic lateral sclerosis.

Levels of the polyamines putrescine, spermidine, and spermine were investigated in postmortem spinal cord from seven patients with amyotrophic lateral sclerosis (ALS) and seven control subjects. The method consisted of precolumn derivatization of the polyamines, followed by high-performance liquid chromatography (HPLC) analysis and fluorescence detection. The stability of the polyamines was examined in rat spinal cord during the interval of 0-36 h postmortem. The levels of putrescine, spermidine, and spermine increased by 32%, 15%, and 2%, respectively. Polyamine levels did not differ significantly between the ALS group and the control group, suggesting a maintained regulation of polyamines in the end stage of the disease. However, an effect of gender on the levels of spermidine and spermine was observed. Levels of spermidine and spermine in the ventral horn region of female ALS patients were significantly higher in comparison with the same region of the male ALS group (p<0.05). The female ALS group also presented significantly higher levels of spermidine in comparison with female controls (p<0.05).

Aged↗
PubMed1998

Polyamine modulation of mitochondrial calcium transport. I. Stimulatory and inhibitory effects of aliphatic polyamines, aminoglucosides and other polyamine analogues on mitochondrial calcium uptake.

In this study, the regulation of mitochondrial Ca2+ transport by polyamines structurally related to spermine and by analogous polycationic compounds was characterized. Similar to spermine, a number of amino groups containing cationic compounds exerted a dual effect on Ca2+ transport of isolated rat liver mitochondria: a decrease in Ca2+ uptake velocity and an enhancement of Ca2+ accumulation. In contrast to the effects of spermine and other aliphatic polyamines, however, the accumulation-enhancing effect of aminoglucosides, basic polypeptides, and metal-amine complexes turned into an inhibition of Ca2+ accumulation at higher concentrations. Within groups of structurally related compounds, the potency to decrease Ca2+ uptake velocity and to enhance Ca2+ accumulation correlated with the number of cationic charges. The presence of multiple, distributed cationic charges was a necessary, but not sufficient criterion for effects on mitochondrial Ca2+ transport, because cationic polyamines and basic oligopeptides which did not enhance mitochondrial Ca2+ accumulation could be identified. Spermine was not able to antagonize the blocking of Ca2+ uptake by ruthenium red, but rather showed an apparent synergism, which can be explained as a displacement of membrane-bound Ca2+ by spermine. The aminoglucosides, gentamicin and neomycin, but not the inactive polyamine bis(hexamethylene)-triamine, inhibited the binding of spermine to intact mitochondria. Apparently, the binding of spermine, gentamicin, and a number of polyamine analogues to low-affinity binding sites at mitochondria, which have low, but distinct structural requirements and which may correspond to phospholipid headgroups, indirectly influences the activity state of the mitochondrial Ca2+ uniporter. The ability of aminoglucosides to displace spermine from the mitochondria and to inhibit mitochondrial Ca2+ accumulation may contribute to the mitochondrial lesions, which are known to occur early in the course of aminoglucoside-induced nephrotoxicity.

Aminoglycosides↗
PubMed1995

Inhibition of 4-nitroquinoline-1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide, KYN-54, during the initiation and post-initiation phases.

The modifying effect of dietary exposure of a newly synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54) during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) was investigated in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with KYN-54 alone and those in a control group were given 4-NQO (20 p.p.m.) in the drinking water for 8 weeks to induce oral neoplasms. Seven days after stopping 4-NQO exposure, groups of animals fed the diets containing 100 and 200 p.p.m. KYN-54 for 10 weeks starting 1 week before 4-NQO exposure were switched to the basal diet and kept on this diet until the end of the experiment. Starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets containing 100 or 200 p.p.m. KYN-54 and maintained on these diets for 22 weeks. The other group consisted of rats given 200 p.p.m. KYN-54 alone or untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine (BrdU)-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein (AgNORs) were compared among the groups. Feeding of KYN-54 during either initiation or post-initiation phase caused a significant reduction in the frequency of tongue carcinoma (48-71% reduction, P < 0.05) and such chemopreventive efficacy was dose-related. The incidences of preneoplastic lesion in rats fed the diets mixed with KYN-54 at both doses were also decreased (P < 0.05). Dietary administration of KYN-54 also significantly decreased the labeling index of BrdUrd and the number of AgNORs per cell nucleus of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats given 4-NQO and test compound when compared to those given 4-NQO alone, but no significant difference was obtained. These results indicate that the novel synthesized retinoidal butenolide KYN-54 inhibits oral carcinogenesis initiated with 4-NQO and such inhibition may be related to suppression of cell proliferation.

4-Butyrolactone↗
PubMed2004

Spermine acts as a negative regulator of macrophage differentiation in human myeloid leukemia cells.

The role of putrescine, spermidine and spermine in phorbol 12-myristate-13-acetate (PMA)-induced macrophage differentiation was examined in human HL-60 and U-937 myeloid leukemia cells. Unlike other polyamines, spermine affected this differentiation by acting as a negative regulator. This negative regulation was established by showing that the PMA-induced macrophage phenotype, but not PMA-associated replication arrest, was abrogated (a) by replenishing the PMA-evoked decrease in cellular spermine levels with this polyamine from an exogenous source and (b) by blocking PMA-induced expression of the polyamine catabolic enzyme N(1)-spermidine/spermine acetyltransferase (SSAT) with antisense oligonucleotides in the presence of low substrate level. The PMA-evoked reduction in cellular spermine appears to result from an increase in the activity of SSAT and a decrease in the activity of ornithine decarboxylase, the polyamine biosynthetic enzyme. To a degree, these changes are due to corresponding changes in the expression of the genes that code for these enzymes. When cell differentiation is initiated, SSAT expression is increased after PMA-evoked activation of protein kinase C-beta. The present studies raise the possibility that agents able to reduce spermine levels in patients' myeloid leukemia cells may enhance the activity of differentiation therapy drugs for this type of leukemia.

Acetyltransferases↗
PubMed1996

Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin.

The modifying effects of dietary exposure of three flavonoids, chalcone, 2-hydroxychalcone, and quercetin, during the initiation and postinitiation phases of oral tumorigenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with test chemicals alone and the untreated control group were given 4-NQO [20 parts/million (ppm)] in the drinking water for 8 weeks to induce oral neoplasms. For chemopreventive study by feeding of test compounds during the initiation phase, groups of animals were given diets containing 500 ppm chalcone, 500 ppm 2-hydroxychalcone, or 500 ppm quercetin for 10 weeks, starting 1 week before 4-NQO exposure. Seven days after stopping 4-NQO exposure, these groups were switched to the basal diet and kept on this diet until the end of the experiment. For chemopreventive study by treatment with test chemicals during the postinitiation phase, starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets mixed with test chemicals and maintained on these diets for 22 weeks. The other groups consisted of rats fed diets containing 500 ppm test chemicals alone or of untreated rats. Thirty-two weeks after the start of the study, the incidence of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue epithelium, and cell proliferation activity estimated by bromodeoxyuridine labeling index were compared among the different dietary groups. Feeding of all test chemicals during either initiation or postinitiation phases caused a significant reduction in the frequency of tongue carcinoma (68-88% reduction; P < 0.05). Dietary administration of these test chemicals also significantly decreased the bromodeoxyuridine labeling index of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats treated with 4-NQO and test chemicals when compared to those given 4-NQO alone. These results indicate that the flavonoids chalcone, 2-hydroxychalcone, and quercetin present in our daily foods have an inhibitory effect on oral carcinogenesis initiated with 4-NQO, and such a modifying effect may be related partly to the suppression of cell proliferation.

4-Nitroquinoline-1-oxide↗
PubMed2000

Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

Animals↗
PubMed2002

Interaction between polyamines and bacterial outer membranes as investigated with ion-selective electrodes.

We analyzed the interaction between polyamines and the outer membrane of Escherichia coli cells using potentiometric measurements with Ca(2+), tetraphenylphosphonium (TPP(+)), and K(+) electrodes. The Ca(2+) electrode was used to examine the ability of the polyamines to release Ca(2+) from the outer membrane. The TPP(+) electrode was used to examine the ability to permeabilize the outer membrane, since the uptake of TPP(+) was enhanced when the permeability barrier of the outer membrane was disrupted. The K(+) electrode was used to examine permeabilization in the cytoplasmic membrane by monitoring the efflux of K(+) in cytosol. Although Ca(2+) release was remarkably enhanced by increasing the number of amino groups in polyamines, no TPP(+) uptake was observed with polyamines of a simple structure, such as ethylenediamine, spermidine, and spermine. TPP(+) uptake was observed when appropriate lipophilic moieties were further attached to the polyamines with three or four amino groups, indicating that the existence of bulky moieties as well as the number of amino groups is important to induce outer membrane permeabilization. Thus, 1-naphthylacetylspermine and N,N'-bis[6-[[(2-methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine (methoctramine) were especially effective in increasing the permeability of the outer membrane of E. coli cells, being comparable to polymyxin B nonapeptide, a well-known cationic peptide showing such action.

Anti-Bacterial Agents↗