In experiments, carried out with the use of a radioactive label (45Ca2+) on suspension of rat uterus myocytes treated with digitonin solution (0.1 mg/ml), influence of spermine on the Mg2+, ATP-dependent Ca2+ transport in the mitochondria was investigated. Ca2+ accumulation in the mitochondria was tested as such which was blocked by ruthenium red (10 microM) and was not sensitive to thapsigargin (100 nM). It was shown, that dependence of initial speed of Ca ions accumulation in the mitochondria on spermine concentration (0.1-10 mm) is described by a bell-shaped curve. Spermine concentration being increased in the range of 0.1-1 mM the stimulation of Ca2+ accumulation was observed, at the further increase in polyamine concentration up to 10 mM the suppression of this process took place. On the basis of the analysis of the authors experimental results and the literature data the model of complex spermine action on Ca2+ accumulation in mitochondria was proposed and analyzed. The existence of two spermine

To investigate the role of urine spermine and Spermine Risk Score in prediction of high-grade prostate cancer (HGPCa, ISUP grade group ≥2). Nine hundred and five consecutive men with elevated PSA were prospectively recruited from two hospitals. Core analyses focused on consecutive men with PSA 4-20 ng/mL (n = 600). Pre-biopsy urine without prior prostatic massage was analyzed for spermine level with ultra-high performance liquid chromatography with triple quadrupole mass spectrometer (UPLC-MS/MS). The proportions of PCa and HGPCa were compared across different spermine ranges. Logistic regressions were used to form different models, and their performances were compared using area under curve (AUC) and decision curve analysis (DCA). PCa and HGPCa were diagnosed in 30.8% (185/600) and 17.2% (103/600) men, respectively, and were significantly associated with lower urine spermine levels. Between the lowest and highest quartiles of spermine results, a threefold increase in PCa risk (49.3% vs. 16.7%) and 3

Polyamine block of inwardly rectifying potassium (Kir) channels underlies their key functional property of preferential conduction of inward K+ currents (Ficker et al., 1994; Lopatin et al., 1994, 1995; Fakler et al., 1995). As a rapid and voltage-dependent process, polyamine-mediated inward rectification provides a mechanism for moment-to-moment regulation of K+ currents in excitable tissues, shaping both the action potential and resting membrane potential in tissues such as myocardium (Bianchi et al., 1996; Lopatin et al., 2000; Priori et al., 2005; Schulze-Bahr, 2005). Akin to the ongoing challenges to understanding voltage-dependent gating of the Kv channel family, development of a molecular description of steeply voltage-dependent polyamine block is an important issue for understanding the fundamental basis of strongly rectifying Kir channel activity.. Appropriate kinetic models describe polyamine block as a multistep process, incorporating sequentially linked shallow and deep binding ...

The polyamine spermine is transported into the matrix of various types of mitochondria by a specific uniporter system identified as a protein channel. This mechanism is regulated by the membrane potential; other regulatory effectors are unknown. This study analyzes the transport of spermine in the presence of peroxides in both isolated rat liver and brain mitochondria, in order to evaluate the involvement of the redox state in this mechanism, and to compare its effect in both types of mitochondria. In liver mitochondria peroxides are able to inhibit spermine transport. This effect is indicative of redox regulation by the transporter, probably due to the presence of critical thiol groups along the transport pathway, or in close association with it, with different accessibility for the peroxides and performing different functions. In brain mitochondria, peroxides have several effects, supporting the hypothesis of a different regulation of spermine transport. The fact that peroxovanadate can inhibit

Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCG CGCGGC )2 and d (ATATATATAT) 2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. Ford (ATATATA AT) 2 it was concluded that spermine remains in a cross-major groove binding site. Conversely, for d(GCGCGCGCGC) 2 spermine reorientation via specific ligand-base-pair hydrogen-bond formation allows complexation along the major groove. The solvent plays an important role in differentiating the two binding modes. A mechanism of spermine complexation to natural DNA is postulated from these results. Past experimental data are also considered in the context of the new model. ...

TY - JOUR. T1 - Inactivation of IkB contributes to transcriptional activation of spermidine/spermine N(1)-acetyltransferase. AU - Choi, W.. AU - Proctor, L.. AU - Xia, Q.. AU - Feng, Y.. AU - Gerner, E. W.. AU - Chiao, P. J.. AU - Hamilton, S. R.. AU - Zhang, W.. N1 - Contribution: organisation=sgn,FACT1=1. PY - 2006. Y1 - 2006. U2 - 10.1002/mc.20239. DO - 10.1002/mc.20239. M3 - Article. VL - 45. SP - 685. EP - 693. JO - Molecular Carcinogenesis. JF - Molecular Carcinogenesis. SN - 0899-1987. IS - 9. ER - ...

TY - JOUR. T1 - Polyamine oxidase5 regulates arabidopsis growth through thermospermine oxidase activity. AU - Kim, Dong Wook. AU - Watanabe, Kanako. AU - Murayama, Chihiro. AU - Izawa, Sho. AU - Niitsu, Masaru. AU - Michael, Anthony J.. AU - Berberich, Thomas. AU - Kusano, Tomonobu. PY - 2014/8. Y1 - 2014/8. N2 - The major plant polyamines (PAs) are the tetraamines spermine (Spm) and thermospermine (T-Spm), the triamine spermidine, and the diamine putrescine. PA homeostasis is governed by the balance between biosynthesis and catabolism; the latter is catalyzed by polyamine oxidase (PAO). Arabidopsis (Arabidopsis thaliana) has five PAO genes, AtPAO1 to AtPAO5, and all encoded proteins have been biochemically characterized. All AtPAO enzymes function in the back-conversion of tetraamine to triamine and/or triamine to diamine, albeit with different PA specificities. Here, we demonstrate that AtPAO5 loss-of-function mutants (pao5) contain 2-fold higher T-Spm levels and exhibit delayed transition ...

p,The flavoprotein oxidase Fms1 from Saccharomyces cerevisiae catalyzes the oxidation of spermine and N(1)-acetylspermine to spermidine and 3-aminopropanal or N-acetyl-3-aminopropanal. Within the active site of Fms1, His67 is positioned to form hydrogen bonds with the polyamine substrate. This residue is also conserved in other polyamine oxidases. The catalytic properties of H67Q, H67N, and H67A Fms1 have been characterized to evaluate the role of this residue in catalysis. With both spermine and N(1)-acetylspermine as the amine substrate, the value of the first-order rate constant for flavin reduction decreases 2-3 orders of magnitude, with the H67Q mutation having the smallest effect and H67N the largest. The k(cat)/K(O2) value changes very little upon mutation with N(1)-acetylspermine as the amine substrate and decreases only an order of magnitude with spermine. The k(cat)/K(M)-pH profiles with N(1)-acetylspermine are bell-shaped for all the mutants; the similarity to the profile of the ...

My laboratory is focused on gastrointestinal mucosal inflammation and carcinogenesis. We study the host immune response to the gastric pathogen Helicobacter pylori that causes peptic ulcer disease and gastric cancer. This includes the innate immune response in macrophages and the identification of ways that this response is ineffective. We have also elucidated mechanisms whereby epithelial responses are inappropriate, leading to risk for cancer development. We study novel mechanisms for inflammation and cellular/DNA damage, which leads to increased cancer risk.We have reported that H. pylori induces the enzyme spermine oxidase (SMOX), originally known as polyamine oxidase 1, which utilizes the polyamine spermine as substrate. Generation of H2O2 by SMOX results in mitochondrial membrane depolarization, cytochrome c release, and apoptosis. Spermine itself contributes to the inadequacy of the host response, by blocking translation of inducible nitric oxide (NO) synthase (iNOS; NOS2) and hence NO production

SUMMARY: Spermine was found to inhibit the growth of various micro-organisms. The most susceptible were Staphylococcus aureus and Staph. albus, Neisseria gonorrhoeae and N. meningitidis, and to a lesser degree Bacillus anthracis. The Enterobacteriaceae were relatively resistant. The action of spermine was enhanced by an increase in pH of the medium. The antibacterial effect was bactericidal; it was slowed but not prevented by a decrease in temperature from 37 to 6°. The nutrients of various media influenced the action of spermine.

The first synthesis of the new C-branched spermine derivative 17, as well as its ability to stabilise DNA duplexes and triplexes, are reported. The C-branched spermine block 17 was converted into the corresponding O-(2-cyanoethyl)-(N,N-diisopropyl)phospho. ...

The endogenous polyamine spermine has multiple effects on the N-methyl-D-aspartate (NMDA) receptor. These include an increase in the magnitude of NMDA-induced whole-cell currents that is seen in the presence of saturating concentrations of glycine (glycine-independent stimulation), an increase in the affinity of the receptor for glycine (glycine-dependent stimulation), and voltage-dependent inhibition. Although many of the properties of native NMDA receptors are seen with homomeric NR1 receptors expressed in Xenopus oocytes, we have found that the effects of spermine are differentially regulated by NR2 subunits in heteromeric NR1/NR2 receptors. Glycine-independent stimulation by spermine occurred at homomeric NR1A receptors, which lack the amino-terminal insert in NR1, and at heteromeric NR1A/NR2B receptors but not at heteromeric NR1A/NR2A or NR1A/NR2C receptors. Glycine-independent stimulation was not seen at homomeric NR1B receptors, which include the amino-terminal insert in NR1, or at ...

The first electrophysiological studies of KcsA were performed using planar lipid bilayers, and it was quickly recognized that channels could conceivably insert in either orientation (Cuello et al., 1998; Heginbotham et al., 1999; LeMasurier et al., 2001). These studies demonstrated that KcsA is oriented predominantly in one direction in a reconstituted lipid bilayer, which corresponds to the C terminus of the channel facing the bath in an excised patch (Chakrapani et al., 2007a). Several observations from the present study suggest that KirBac1.1 reconstituted in giant liposomes has a similar preference for this orientation. First, Ba2+ and spermine block consistently show a single component, leaving ∼10% residual current, some of which could be accounted for by leak (Fig. 4). If channel orientation were 50:50, one would expect to see half the current blocked with one affinity and half with another because the binding sites for intracellular and extracellular spermine are predicted to be ...

Antizyme is induced by spermine treatment in spermine-sensitive AT2.1 cells but not in spermine-resistant AT3.1 cells.. A new model for the regulation of prostate cancer cell growth in prostate and bone.. Our work supports the following theory of prostate cancer growth regulation:. A normal function of the prostate is to produce high concentrations of spermine. Initially, most prostate cancer cells have their growth arrested or retarded by the locally high levels of spermine. The mechanism of inhibition involves the induction of antizyme by spermine. This growth arrest causes the early prostate tumors to grow very slowly, often taking decades to reach the diameter of a pea.. At some point, however, some of the tumor cells may become resistant to spermine, unable to produce antizyme in response to the local spermine. These cells will be released from growth inhibition and be able to grow more rapidly in the prostate. Tumors comprised of these resistant cells will grow faster and be more likely to ...

Catalysis of the transfer of spermine from one side of the membrane to the other. Spermine is a polybasic amine found in human sperm, in ribosomes and in some viruses, which is involved in nucleic acid packaging. Synthesis is regulated by ornithine decarb…

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

Polyamine transport actions have already been described in diverse multicellular systems, but their bioenergetic systems and molecular identification stay unclear. methylglyoxal bis(guanylhydrazone), NMDG, S2 (Schneider range 2) cells, the initial such activity referred to within a model hereditary system, and weve characterized its kinetics, ionic requirements and pharmacological profile. This activity displays particular affinity for spermine and spermidine, however, not putrescine, would depend on H+, however, not Na+, and displays a pharmacological profile strikingly identical to that from the Slc22 (solute carrier 22) category of solute companies. These data will facilitate additional tests for the molecular id and characterization from the spermine/spermidine transporter in as well as perhaps in various other species aswell. MATERIALS AND Strategies Reagents [14C]Spermine tetrahydrochloride (113?Ci/mol) and [14C]spermdine trihydrochoride (112?Ci/mol) had been extracted from Amersham ...

Experimental. 1H-NMR determinations. tRNAPhe from brewers yeast was from Sigma. It was dissolved in 0.5 mL of a buffer containing 50 mM sodium cacodylate, 2 mM EDTA, 400 mM NaCl (pH 7.2), and dialyzed for 20 h against the same buffer in double-sided biodialysers (Sialomed). The resulting tRNAPhe solution was polyamine-free (assayed by HPLC). The isotopically enriched spermines (Fig. 1) were added to the dialyzed tRNA solution to give final, 1 mM tRNAPhe, 8 mM polyamine mixtures. 1H-NMR spectra were recorded at 750 MHz at 5 °C. The water signal was suppressed by the jump return read pulse. The D period was set to 2.85 ms, the mixing period Tmix (t) was 300 ms and the d period was 45.3 ms; which placed the maximum of excitations at 12.1 ppm. The relaxation delay D1 was 1 s and the acquisition time was 0.182 s. The 1H transmitter frequency was on-resonance for H2O, and the 13C transmitter frequency was placed at 41 ppm. The 1H spectra was 22,522 Hz (30 ppm) and for each acquisition 2,048 complex ...

100D: CRYSTAL STRUCTURE OF THE HIGHLY DISTORTED CHIMERIC DECAMER R(C)D(CGGCGCCG)R(G)-SPERMINE COMPLEX-SPERMINE BINDING TO PHOSPHATE ONLY AND MINOR GROOVE TERTIARY BASE-PAIRING

The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naïve mice, GluA2-lacking AMPAR mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that inclusion of 100 µM Alexa dye, but not 10 µM, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship, from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors and 100 µM Alexa 594 did not alter the ...

Klempan TA, Rujescu D, Mérette C, Himmelman C, Sequeira A, Canetti L, et al. Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene in suicide. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(7):934-43. ...

Klempan TA, Rujescu D, Mérette C, Himmelman C, Sequeira A, Canetti L, et al. Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene in suicide. Am J Med Genet B Neuropsychiatr Genet. 2009;150B(7):934-43. ...

DNA binders were added in such concentrations to theU, that a previously calculated fraction of binding sites should be occupied (see here for calculation). We assumed to find a peak shift of the angles dependend on the added DNA binder concentration. The peaks for the tested DNA binding molecules spermine, ethidium bromide and DAPI as well as the negative control and the positive control (intrinsically twisted due to additional base pairs) are displayed in table 1. ,html, ,left,,font size=1,Table 1: ,/font, ,table cellspacing=0 cellpadding=6 align=center, ,tr bgcolor=#f5f5f5, ,td,,b,,/b,,/td,,td,,b,Number of particles,/b,,/td,,td,,b,Mean angle [degree],/b,,/td,,/td,,td,,b,Variance,/b,,/td,,/td,,/td, ,/tr, ,tr bgcolor=#f5f5f5, ,td,negative control,/td,,td,715,/td,,td,9.0,/td,,td,4.1,/td,, ,/tr, ,tr bgcolor=#f5f5f5, ,td,positive control (pretwisted),/td,,td,424,/td,,td,21.1,/td,,td,5.8,/td, ,/tr, ,tr bgcolor=#f5f5f5, ,td,Spermine 0.42 µM (in average one molecule per ...

100D: Crystal structure of the highly distorted chimeric decamer r(C)d(CGGCGCCG)r(G).spermine complex--spermine binding to phosphate only and minor groove tertiary base-pairing.

One of the recently developed polyamine (PA) analogues, N (1) ,N (11)-diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to ...

If a process while in the functioning condition has to watch for a useful resource (anticipate user enter or file to open, for example), it can be assigned the blocked state. The process point out is modified back again to waiting in the event the process not really should wait around (inside of a blocked condition ...

TY - JOUR. T1 - Growth arrest- and polyamine-dependent expression of spermidine/spermine N1-acetyltransferase in human tumor cells. AU - Ignatenko, Natalia. AU - Gerner, Eugene W.. PY - 1996/4. Y1 - 1996/4. N2 - Polyamines are essential for optimal cell growth. The regulation of polyamine biosynthetic, but not catabolic, enzymes has been studied in detail. Because intracellular polyamine contents depend on both synthesis and catabolism, we studied the regulation of spermidine/spermine N1- acetyltransferase (N1SSAT), the first enzyme in polyamine catabolism. Steady-state RNA levels of N1SSAT increased 3-5 fold as human colon tumor- derived HCT116 cells traversed the log phase and entered the plateau phase. Depletion of cellular polyamines, using α-difluoromethylornithine, caused a decrease in the steady-state levels of both the 1.3-kb N1SSAT transcript and its 3.5-kb precursor, without affecting the stability of either RNA. N1SSAT enzyme activity was low in cells with normal polyamine contents ...

Polyamine-biosynthesis activity is known to be negatively regulated by intracellular polyamine pools. Accordingly, treatment of cultured L1210 cells with 10 microM-spermine rapidly and significantly lowered ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities in a sequential manner. By contrast, treatment for 48 h with 10 microM of the unsaturated spermine analogue 6-spermyne lowered AdoMetDC activity, but not ODC activity. An initial decrease in ODC activity at 2 h was attributed to a transient increase in free intracellular spermidine and spermine brought about through their displacement by the analogue. Thereafter, ODC activity recovered steadily to control values as 6-spermyne pools increased and spermidine and spermine pools decreased owing to analogue suppression of AdoMetDC activity. The apparent ability of 6-spermyne to regulate AdoMetDC, but not ODC, activity suggests an interesting structure-function correlation and demonstrates that the typical ...

Increased arginase activity contributes to airway nitric oxide (NO) deficiency in cystic fibrosis (CF). Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in

TY - JOUR. T1 - The mechanism of the inhibitory effect of polyamines on the induction of nitric oxide synthase role of aldehyde metabolites. AU - Szabo, Csaba. AU - Southan, G. J.. AU - Thiemermann, C.. AU - Vane, J. R.. PY - 1994. Y1 - 1994. N2 - 1. We have recently found that in the presence, but not in the absence, of foetal calf serum, spermine inhibits the production of nitric oxide (NO) in cultured J774.2 macrophages stimulated with bacterial endotoxin (lipopolysaccharide, LPS) or with γ-interferon (IFN), showing that polyamines may act as suppressants of NO-mediated immune functions. Here, we have studied the mechanisms and the specificity of this inhibitory action. 2. Other polyamines, as well as spermine, inhibit the formation of NO in cultured J774.2 macrophages, with the order of potency being spermine , spermidine ,, putrescine = cadaverine. This inhibition of NO formation is not due to any cytotoxic effect of these agents for they neither reduced mitochondrial respiration nor ...

phdthesis{8467fc6f-8c20-4634-9e13-8c10c0b1c8ef, abstract = {Our research group has previously shown that treatment with the polyamine biosynthesis inhibitors a-difluoromethylornithine (DFMO) or amidinoindan-1-one 2´-amidinohydrazone (CGP 48664) inhibited S phase progression before any other cell cycle phase was affected. This study was undertaken to further investigate the role of polyamines in the regulation of S phase progression and DNA synthesis. I have found that treatment with the polyamine analog <i>N</i>¹,<i>N</i>¹¹-diethylnorspermine (DENSPM) also caused a prolongation of the S phase. The common denominator for DFMO, CGP 48664, or DENSPM treatment is a depletion of the cellular spermidine pool. CGP 48664 and DENSPM in addition deplete the spermine pool. CGP 48664 or DENSPM treatment prolonged the S phase more than did DFMO treatment. Thus, mainly spermine but also spermidine may have a function in S phase ...

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Two genes,LAT1andOCT1, are likely to be involved in polyamine transport in Arabidopsis. Endogenous spermine levels modulate their expression and determine the sensitivity to cadaverine. Arabidopsis sp

TY - JOUR. T1 - DNA structure control by polycationic species. T2 - Polyamine, cobalt aremines, and di-metallo transition metal chelates. AU - Rodger, Alison. AU - Sanders, Karen J.. AU - Hannon, Michael J.. AU - Meistermann, Isabelle. AU - Parkinson, Andrew. AU - Vidler, Daniel S.. AU - Haworth, Ian S.. PY - 2000. Y1 - 2000. N2 - Many polycationic species bind to DNA and induce structural changes. The work reported here is the first phase of a program whose long-term aim is to create a class of simple and inexpensive sequence-selective compounds that will enable enhanced DNA structure control for a wide range of applications. Three classes of molecule have been included in this work: the polyamine spermine (charge: 4+) and spermidine (charge: 3+) (which are known to induce a wide range of DNA conformational changes but whose binding modes are still not well understood); cobalt (III) ammine transition metal complexes as potential polyamine mimics and [Fe(H2O)6]3+; and the first member of a new ...

SAT1 - SAT1 (untagged)-Human spermidine/spermine N1-acetyltransferase 1 (SAT1), transcript variant 1 available for purchase from OriGene - Your Gene Company.

We have studied the UV-vis absorption and chiroptical properties, binding affinity and photostability of a conjugated positively charged butadiyne-linked Zn(ii) porphyrin dimer bound to DNA sequence poly(dG-dC)2. Right-handed B-DNA, spermine-induced Z-DNA and Co(iii)-induced Z-DNA have been explored. Resonan

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

Because of the presence of another spermine synthase gene in Arabidopsis, SPMS, all sac acl5 mutants should still be able to produce spermine. This raised the possibility that the spermine produced by SPMS could function in the ACL5-mediated regulatory pathways in sac mutants. However, we found that all four sac mutants can also suppress the acl5 phenotype in an acl5 spms background (Fig. 4B), indicating that the recovery of stem growth does not require spermine in these sac mutants. This result is consistent with the observation that, unlike the HS-ACL5 construct, which can restore the acl5 phenotype in a heat-shock-dependent manner (Hanzawa et al., 2000), the HS-SPMS construct had no effect on the growth of acl5 plants carrying the construct (see Fig. S2B in the supplementary material). Determination of the subcellular localization of ACL5 and SPMS, and/or the identification of an ACL5-interacting protein, will be needed for further understanding of the functional difference between these two ...

2,4-dihydroxyphenylacetylasparaginyl spermine: analog of Joro spider toxin; suppresses the excitatory postsynaptic potentials; structure given in first source

Spermine phosphate hexahydrate/ACM58298978 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.

Spermidine is a natural polyamine found in many foods you likely eat; mushrooms, broccoli, apples, nuts, soy, aged cheese & much more.

Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.

摘要. Unlocking the endosome allows the release of siRNAs into the cytoplasm following the cellular uptake of nanoparticles made up of siRNAs and polyspermine imidazole-4,5-imine. In their Communication on page 7938 ff., T. Jin and co-workers show that a polymer of spermine with a pH-sensitive linkage degrades, upon entry into the endosome, into spermine and a nontoxic metabolite. Assays in cells and mice showed effective gene silencing by the polymer-packaged siRNAs without cytotoxicity.. ...

The Golm Metabolome Database (GMD) facilitates the search for and dissemination of mass spectra from biologically active metabolites quantified using GC-MS.

The enzyme is not the biomarker. The biomarker is the product (metabolite) of the enzymatic reaction. An over-expressed enzyme related to cancer will produce many thousands of times more metabolite, thereby exponentially increasing the signal-to-background-noise ratio. The result is an amplified biomarker that acts like beacon for early detection that no traditional biomarker can match.. BioMark has identified one such enzyme that is over-expressed in most types of cancer cells, therefore giving them the ability to detect many tumors. This enzyme is called spermidine/spermine acetyltransferase (SSAT) and it converts an FDA-approved drug called amantadine into an acetylated form called N-acetylamantadine. N-acetylamantadine is produced in high amounts in cancer cells and is easily detected in urine in a cost-effective manner. ...

It is well known that the antitumor effects of chemotherapeutic drugs are at least partially mediated by apoptosis. DENSPM represents the first polyamine analogue to undergo clinical evaluation against solid tumors. To design second generation analogues and to more effectively deploy DENSPM, the mechanisms underlying drug sensitivity need to be understood. We previously reported that DENSPM could cause G1 arrest followed by a delayed apoptotic response in certain melanoma cells (7) and rapid apoptosis mediated by cytochrome c release and caspase activation in others (8) . In another study, 4 we showed that SSAT-dependent down-regulation of the apoptotic inhibitory protein, survivin, is causally involved in the apoptosis of melanoma cells. Here, we additionally investigate the role of MAPK activation in determining cellular responses to this novel class of anticancer agents.. The present studies were guided by a gene-profiling lead indicating that the transcription factor EGR-1 was potently ...

In general ma uit la gama si fac ceva in spiritul originalul pentru ca sunt prea lenes sa invat nota cu nota. In legatura cu compozitia origniala, am idei dar nu am trupa datorita localitatii in care stau. Sper ca atunci cand voi pleca de aici sa imi fac trupa si sa pot sa cant chestiile originale sau pana atunci sper sa invat sa lucrez cu programe de editat/creat muzica si poate o sa reusesc sa fac un fel de backing track pentru ideile originale. Multumesc de incurajari ...

Au fost niste creatii superbe dar si asemanari intre rochii foarte mari.Am zis sa postez cateve din rochiile care s-au purtat pentru ca unele dintre ele sunt chiar uimitoare.Am sa traduc parerile criticilor deoarece sunt in limba engleza.Sper sa va placa ...

Sper ca magia care ne inconjoara de Craciun sa dureze tot anul in jurul fiecaruia dintre noi si sa ne aduca fericirea si linistea pe care ne-o dorim cu totii ...

A widespread increase in SpmS (spermine synthase) activity has been produced in transgenic mice using a construct in which the human SpmS cDNA was placed under the control of a composite CMV-IE (cytomegalovirus immediate early gene) enhancer-chicken β-actin promoter. Four separate founder CAG/SpmS mice were studied. Transgenic expression of SpmS was found in all of the tissues examined, but the relative SpmS activities varied widely according to the founder animal and the tissue studied. Very large increases in SpmS activity were seen in many tissues. SpdS (spermidine synthase) activity was not affected. Although there was a statistically significant decline in spermidine content and increase in spermine, the alterations were small compared with the increase in SpmS activity. These results provide strong support for the concept that the levels of the higher polyamines spermidine and spermine are not determined only by the relative activities of the two aminopropyltransferases. Other factors ...

TY - JOUR. T1 - Intracellular polyamines mediate inward rectification of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. AU - Donevan, Sean D.. AU - Rogawski, Michael A. PY - 1995/9/26. Y1 - 1995/9/26. N2 - α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are Ca2+-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca2+-permeable inwardly rectifying AMPA receptor currents. Inward rectification in these neurons was lost with intracellular dialysis and was not present in excised outside-out patches but was maintained in perforated-patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturally occurring polyamines spermine and spermidine in the recording pipette prevented loss of rectification in both whole-cell and excisedpatch ...

article{64ec06c7-2e42-4bdc-9fdd-bff9b8f477a3, abstract = {The macroscopic phase behavior and other physicochemical properties of dilute aqueous mixtures of DNA and the cationic surfactant hexadecyltrimethylammounium bromide (CTAB), DNA and the polyamine spermine, or DNA, CTAB, and (2-hydroxypropyl)-β-cyclodextrin (2HPβCD) were investigated. When DNA is mixed with CTAB we found, with increasing surfactant concentration, (1) free DNA coexisting with surfactant unimers, (2) free DNA coexisting with aggregates of condensed DNA and CTAB, (3) a miscibility gap where macroscopic phase separation is observed, and (4) positively overcharged aggregates of condensed DNA and CTAB. The presence of a clear solution beyond the miscibility gap cannot be ascribed to self-screening by the charges from the DNA and/or the surfactant; instead, hydrophobic interactions among the surfactants are instrumental for the observed behavior. It is difficult to judge whether the overcharged mixed aggregates represent an ...

Microbial metabolites and colon cancer. Colon cancers that present on the right versus the left side of the colon have significantly worse prognosis for the patient. A recent discovery revealed that right-sided colon cancers (RCCs) harbor mucosal bacterial biofilms, whereas left-sided colon cancers (LCC) are predominantly devoid of biofilms. These biofilms are associated with increased cellular proliferation and inflammation even in normal colon tissues. Using mass spectrometry-based metabolomics, we investigated the metabolism of colon cancers with and without biofilms, and observed a correlation between increased diacetylspermine production and biofilm presence on RCCs. Using antibiotic treatment, IHC, and stable isotope-assisted metabolomics we showed that diacetylspermine is an end product of polyamine metabolism produced by bacterial biofilms. We thus hypothesized that microbiota use host-derived polyamines to form biofilms. It is still not known why biofilms only form only on RCC, but it ...

Background Snyder-Robinson Syndrome (SRS) is an X-linked intellectual disability disorder also characterized by osteoporosis, scoliosis, and dysmorphic facial features. It is caused by mutations in SMS, a ubiquitously expressed gene encoding the polyamine biosynthetic enzyme spermine synthase. We hypothesized that the tissue specificity of SRS arises from differential sensitivity to spermidine toxicity or spermine deficiency. Methods We performed detailed clinical, endocrine, histopathologic, and morphometric studies on two affected brothers with a spermine synthase loss of function mutation (NM_004595.4:c.443A | G, p.Gln148Arg). We also measured spermine and spermidine levels in cultured human bone marrow stromal cells (hBMSCs) and fibroblasts using the Biochrom 30 polyamine protocol and assessed the osteogenic potential of hBMSCs. Results In addition to the known tissue-specific features of SRS, the propositi manifested retinal pigmentary changes, recurrent episodes of hyper- and hypoglycemia,

Flavoenzyme which catalyzes the oxidation of N(1)-acetylspermine to spermidine and is thus involved in the polyamine back-conversion. Can also oxidize N(1)-acetylspermidine to putrescine. Substrate specificity: N(1)-acetylspermine = N(1)-acetylspermidine > N(1),N(12)-diacylspermine >> spermine. Does not oxidize spermidine. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs.

Concerning the pool of discriminant amino acids and biogenic amines, the most striking feature is the reduced concentration of spermidine and spermine in the POAG group compared to controls. Both of these metabolites are known to have an important role in optic nerves.32 Spermidine mediates protection against oxidative damage and has a neuroprotective effect on RGCs after optic nerve injury in adult mice.33 In a mouse model of normal-tension glaucoma, spermidine has been shown to prevent the neurodegeneration of RGCs.34 Interestingly, Kim et al.29 have reported decreased concentrations of spermidine and spermine in the blood of aged mice, as also found in several other organisms.35 It is worth noting that methionine and arginine, which have increased concentrations in the metabolomic signature of POAG, are both precursors of the biosynthesis of spermidine and spermine, with methionine being a methyl radical donor. Thus, the senescence-related perturbation of spermidine and spermine biosynthesis ...

Not too long ago, there is a report that NNMT expression is improved in WAT and liver of overweight and diabetic mice. Nnmt knockdown in WAT and liver protects against diet program-induced being overweight by maximizing cellular strength expenditure. NNMT inhibition will increase adipose SAM and NAD1 stages and up regulates ODC and SSAT action as effectively as Agi-5198expression, owing to the consequences of NNMT on histone H3K4 methylation. Direct proof for improved polyamine flux resulting from NNMT inhibition consists of elevated urinary excretion and adipocyte secretion of diacetylspermine. NNMT inhibition raises oxygen usage in an ODC-, SSAT- and PAO-dependent manner ...

Just lately, there is a report that NNMT expression is increased in WAT and liver of overweight and diabetic mice. Nnmt knockdown in WAT and liver protects in opposition to diet plan-induced obesity by enhancing cellular power expenditure. NNMT inhibition boosts adipose SAM and NAD1 ranges and up regulates ODC and SSAT exercise as properly as Agi-5198expression, owing to the consequences of NNMT on histone H3K4 methylation. Immediate evidence for elevated polyamine flux ensuing from NNMT inhibition involves elevated urinary excretion and adipocyte secretion of diacetylspermine. NNMT inhibition boosts oxygen consumption in an ODC-, SSAT- and PAO-dependent manner ...

Just lately, there is a report that NNMT expression is increased in WAT and liver of overweight and diabetic mice. Nnmt knockdown in WAT and liver protects in opposition to diet plan-induced obesity by enhancing cellular power expenditure. NNMT inhibition boosts adipose SAM and NAD1 ranges and up regulates ODC and SSAT exercise as properly as Agi-5198expression, owing to the consequences of NNMT on histone H3K4 methylation. Immediate evidence for elevated polyamine flux ensuing from NNMT inhibition involves elevated urinary excretion and adipocyte secretion of diacetylspermine. NNMT inhibition boosts oxygen consumption in an ODC-, SSAT- and PAO-dependent manner ...

Polyamines (PAs) are involved in regulation of cell growth and cellular survival by interacting with processes like translation, transcription or ion transport. It is described that polyamines can induce apoptosis in mesenchymal cell lines. The aim of our study was to analyze whether the physiological PAs (putrescine, spermidine or spermine) or the PA-derivate deoxyspergualin (DSG), a novel immunosuppressant, induce apoptosis in immunocompetent cells. Furthermore, we wanted to investigate which molecular mechanisms are involved in the execution of the cell death program. By means of flow cytometric analysis we found an induction of apoptosis by spermine (Spm) and DSG in quiescent and activated PBMCs, PHA generated lymphoblasts, and various tumor cell lines (Jurkat, SKW-3, U937). Moreover, DSG and Spm triggered apoptosis in human Fas-deficient cells and in cell lines MV4.11. and RS4.11., which are described to be resistant to apoptosis induction by many conventional chemotherapeutic agents. ...

Milhinhos, A., Prestele, J., Bollhöner, B., Matos, A., Vera-Sirera, F., Rambla, J. L., Ljung, K., Carbonell, J., Blázquez, M. A., Tuominen, H. and Miguel, C. M. (2013), Thermospermine levels are controlled by an auxin-dependent feedback loop mechanism in Populus xylem. The Plant Journal, 75: 685-698. doi: 10.1111/tpj.12231 ...

This study aimed to determine the effects of dietary spermine supplementation on the inflammatory response and immune function of the thymus and spleen in piglets. Eighty suckling piglets were randomly assigned to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight) or restricted nutrient intake supplemented with normal saline for 7 h or 3, 6 and 9 days in pairs. Regardless of treatment time, spermine supplementation decreased (p , 0.05, compared with the controls) the following: (1) tumour necrosis factor α (TNF-α), interleukin (IL)-1β, 2 and 6, and interferon (IFN)-γ levels in serum; (2) gene expression of cluster of differentiation 8 and integrin beta-2 in the thymus and spleen and the lymphocyte function-associated antigen 1 in the thymus; (3) mRNA levels of TNF-α, IL 1β, 2, 6, and 12, IFN-γ and inducible nitric oxide synthase in the thymus and spleen, as well as IL-8 in the spleen; and (4) eukaryotic IF4E-binding protein 1, Janus kinase 2, signal transducer ...

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Published on Oct 1, 2016 Dr. Rhonda Patrick speaks with Dr. Valter Longo, a professor of gerontology and biological sciences and director of the longevity institute at the University of Southern California. Dr. Longo has made huge contributions to the field of aging, including the role of fasting and diet in longevity and healthspan in humans as well as metabolic fasting therapies for the treatment of human diseases. In this conversation, Rhonda and Valter discuss... • The effects of prolonged fasting, which refers to 2-3 day fasting intervals in mice and 4-5 days in humans. • Dr. Longos work on the fasting-mimicking diet, which is 5 day restricted diet that is meant to simulate some of the biological effects of prolonged fasting while still allowing some food. • How clinical trials have demonstrated efficacy for this diet for type 2 diabetes, multiple sclerosis, and cancer patients. • Fasting as an inducer of differential stress resistance, where it can simultaneously make cancer cells ...

Gene expression during development is regulated both transcriptionally and translationally; however, relatively few examples of translational regulation are known. On p. 3575, Imai and colleagues describe for the first time how an upstream open reading frame (uORF) mediates translational control during plant development. Loss-of-function mutants of Arabidopsis ACAULIS 5 (ACL5), which encodes spermine synthase, have a dwarf phenotype because of a defect in stem elongation. To find out how ACL5 regulates stem elongation, the researchers isolated a dominant suppressor mutant of the acl5 phenotype - sac51-d. They show that sac51-d disrupts a short uORF of SAC51, which encodes a bHLH transcription factor. Other experiments indicate that this disruption might increase the translation of SAC51. Thus, the researchers suggest that the uORF-encoded protein normally prevents the initiation of SAC51 translation, and that ACL5 acts directly or indirectly (possibly through spermines effects on protein ...

Mixed NMDA glutamate receptor agonist/antagonist at the polyamine site. Neuroprotective effects have been observed at high concentrations (1 mM), while neurotoxicity is observed at lower concentrations. It enhances agonist effectiveness at the strychnine-insensitive glycine site. Plays a role in cellular proliferation and differentiation; inhibits neuronal nitric oxide synthase (nNOS). ...

Gamma-glutamylputrescine synthetase PuuA; Involved in the breakdown of putrescine via the biosynthesis of gamma-L-glutamylputrescine. It is able to use several diamines, spermidine and spermine. Absolutely essential to utilize putrescine as both nitrogen and carbon sources and to decrease the toxicity of putrescine, which can lead to inhibition of cell growth and protein synthesis; Belongs to the glutamine synthetase ...

The objective of this project was to synthesize a protected spermidine derivative, which is a polyamine derivative. The spermidine that was to be synthesised is a N8 protected spermidine derivative.

Approximately 18-45 patients with Hepatocellular Carcinoma (HCC) will be treated with DENSPM at approximately 5 centers in the United States. First, we

Circular Dichroism, DNA, Absorption, Nickel, Z-dna, B-dna, Report, Spermine, Cadmium, Concentrations, Cytosine, Guanine, Fluorescence, Ionic Strength, Oligonucleotides, Adenine, Electronic, Light, Porphyrins, Sensitivity

Polyplus-transfection® has developed a novel class of cationic modified oligonucleotides (OLIGOPLUS) that require no delivery agent as they act as cell-penetrating oligonucleotides. This is achieved by grafting cationic spermine units onto the oligonucleotide to create a positively charged oligocation-oligonucleotide conjugate.

eBiochemicals provides information on the O,O-Dimethyl phosphoramidothioate(O,O-Dimethyl thiophosphoramidate;o,o-dimethyl phosphoramidothioate;O,O-Dimethyl Phosphoroamido Thioate;O,O-dimethylamidothiophosphate;O,O-DimethylPhosphoramidothionate;O,O-DIMETHYL THIOPHORAMIDOTHIONATE;E-118 amide;SPERMINE(RG)): structure, NMR,MS,IR,spectral data, msds, molecular formula, cas, physical and chemical properties, and suppliers.

Buna, ma numesc Leonora si sunt pasionata de flori.Sper sa ma primiti si pe mine printre voi, fiind noua pe forum, multumesc frumos.