BACKGROUND & AIMS: :The polyamine spermine is transported into the mitochondrial matrix by an electrophoretic mechanism having as driving force the negative electrical membrane potential (ΔΨ). The presence of phosphate increases spermine uptake by reducing ΔpH and enhancing ΔΨ. The transport system is a specific uniporter constituted by a protein channel exhibiting two asymmetric energy barriers with the spermine binding site located in the energy well between the two barriers. Although spermine transport is electrophoretic in origin, its accumulation does not follow the Nernst equation for the presence of an efflux pathway. Spermine efflux may be induced by different agents, such as FCCP, antimycin A and mersalyl, able to completely or partially reduce the ΔΨ value and, consequently, suppress or weaken the force necessary to maintain spermine in the matrix. However this efflux may also take place in normal conditions when the electrophoretic accumulation of the polycationic polyamine induces a sufficient drop in ΔΨ able to trigger the efflux pathway. The release of the polyamine is most probably electroneutral in origin and can take place in exchange with protons or in symport with phosphate anion. The activity of both the uptake and efflux pathways induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and outer compartment. Thus, this event has a significant role on mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis.

背景与目标： ：多胺精胺通过具有负膜电位（ΔΨ）作为驱动力的电泳机制被转运到线粒体基质中。磷酸盐的存在通过降低ΔpH和增强ΔΨ来增加精胺的摄取。转运系统是一个特殊的单向转运蛋白，由一个蛋白通道构成，该通道显示两个不对称的能垒，其中精胺结合位点位于两个能垒之间的能阱中。尽管精胺转运的起源是电泳，但对于外排途径的存在，其积累并不遵循能斯特方程。精胺外排可以由不同的试剂诱导，例如FCCP，抗霉素A和巯基，其能够完全或部分降低ΔΨ值，并因此抑制或减弱将精胺维持在基质中所需的力。然而，当聚阳离子多胺的电泳积累引起足以触发流出途径的ΔΨ下降时，这种流出也可能在正常条件下发生。多胺的释放很可能是电子中性的，可以与质子交换或与磷酸根阴离子共存。摄取和流出途径的活性都诱导精胺跨过线粒体膜的连续循环，其速率在将内和外隔室中的精胺浓度强加时可能是显着的。因此，该事件对线粒体通透性转变调节具有重要作用，因此对内在凋亡的触发也具有重要作用。

BACKGROUND & AIMS: :Spermine and spermidine are polyamines (PA) naturally present in all organisms, in which they have important physiological functions. However, an excess of PA has been associated with health risks. PA accumulates at quite high concentrations in some foods, but a quantitative assessment of the risk they pose has been lacking. In the present work, the cytotoxicity of spermine and spermidine was evaluated using an in vitro human intestinal cell model, and employing real-time cell analysis. Both spermine and spermidine showed a dose-dependent cytotoxic effect towards the cultured cells, with necrosis the mode of action of spermidine and perhaps also that of spermine. Spermine was more cytotoxic than spermidine, but for both PA the concentrations found to be toxic were above the maximum at which they have been found in food. The present results do not, therefore, support the idea that spermine or spermidine in food is harmful to healthy people.

背景与目标： ：精胺和亚精胺是所有生物中天然存在的多胺（PA），在其中具有重要的生理功能。但是，PA过多与健康风险有关。 PA在某些食物中会以很高的浓度积累，但一直缺乏对它们造成的风险的定量评估。在目前的工作中，使用体外人肠道细胞模型并采用实时细胞分析法评估了精胺和亚精胺的细胞毒性。精胺和亚精胺均对培养的细胞显示出剂量依赖性的细胞毒性作用，坏死了亚精胺和也许还有精胺的作用方式。精胺比亚精胺具有更高的细胞毒性，但是对于两种PA来说，被发现有毒的浓度都高于在食物中发现的最高浓度。因此，目前的结果并不支持食物中的亚精胺或亚精胺对健康人有害的观点。

BACKGROUND & AIMS: :Naturally occurring polyamines putrescine, cadaverine, spermidine, and spermine are analogues of the species-specific long-chain polyamines found in diatoms. Scanning electron microscopy and energy-dispersive spectroscopy show that the reactions of a soluble Ti(IV) precursor with spermidine and spermine, but not putrescine or cadaverine, produce nanostructured irregular polyhedra of titanium oxide. At 25 degrees C, the average size of the particles formed with spermidine is 400 +/- 150 nm, and with spermine, 140 +/- 50 nm. Although the particles are X-ray amorphous at room temperature, annealing studies reveal that the particles adopt crystallinity at higher temperatures characteristic of anatase (TiO2). The major portion of the biopolyamines is not coprecipitated with the solid but is left in solution. Kinetic measurements reveal an initial fast step followed by two slower phases of reaction. At 25 degrees C, k(1obs) and k(2obs) for the reaction with spermidine are 5 x 10(-3) s(-1) and 3.6 x 10(-4) s(-1), respectively, and for spermine, 4.8 x 10(-3) s(-1) and 4.2 x 10(-4) s(-1), respectively. Taken together, the data suggest spermidine and spermine are biocatalysts for the precipitation of nanostructured titanium oxide.

背景与目标： 天然存在的多胺腐胺，尸胺，亚精胺和精胺是硅藻中特定物种的长链多胺的类似物。扫描电子显微镜和能量色散光谱表明，可溶性Ti（IV）前体与亚精胺和亚精胺的反应，而不是腐胺或尸胺的反应，生成纳米结构的不规则二氧化钛。在25℃下，由亚精胺形成的颗粒的平均尺寸为400±150nm，与亚精胺形成的颗粒的平均尺寸为140±50nm。尽管颗粒在室温下是X射线无定形的，但退火研究表明，颗粒在较高温度下具有锐钛矿（TiO2）的特征结晶性。生物多胺的大部分不与固体共沉淀，而是留在溶液中。动力学测量揭示了最初的快速步骤，随后是两个较慢的反应阶段。在25摄氏度下，与亚精胺反应的k（1obs）和k（2obs）分别为5 x 10（-3）s（-1）和3.6 x 10（-4）s（-1），对于精胺分别为4.8 x 10（-3）s（-1）和4.2 x 10（-4）s（-1）。两者合计，数据表明亚精胺和亚精胺是用于沉淀纳米结构二氧化钛的生物催化剂。

BACKGROUND & AIMS: :The spermine analogue N1,N4-bis-(2,3-butadienyl)-1,4-butanediamine (MDL-72527), an effective inhibitor of polyamine oxidases (PAOs), triggers a systemic response in tomato (Solanum lycopersicum L.) exposed to sublethal (100mM) and lethal (250mM) NaCl concentrations. The accumulation of free polyamines (PAs), the terminal oxidation of PAs by diamine oxidases (DAOs) and PAOs, and the production of H2O2 by PA oxidases depends on the intensity of salt stress. Spermidine and spermine content increased significantly under sublethal salt concentrations, but remained low under lethal salt stress. Along with increased expression of the selected SlDAO1 and SlPAO1 genes in the leaves and roots, respectively, DAO and PAO activities and their product, H2O2, increased and initiated cell death by irreversible loss of electrolytes at 250mM NaCl. MDL-72527 significantly increased spermine, spermidine and/or putrescine contents as a result of reduced activity of PA oxidases; furthermore, it inhibited H2O2 and NO production during salt treatment. These results indicate that PAO contributed to H2O2 and NO production under salt stress, and the terminal activities of DAO and PAO play a role in cell death induction at 250mM NaCl. However, the inhibition of PAO by MDL-72527 does not increase the salt tolerance of plants, since electrolyte leakage increased significantly in the presence of the inhibitor.

背景与目标： ：精胺类似物N1，N4-双-（2,3-丁二烯基）-1,4-丁二胺（MDL-72527）是多胺氧化酶（PAOs）的有效抑制剂，可引发番茄（茄属植物Solanum lycopersicum L. ）暴露于亚致死浓度（100mM）和致死浓度（250mM）的NaCl中。游离多胺（PAs）的积累，二胺氧化酶（DAOs）和PAOs对PAs的最终氧化作用以及PA氧化酶产生H2O2取决于盐胁迫的强度。在亚致死盐浓度下，亚精胺和亚精胺含量显着增加，但在致死盐胁迫下，亚精胺和亚精胺含量却保持较低水平。分别在叶片和根中增加所选的SlDAO1和SlPAO1基因的表达，DAO和PAO的活性及其产物H2O2在250mM NaCl下通过不可逆的电解质损失而增加并引发细胞死亡。由于PA氧化酶活性降低，MDL-72527显着增加了精胺，亚精胺和/或腐胺的含量；此外，它还抑制了盐处理过程中的H2O2和NO生成。这些结果表明，PAO促进了盐胁迫下H2O2和NO的产生，而DAO和PAO的末端活性在250mM NaCl诱导细胞死亡中起作用。但是，通过MDL-72527抑制PAO不会增加植物的耐盐性，因为在存在抑制剂的情况下电解质的泄漏会明显增加。

BACKGROUND & AIMS: :Spermidine/spermine N(1)-acetyltransferase (SSAT) regulates intracellular polyamine levels by catabolizing spermidine and spermine which are essential for cell proliferation and differentiation. Hematological characterization of SSAT overexpressing mice (SSAT mice) revealed enhanced myelopoiesis and thrombocytopoiesis leading to increased amounts of myeloid cells in bone marrow, peripheral blood, and spleen compared to wild-type animals. The level of SSAT activity in the bone marrow cells was associated with the bone marrow cellularity and spleen weight which both were significantly increased in SSAT mice. The result of bone marrow transplantations indicated that both the intrinsic SSAT overexpression of bone marrow cells and bone marrow microenvironment had an impact on the observed hematopoietic phenotype. The Lineage-negative Sca-1(+) c-Kit(+) hematopoietic stem cell (HSC) compartment in SSAT mice, showed enhanced proliferation, increased proportion of long-term HSCs and affected expression of transcription factors associated with lineage priming and myeloid differentiation. The proportions of common myeloid and megakaryocytic/erythroid progenitors were decreased and the proportion of granulocyte-macrophage progenitors was increased in SSAT bone marrow. The data suggest that SSAT overexpression and the concomitantly accelerated polyamine metabolism in hematopoietic cells and bone marrow microenvironment affect lineage commitment and lead to the development of a mouse myeloproliferative disease in SSAT mice.

背景与目标： ：亚精胺/亚精胺N（1）-乙酰基转移酶（SSAT）通过分解代谢亚精胺和亚精胺来调节细胞内多胺水平，这对于细胞增殖和分化至关重要。与野生型动物相比，过表达SSAT的小鼠（SSAT小鼠）的血液学特征表明，骨髓生成和血小板生成增强，导致骨髓，外周血和脾脏中的髓样细胞数量增加。骨髓细胞中SSAT活性水平与SSAT小鼠中的骨髓细胞密度和脾脏重量均显着相关。骨髓移植的结果表明，固有的SSAT骨髓细胞过表达和骨髓微环境都对观察到的造血表型有影响。 SSAT小鼠中的沿袭阴性Sca-1（）c-Kit（）造血干细胞（HSC）隔室显示出增强的增殖，长期HSC的比例增加以及与沿袭引发和髓样分化相关的转录因子表达受到影响。 SSAT骨髓中常见髓样和巨核细胞/类红细胞祖细胞的比例降低，而粒细胞-巨噬细胞祖细胞的比例增加。数据表明，造血细胞和骨髓微环境中SSAT的过表达以及多胺代谢的同时加速会影响血统，并导致SSAT小鼠发生骨髓增生性疾病。

BACKGROUND & AIMS: :Spermine at a concentration of 0.001 m initiated the reversion of penicillin-induced L-phase growth of Haemophilus influenzae to bacillary growth on penicillin L-phase medium. Reversion of L-phase colonies to bacillary colonies required 3 to 5 days. This spermine reversal of variant growth also occurred on penicillin induction medium in the presence of concentrations of tetracycline, erythromycin, and chloramphenicol that were not bactericidal for L-phase or bacillary inocula until 48 or more hr. Spermine was without protective effect against streptomycin and kanamycin, which were, in combination with penicillin, bactericidal at 24 hr. Spermine protection of L-phase variants against antibiotic toxicity was, therefore, related to initiation (by spermine) or bacillary growth from round bodies that survived for 24 or more hr at bacteriostatic levels of antibiotic.

背景与目标： ：浓度为0.001 m的精胺可引发青霉素诱导的流感嗜血杆菌L期生长向青霉素L期培养基上的细菌生长逆转。将L期菌落恢复为细菌菌落需要3至5天。在青霉素诱导培养基上还存在这种浓度的精胺逆转，其存在的四环素，红霉素和氯霉素的浓度直到48小时或更长时间才对L期或杆菌接种具有杀菌作用。精胺对链霉素和卡那霉素没有保护作用，而链霉素和卡那霉素与青霉素联用则在24小时杀菌。因此，精氨酸对L期变体的抗抗生素毒性保护与从（通过精胺）或在抑菌水平上存活24小时或更长时间的圆形物体的细菌生长有关。

BACKGROUND & AIMS: :The interaction of chitosan and polyamines (PAs) could be involved mitigating drought stress in white clover (Trifolium repens L.). This research aimed to determine the effect of chitosan and PAs, and co-application of chitosan and PAs on improving drought tolerance associated with growth, phytohormones, polyamines and antioxidant metabolism. Plants were pretreated with or without 1gL-1 chitosan, 0.5mM spermine, or 1gL-1 chitosan+0.5mM spermine, then subjected to drought induced by polyethylene glycol (PEG) 6000 (-0.5MPa) in growth chambers for 14 days. Exogenous chitosan and spermine improved the level of PAs by regulating arginine decarboxylases, S-adenosyl methionine decarboxylase, copper-containing amine oxidase and polyamine oxidase activity, and expression of the genes encoding these enzymes under drought. Application of exogenous chitosan improved ABA content under normal and drought conditions. In addition, chitosan and spermine significantly enhanced the levels of cytokinin and GA, but reduced IAA levels during drought stress. Exogenous chitosan and spermine improved antioxidant defence, including enzyme activity, gene expression and the content of ascorbate and glutathione compounds, leading to a decline in superoxide anion radicals, H2O2 and malondialdehyde, effectively mitigating drought-induced oxidative damage. Other protective metabolites, such as total phenols and flavonoids, increased considerably under application of chitosan and spermine. These results suggest that chitosan-induced drought tolerance could be involved in PA metabolism, changes in endogenous phytohormones and antioxidant defence in white clover. Co-application of chitosan and spermine was more effective than either chitosan or spermine alone in mitigating drought stress.

背景与目标： ：壳聚糖和多胺（PAs）的相互作用可能与减轻白三叶草（Trifolium repens L.）的干旱胁迫有关。这项研究旨在确定壳聚糖和PA的作用，并共同应用壳聚糖和PA在改善与生长，植物激素，多胺和抗氧化剂代谢有关的耐旱性方面。用或不使用1gL-1壳聚糖，0.5mM精胺或1gL-1壳聚糖0.5mM精胺对植物进行预处理，然后在生长室中使其受到聚乙二醇（PEG）6000（-0.5MPa）诱导的干旱14天。外来的壳聚糖和精胺可通过调节精氨酸脱羧酶，S-腺苷甲硫氨酸脱羧酶，含铜的胺氧化酶和聚胺氧化酶的活性以及干旱条件下编码这些酶的基因的表达来改善PA的水平。在正常和干旱条件下，外源壳聚糖的应用可提高ABA含量。此外，壳聚糖和精胺显着提高了细胞分裂素和GA的水平，但在干旱胁迫下降低了IAA的水平。外源壳聚糖和精胺提高了抗氧化防御能力，包括酶活性，基因表达以及抗坏血酸和谷胱甘肽化合物的含量，导致超氧阴离子自由基，H2O2和丙二醛的减少，有效减轻了干旱引起的氧化损伤。在施用壳聚糖和精胺后，其他保护性代谢物（例如总酚和类黄酮）显着增加。这些结果表明，壳聚糖诱导的干旱耐受性可能与白三叶草的PA代谢，内源性植物激素的变化和抗氧化防御有关。共同使用壳聚糖和精胺比单独使用壳聚糖或精胺在缓解干旱胁迫方面更有效。

BACKGROUND & AIMS: :The association of spermine(4+) (Spm(4+)), Mg(2+) and monovalent (M(+)) ions with DNA in crystal form, have been studied using grand canonical Monte Carlo (GCMC) and molecular dynamics (MD) computer simulations. GCMC calculations were used to calculate the distribution of Spm(4+), Mg(2+), and M(+) between the equilibrating solvent and the DNA crystal under conditions mimicking the crystal-growing protocols reported in a number of recent X-ray diffraction studies of DNA oligomers. The GCMC simulations show that the composition of ions neutralizing the negative charge of DNA can vary in a broad range. The GCMC simulations were used to provide appropriate conditions for subsequent 6 ns constant pressure and temperature MD simulations of DNA in a typical crystalline environment consisting of three DNA double helix decamers in a periodic hexagonal cell, containing 1200 water molecules, eight Spm(4+), 32 Na(+) and four Cl(-) ions. Based on the simulation results, it seems possible to give an explanation why spermine molecules are usually not detected in X-ray studies in spite of their high concentration in the preparatory samples used as the crystallizing agent. It appears that this flexible polyamine molecule has several binding modes, interacting in fairly irregular manner with different sites on DNA and showing no regular ordering in the DNA crystals. Ions of Na(+) and Spm(4+) compete with each other and with water molecules in binding to bases in the minor groove and they influence the structure of the DNA hydration shell in different ways.

背景与目标： ：使用大正则蒙特卡罗（GCMC）和分子动力学（MD）研究了精胺（4）（Spm（4）），Mg（2）和一价（M（））离子与晶体形式的DNA的缔合计算机模拟。在许多最近的X射线衍射研究中报道的模拟晶体生长方案的条件下，使用GCMC计算来计算平衡溶剂和DNA晶体之间Spm（4），Mg（2）和M（）的分布DNA低聚物。 GCMC模拟表明，中和DNA负电荷的离子组成可以在很宽的范围内变化。在典型的晶体环境中，GCMC模拟被用来为随后的6 ns恒压和温度MD模拟提供适当的条件，该模拟环境由周期性六边形细胞中的三个DNA双螺旋十面体组成，包含六个1200个水分子，八个Spm（4）， 32 Na（）和四个Cl（-）离子。根据模拟结果，似乎可以解释为什么尽管在用作结晶剂的制备样品中浓度较高，但通常在X射线研究中未检出精胺分子。似乎该柔性多胺分子具有几种结合模式，以相当不规则的方式与DNA上的不同位点相互作用，并且在DNA晶体中没有规则的顺序。 Na（）和Spm（4）离子相互竞争，并且与水分子竞争，与小沟中的碱基结合，它们以不同的方式影响DNA水化壳的结构。

BACKGROUND & AIMS: :Ornithine decarboxylase (ODC) is subject to feedback regulation by the polyamines. Thus, addition of putrescine, spermidine or spermine to cells causes inhibition of ODC mRNA translation. Putrescine and spermine are readily converted into spermidine. Therefore, it is conceivable that the inhibition of ODC synthesis observed in putrescine- and spermine-supplemented cells is instead an effect of spermidine. To examine this possibility we have used two analogs of putrescine and spermine, namely 1,4-dimethylputrescine and 5,8-dimethylspermine, which cannot be converted into spermidine. Both analogs were found to inhibit the incorporation of [35S]methionine into ODC protein to approximately the same extent, suggesting that putrescine as well as spermine exert a negative feedback control of ODC mRNA translation in the cell. In addition to suppressing ODC synthesis, both analogs were found to increase the turnover rate of the enzyme. 5,8-Dimethylspermine caused a marked decrease in the activity of S-adenosylmethionine decarboxylase (AdoMetDC). This effect was not obtained with 1,4-dimethylputrescine, indicating that spermine, but not putrescine, exerts a negative control of AdoMetDC. Treatment with 1,4-dimethylputrescine caused extensive depletion of the cellular putrescine and spermidine content, but accumulation of spermine. 5,8-Dimethylspermine treatment, on the other hand, effectively depleted the spermine content and had less effect on the putrescine and spermidine content, at least initially. Nevertheless, the total polyamine content was more extensively reduced by treatment with 5,8-dimethylspermine than with 1,4-dimethylputrescine. Accordingly, only 5,8-dimethylspermine treatment exerted a significant inhibitory effect on Ehrlich ascites tumor cell growth.

背景与目标： ：鸟氨酸脱羧酶（ODC）受多胺的反馈调节。因此，向细胞中加入腐胺，亚精胺或亚精胺可抑制ODC mRNA的翻译。腐胺和亚精胺很容易转化成亚精胺。因此，可以想象，在补充了腐胺和精胺的细胞中观察到的ODC合成的抑制反而是亚精胺的作用。为了检验这种可能性，我们使用了腐胺和精胺的两个类似物，即1,4-二甲基腐胺和5,8-二甲基精胺，它们不能转化为亚精胺。发现这两种类似物都抑制[35S]蛋氨酸掺入ODC蛋白的程度大致相同，这表明腐胺和精胺对细胞中ODC mRNA翻译具有负反馈控制作用。除了抑制ODC合成外，还发现两种类似物均可增加酶的周转率。 5,8-二甲基精胺导致S-腺苷甲硫氨酸脱羧酶（AdoMetDC）的活性显着下降。 1,4-二甲基酪氨酸没有获得这种效果，表明精胺而不是腐胺发挥了AdoMetDC的阴性对照作用。用1，4-二甲基酪胺酸处理引起细胞中的腐胺和亚精胺含量的大量消耗，但是精胺的积累。另一方面，至少在最初，5，8-二甲基亚精胺处理有效地耗尽了亚精胺含量，并且对腐胺和亚精胺含量的影响较小。然而，通过用5，8-二甲基精胺处理的总多胺含量比用1，4-二甲基腐胺更广泛地降低。因此，仅5，8-二甲基精胺处理对艾氏腹水肿瘤细胞的生长具有显着的抑制作用。

BACKGROUND & AIMS: We have previously suggested the involvement of a Ca(2+)-phosphatidylinositol 4,5-bisphosphate (PIP2) complex in the phospholipid transmembrane redistribution triggered by cytosolic Ca2+ in erythrocytes. Indeed, the lipid scrambling was induced by extracellular Ca2+ in erythrocytes loaded with PIP2 and was abolished in inside-out vesicles prepared from PIP2-depleted erythrocytes (Sulpice, J.C., Zachowski, A., Devaux, P.F., & Giraud, F. (1994) J. Biol. Chem. 269, 6347-6354). Here, we show that Ca2+ triggers a partial redistribution of spin-labeled phospholipids in protein-free large unilamellar vesicles (LUVs), only when they contain PIP2. Spermine, a polyamine known to interact with PIP2 and reported to inhibit lipid scrambling in resealed ghosts, was found to inhibit also the Ca(2+)-induced scrambling in LUVs and in PIP2-loaded erythrocytes, presumably by interacting with PIP2 and preventing the formation of Ca(2+)-PIP2 complexes. A similar mechanism can account for spermine inhibition in natural membranes, confirming the role of PIP2 in the scrambling process without excluding the participation of proteins. In erythrocytes, activation of the phosphoinositide phospholipase C (PLC) or a 20 h ATP depletion, which both led to a reduction in the PIP2 content by 40-60%, did not affect Ca(2+)-induced phospholipid scrambling. In contrast, longer ATP depletion, resulting in a 80% reduction in the PIP2 content, did induce a significant decrease in lipid scrambling, suggesting that only the PIP2 pool resistant to the PLC was involved. Spermine was able to inhibit hydrolysis of this pool by an exogenous PLA2. It is thus likely that spermine antagonized the Ca(2+)-induced scrambling in resealed ghosts by interacting with the PLC-resistant pool of PIP2.

背景与目标： 我们以前曾建议参与Ca（2）-磷脂酰肌醇4,5-二磷酸（PIP2）复合物中的红细胞中细胞质Ca2触发的磷脂跨膜再分布。实际上，脂质扰动是由装载PIP2的红细胞中的细胞外Ca2诱导的，并在由PIP2耗尽的红细胞制备的由内而外的囊泡中被消除（Sulpice，JC，Zachowski，A.，Devaux，PF，＆Giraud，F.（1994年）。 J.Biol.Chem.269，6347-6354）。在这里，我们表明，仅当Ca2包含PIP2时，它才会触发无蛋白的大单层囊泡（LUVs）中自旋标记的磷脂的部分重新分布。精胺，一种已知与PIP2相互作用的多胺，据报道可抑制脂质在重新密封的幽灵中乱码，还可以抑制Ca（2）诱导的乱码在LUV和PIP2加载的红细胞中，大概是通过与PIP2交互作用并防止形成Ca（2）-PIP2配合物。类似的机制可以解释天然膜中精胺的抑制作用，从而在不排除蛋白质参与的情况下确认了PIP2在加扰过程中的作用。在红细胞中，磷酸肌醇磷脂酶C（PLC）的激活或20 h ATP的消耗都导致PIP2含量降低40-60％，但不影响Ca（2）诱导的磷脂加扰。相反，更长的ATP消耗会导致PIP2含量降低80％，确实会导致脂质扰乱现象明显减少，这表明仅涉及对PLC有抗性的PIP2库。精胺能够抑制外源PLA2水解该库。因此，通过与PLC的PIP2耐药性池相互作用，精胺有可能拮抗Ca（2）诱导的重封幽灵中的争夺。

BACKGROUND & AIMS: :The involvement of spinal release of histamine on nociceptive behaviors induced by spermine was examined in mice. Intrathecal spermine produced dose-dependent nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by spermine at 0.02 amol and 10 pmol were markedly suppressed by i.t. pretreatment with antiserum against histamine and were abolished in histidine decarboxylase-deficient mice. In histamine H1 receptor-deficient mice, the nociceptive behaviors induced by spermine were completely abolished after treatment with 0.02 amol of spermine and significantly suppressed after treatment with 10 pmol of spermine. The i.t. pretreatment with takykinin NK1 receptor antagonists eliminated the nociceptive behaviors induced by 0.02 amol of spermine, but did not affect the nociceptive behaviors induced by 10 pmol of spermine. On the other hand, the nociceptive behaviors induced by spermine at both 0.02 amol and 10 pmol were suppressed by i.t. pretreatment with antagonists for the NMDA receptor polyamine-binding site. The present results suggest that the nociceptive behaviors induced by i.t. administration of spermine are mediated through the spinal release of histamine and are elicited via activation of NMDA receptors.

背景与目标： ：在小鼠中检查了组胺的脊柱释放与精胺诱导的伤害感受行为的关系。鞘内精胺产生剂量依赖性的伤害行为，包括抓挠，咬和舔。 i.t.显着抑制了精胺在0.02 amol和10 pmol下诱导的伤害感受行为。用抗组胺的抗血清预处理，在组氨酸脱羧酶缺陷型小鼠中被取消。在组胺H1受体缺陷型小鼠中，由精胺诱导的伤害感受行为在用0.02 amol精胺处理后被完全消除，而在用10 pmol精胺处理后被显着抑制。 i.t.速激肽NK1受体拮抗剂的预处理消除了0.02 amol精胺诱导的伤害行为，但不影响10 pmol精胺诱导的伤害行为。另一方面，通过i.t抑制了精胺在0.02amol和10pmol下诱导的伤害感受行为。 NMDA受体多胺结合位点的拮抗剂预处理。目前的结果表明，由i.t.引起的伤害性行为。精胺的给药通过组胺的脊柱释放来介导，并通过NMDA受体的激活而引起。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Polyamines have fundamental roles in brain homeostasis as key modulators of cellular excitability. Several studies have suggested alterations in polyamine metabolism in stress related disorders, suicide, depression, and neurodegeneration, making the pharmacological modulation of polyamines a highly appealing therapeutic strategy. Polyamines are small aliphatic molecules that can modulate cationic channels involved in neuronal excitability. Previous indirect evidence has suggested that polyamines can modulate anionic GABAA receptors (GABAARs), which mediate inhibitory signaling and provide a direct route to reduce hyperexcitability. Here, we attempted to characterize the effect that spermine, the polyamine with the strongest reported effect on GABAARs, has on human postmortem native GABAARs. We microtransplanted human synaptic membranes from the dorsolateral prefrontal cortex of four cases with no history of mental or neurological disorders, and directly recorded spermine effects on ionic GABAARs responses on microtransplanted oocytes. We show that in human synapses, inhibition of GABAARs by spermine was better explained by alkalization of the extracellular solution. Additionally, spermine had no effect on the potentiation of GABA-currents by diazepam, indicating that even if diazepam binding is enhanced by spermine, it does not translate to changes in functional activity. Our results clearly demonstrate that while extracellular spermine does not have direct effects on human native synaptic GABAARs, spermine-mediated shifts of pH inhibit GABAARs. Potential spermine-mediated increase of pH in synapses in vivo may therefore participate in increased neuronal activity observed during physiological and pathological states, and during metabolic alterations that increase the release of spermine to the extracellular milieu.

背景与目标： ：多胺作为细胞兴奋性的关键调节剂，在脑稳态中具有基本作用。多项研究表明，与应激有关的疾病，自杀，抑郁和神经退行性疾病中多胺代谢的改变，使多胺的药理学调节成为极具吸引力的治疗策略。多胺是小的脂肪族分子，可以调节神经元兴奋性所涉及的阳离子通道。先前的间接证据表明，多胺可调节阴离子性GABAA受体（GABAARs），介导抑制性信号传导并提供降低过度兴奋性的直接途径。在这里，我们试图表征精胺（对GABAARs报道作用最强的多胺）对人类尸体天然GABAARs的影响。我们从4例无精神或神经疾病病史的背外侧前额叶皮层微移植了人类突触膜，并直接记录了精胺对微移植卵母细胞离子GABAARs反应的影响。我们显示，在人类突触中，精胺对GABAAR的抑制作用可以通过细胞外溶液的碱化得到更好的解释。另外，精胺对地西epa对GABA电流的增强没有影响，表明即使精胺增强了地西epa的结合，它也不会转化为功能活性的改变。我们的结果清楚地表明，虽然细胞外精胺对人类天然突触GABAAR没有直接影响，但精胺介导的pH改变会抑制GABAAR。因此，潜在的精胺介导的体内突触中pH值的增加可能参与了生理和病理状态以及代谢改变（增加了精胺向细胞外环境的释放）过程中观察到的神经元活性的增加。

BACKGROUND & AIMS: :We compared the transcriptional activities of the circular and linear forms of short (4kbp) and giant (106kbp) DNA molecules in the presence of a polyamine, spermine (4+). With an increase in the spermine concentration, transcriptional activity was enhanced, followed by an inhibitory effect, and complete inhibition was observed in the sole case of long, linear templates. A difference between the transcriptional properties of circular and linear conformations is found for giant DNA molecules. These results are discussed in relation to DNA conformational transitions.

背景与目标： ：我们比较了在存在多胺精胺的情况下，短（4kbp）和巨大（106kbp）DNA分子的环状和线性形式的转录活性。随着精胺浓度的增加，转录活性增强，随后产生抑制作用，在长而线性模板的唯一情况下，观察到完全抑制。发现巨型DNA分子的环状和线性构象的转录特性之间存在差异。讨论了有关DNA构象转变的这些结果。

BACKGROUND & AIMS: :The presence of polyamines in living cells is crucial for survival. Due to their high net charge at physiological pH, polyamines effectively charge neutralize the phosphodiester backbone of DNA in an interaction that also may protect the DNA from external damage. We here present a study illustrating the influence of spermidine and spermine on the platination reactions of the model oligonucleotides d(T(6)GT(6)), d(T(12)GT(12)), and d(T(24)GT(24)), and the pUC18 DNA plasmid. The aquated forms of the anticancer active compounds cisplatin (cis-[Pt(NH(3))(2)Cl(2)]) and the major Pt(II) metabolite of JM216 (cis-[PtCl(2)(NH(3))(c-C(6)H(11)NH(2))], JM118) were used as platination reagents. The study shows that the kinetics for formation of the coordinative Pt-DNA adduct are strongly influenced by the presence of sub-millimolar polyamine concentrations. At polyamine concentrations in the muM-range, the reactions remain salt-dependent. In contrast, platination of pUC18 is effectively prevented at mM concentrations of both spermidine and spermine with the latter as the more potent inhibitor. The results suggest that variations of intracellular polyamine concentrations may have a profound influence on the efficacy by which cationically charged reagents interfere with DNA function in vivo by modulation of the preassociation conditions.

背景与目标： ：活细胞中多胺的存在对生存至关重要。由于它们在生理pH值下具有高净电荷，因此多胺在相互作用中有效地中和了DNA的磷酸二酯主链，这也可以保护DNA免受外部损害。我们在这里进行了一项研究，阐明了亚精胺和亚精胺对模型寡核苷酸d（T（6）GT（6）），d（T（12）GT（12））和d（T（24）的电镀反应的影响）GT（24））和pUC18 DNA质粒。 JM216的抗癌活性化合物顺铂（cis- [Pt（NH（3））（2）Cl（2）]）和主要Pt（II）代谢产物的水合形式（cis- [PtCl（2）（NH（ 3））（cC（6）H（11）NH（2）），JM118）用作电镀试剂。研究表明，亚毫摩尔多胺浓度的存在强烈影响形成配位的Pt-DNA加合物的动力学。在muM范围内的多胺浓度下，反应仍然依赖于盐。相反，在mM浓度的亚精胺和精胺中，有效抑制pUC18的电镀反应，后者是更有效的抑制剂。结果表明，细胞内多胺浓度的变化可能会对阳离子带电试剂通过调节预缔合条件在体内干扰DNA功能的功效产生深远影响。