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。

BACKGROUND & AIMS: :Harold, F. M. (National Jewish Hospital, Denver, Colo.). Stabilization of Streptococcus faecalis protoplasts by spermine. J. Bacteriol. 88:1416-1420. 1964.-Lysis of protoplasts of Streptococcus faecalis subjected to osmotic shock was prevented by the presence of 10(-3)m spermine and other divalent cations. Protein and nucleic acids were largely retained, but compounds of low molecular weight were discharged into the medium and the capacity for glycolysis was lost. Under these conditions, spermine was bound to the protoplasts. It could not be removed by washing with water or nonelectrolytes, but was displaced by salts, polyanions, and polycations. Removal of the spermine restored the osmotic fragility of the protoplasts, which could once again be protected from lysis by impermeant solutes. Protoplasts were also stabilized, in the absence of osmotic shock, by prolonged incubation with cations in 0.5 m sucrose. By either procedure, the protoplasts became resistant not only to osmotic lysis but also to sonic oscillation. It is concluded that the stabilization of protoplasts resulted from ionic binding of the cation to acidic sites on the external surface of the plasma membrane. This conferred upon the membrane additional mechanical strength, perhaps by the cross-linking of subunits, but did not alter its permeability to extracellular solutes.

背景与目标： ：Harold，F. M.（科罗拉多州丹佛国家犹太医院）。精胺稳定粪便链球菌的原生质体。 J.细菌。 88：1416-1420。 1964.-由于10（-3）m精胺和其他二价阳离子的存在，阻止了渗透性休克的粪链球菌的原生质体裂解。蛋白质和核酸大部分保留，但低分子量化合物排入培养基，糖酵解能力丧失。在这些条件下，精胺与原生质体结合。不能通过用水或非电解质洗涤将其除去，而是被盐，聚阴离子和聚阳离子取代。去除精胺可恢复原生质体的渗透性脆性，可以再次通过渗透性溶质保护其免受溶解。在没有渗透性休克的情况下，通过与阳离子在0.5 m的蔗糖中长时间孵育，原生质体也得以稳定。通过这两种方法，原生质体不仅对渗透裂解具有抵抗力，而且对声波振荡也具有抵抗力。结论是，原生质体的稳定是由于阳离子与质膜外表面酸性位点的离子结合所致。这可能通过亚基的交联赋予了膜额外的机械强度，但并未改变其对细胞外溶质的渗透性。

BACKGROUND & AIMS: :It has been reported in the literature that a leukemic cell may be (or become) resistant to anti-cancer treatment because many mechanisms, such as efflux membrane pump (multi-drug resistance, MDR-P170), intracellular transport (LRP, MRP), or different detoxification systems (glutathione transferases, methallothioneines) may be implicated. Topoisomerase II alpha (TopoII) are also reported as responsible for resistance since their main action is to repair DNA breakage. Polyamines are described as having a protective DNA action by stabilizing the double stranded DNA helix. For these reasons we investigated 65 children with acute lymphoblastic leukemia using an immunocytochemical method to elucidate the potential role of Topoisomerase and polyamines in drug resistance. Most children (60/65) were treated with the French (acute lymphoblastic leukemia, ALL) protocol (FRALLE-93) in which B and C arms include (at least) VP16. Children with cytoplasmic TopoII positivity (18 cases) were more resistant since their overall survival was 34 months compared to more than 110 months for negative cases ( P = 0.0003). Polyamines may be associated with drug resistance since the overall survivals were 51 months and 92 months for positive and negative patients, respectively, but the P-value is only 0.13. We conclude that Topoisomerase and polyamines must be tested at diagnosis as new possible markers for chemo-resistance. Larger series are needed to confirm these preliminary results and to verify if the use of anti epipodophillotoxin agents (as it is the case for FRALLE B or C) should be excluded for positive cases.

背景与目标： ：有文献报道白血病细胞可能（或变得）对抗癌治疗有抗性，因为许多机制，例如外排膜泵（多药抗性，MDR-P170），细胞内转运（LRP，MRP） ），也可能涉及其他排毒系统（谷胱甘肽转移酶，甲硫醚）。据报道拓扑异构酶IIα（TopoII）引起耐药性，因为它们的主要作用是修复DNA断裂。多胺被描述为通过稳定双链DNA螺旋具有保护性DNA作用。由于这些原因，我们使用免疫细胞化学方法调查了65例急性淋巴细胞白血病儿童，以阐明拓扑异构酶和多胺在耐药中的潜在作用。大多数儿童（60/65岁）均接受了法国（急性淋巴细胞白血病，ALL）治疗方案（FRALLE-93）治疗，其中B和C臂均包括（至少）VP16。具有胞质TopoII阳性的儿童（18例）具有更大的抵抗力，因为它们的总生存期为34个月，而阴性病例则超过110个月（P = 0.0003）。多胺可能与耐药性有关，因为阳性和阴性患者的总生存期分别为51个月和92个月，但P值仅为0.13。我们得出结论，拓扑异构酶和多胺必须在诊断时进行测试，作为抗化学性的新可能标记。需要更大的系列数来确认这些初步结果，并验证对于阳性病例是否应排除使用抗表皮脂蛋白毒素药物（如FRALLE B或C的情况）。

BACKGROUND & AIMS: To evaluate the requirement of bovine adrenal chromaffin cells for inositol phospholipids in secretion, the effects of neomycin and spermine on secretion and phosphoinositide metabolism were compared. Spermine and neomycin had virtually identical effects on secretion and phosphoinositide levels. Both polyamines 1) partially maintained secretion when added to permeabilized cells in the absence of ATP, 2) had no effect when added to cells in the presence of ATP and 3) inhibited secretion when present with the Ca2+ stimulus. In the absence of ATP the enhancements to secretion due to incubation with either polyamine were associated with sustained levels of the polyphosphoinositides. The ability of spermine and neomycin to maintain secretion and the polyphosphoinositides in the absence of ATP supports the hypothesis that the maintenance of the polyphosphoinositides is necessary for secretion. Neomycin was found to inhibit Ca2+ stimulated production of both inositol bis- and tris-phosphates while spermine was found to selectively inhibit inositol bis-phosphate production and had no effect on Ca(2+)-stimulated inositol tris-phosphate production in permeabilized cells.

背景与目标： 为了评估牛肾上腺嗜铬细胞对分泌的肌醇磷脂的需求，比较了新霉素和精胺对分泌和磷酸肌醇代谢的影响。精胺和新霉素对分泌和磷酸肌醇水平具有几乎相同的作用。两种多胺1）在不存在ATP的情况下添加到通透性细胞中时部分维持分泌，2）在不存在ATP的情况下添加到细胞中则无作用，3）当存在Ca2刺激时抑制分泌。在不存在ATP的情况下，由于与任何一种多胺一起孵育而导致的分泌增强与持续水平的多磷酸肌醇有关。在没有ATP的情况下，精胺和新霉素维持分泌的能力以及多磷酸肌醇的能力支持了以下假设：维持多磷酸肌醇对于分泌是必需的。发现新霉素可以抑制Ca2刺激的肌醇双磷酸和三磷酸酯的生产，而精胺被发现可以选择性地抑制肌醇双磷酸酯的生产，并且对透化细胞中Ca（2）刺激的肌醇三磷酸的生产没有影响。 br>

BACKGROUND & AIMS: Developmental change in the potentiation of N-methyl-D-aspartate (NMDA) responses by spermine was investigated on the ventromedial hypothalamic neurones acutely dissociated from the rats aged between 5 and 21 days, using a nystatin perforated patch clamp recording in a whole cell mode. Spermine potentiated the NMDA response in a concentration dependent manner between 10(-5) M and 10(-5) M at all ages examined. This potentiation decreased significantly with age. On the other hand, spermine did not affect the kainate and AMPA responses at any age. This developmental change of the modulation of NMDA responses might influence to or be influenced by the behavioural and neuronal changes related to the VMH in the early postnatal life.

背景与目标： 在全细胞模式下，使用制霉菌素穿孔的膜片钳记录了从5到21天的大鼠急性解离的腹膜下丘脑神经元，研究了精胺对N-甲基-D-天冬氨酸（NMDA）应答的增强作用的发育变化。 。在所有检查的年龄中，精胺都以浓度依赖性的方式增强了NMDA的响应，浓度介于10（-5）M和10（-5）M之间。随着年龄的增长，这种增强作用显着降低。另一方面，精胺在任何年龄均不影响红藻氨酸和AMPA反应。 NMDA反应调节的这种发展变化可能会影响或受到产后早期与VMH相关的行为和神经元变化的影响。

BACKGROUND & AIMS: Effects of antizyme on polyamine transport and spermine restoration of the growth of polyamine-deficient cells were examined by using mouse FM3A cells transfected with pMAMneoZ1 possessing rat antizyme cDNA under the control of glucocorticoid-inducible promoter. Treatments of the transfected cells with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and dexamethasone, an inducer of antizyme, both caused a decrease in ODC activity and polyamine contents and inhibition of cell growth. However, spermine uptake of the transfected cells was repressed by dexamethasone but stimulated by DFMO. The decrease in the rate of spermine uptake in dexamethasone-treated cells was attributed to an increase in Km value and a slight decrease in Vmax value. Accordingly, restoration of cell growth by spermine was less effective in dexamethasone-treated cells than DFMO-treated cells. These results clearly indicate that antizyme has dual functionsone for ODC degradation and the other for negative regulation of polyamine transport.

背景与目标： 通过在糖皮质激素诱导型启动子的控制下，使用转染了具有大鼠酶cDNA的pMAMneoZ1的小鼠FM3A细胞，研究了酶对多胺转运和精胺还原多胺缺陷细胞生长的影响。用鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸（DFMO）和抗酶诱导剂地塞米松处理转染的细胞，都会导致ODC活性和多胺含量降低，并抑制细胞生长。然而，地塞米松抑制了转染细胞对精胺的吸收，但DFMO对其进行了刺激。地塞米松处理的细胞中精胺摄取速率的降低归因于Km值的增加和Vmax值的轻微降低。因此，在用地塞米松处理的细胞中，用精胺恢复细胞生长的效果不如用DFMO处理的细胞。这些结果清楚地表明，抗酶具有双重功能，一个用于ODC降解，另一个用于负调节多胺转运。

BACKGROUND & AIMS: :dcAdoMet (decarboxylated S-adenosylmethionine) is an essential intermediate in the synthesis of polyamines. Its content is normally very low, amounting to less than 5% of that of S-adenosylmethionine itself. It was found that in mice lacking spermine synthase there was a large increase in dcAdoMet and that overexpression of spermine synthase reduced the amount of this nucleoside. There was also an increase in dcAdoMet in cells derived from patients with Snyder-Robinson syndrome, a rare X-linked recessive human disease caused by SMS gene mutations that greatly reduce the content of spermine synthase. These results suggest that there is an inverse relationship between the amount of spermine synthase protein and the content of dcAdoMet and raise the possibility that some of the abnormalities seen in mammals deficient in spermine synthase might be due to changes in dcAdoMet pools.

背景与目标： ：dcAdoMet（脱羧S-腺苷甲硫氨酸）是多胺合成中必不可少的中间体。它的含量通常很低，不到S-腺苷甲硫氨酸本身的5％。发现在缺乏精胺合酶的小鼠中，dcAdoMet大量增加，并且精胺合酶的过表达减少了该核苷的量。患有Snyder-Robinson综合征的患者的细胞中dcAdoMet也有所增加，Snyder-Robinson综合征是一种罕见的X连锁隐性人类疾病，由SMS基因突变引起，大大降低了精胺合成酶的含量。这些结果表明，精胺合酶蛋白的量与dcAdoMet的含量之间存在反比关系，并增加了在精胺合酶不足的哺乳动物中发现的某些异常可能是由于dcAdoMet库变化引起的可能性。