不同氨基酸受体拮抗剂对缺血纹体CCK—8释放的影响

目的：研究不同兴奋性氨基酸受体拮抗剂（ＭＫ８０１，Ｓｐｅｒｍｉｎｅ，ＤＮＱＸ）对大鼠脑缺血时纹体缩胆囊肽－８（ＣＣＫ－８）释放的影响。方法：用微透析和ＲＩＡ法测定半球缺血时纹体ＣＣＫ－８的释放。结果：脑缺血时纹体ＣＣＫ－８释放明显增高，缺血前分别给予三种拮抗剂，都明显地降低缺血时纹体ＣＣＫ－８的不正常释放。结论：表明脑缺血时的ＣＣＫ－８和兴奋性氨基酸（ＥＡＡ）之间有协同的相互作用，抑制ＣＣＫ－８释放增高，可能是兴奋性氨基酸受体拮抗剂保护缺血大脑的机制之一。     

The Relationship Between the Immunosuppressive and Cytotoxic Effects of Human Seminal Plasma

ABSTRACT: This report describes the cytotoxic properties of human seminal plasma and demonstrates that the inhibition of response to mitogens shown by murine lymphocytes in the presence of whole human seminal plasma can be attributed largely to an effect of seminal components on lymphocyte viability. It is hypothesised that the cytotoxic effect of seminal plasma arises as a result of the oxidation of spermine in seminal plasma by an amine oxidase enzyme present in fetal calf serum. In support of this hypothesis, it was found that seminal plasma cytotoxicity is serum dependent and is inhibited in the presence of the amine oxidase inhibitor hydroxylamine     

Role of Spermine in the Cytotoxic Effects of Seminal Plasma

ABSTRACT: This report further characterizes the cytotoxic properties of seminal plasma and provides evidence for a role of spermine oxidation in the generation of seminal plasma cytotoxicity. Addition of spermine to lymphocyte cultures was found to result in a cytotoxic effect similar to that observed upon addition of seminal plasma. Furthermore, although seminal plasma is not cytotoxic in serum-free medium, addition of monoamine oxidase was sufficient to result in the generation of seminal plasma-associated cytotoxicity. Analysis of 73 individual seminal plasma samples indicated that all were cytotoxic, suggesting that this is an intrinsic property of seminal plasma. These results support a mechanism for seminal plasma cytotoxicity in which oxidation of spermine in seminal plasma by the amine oxidase of fetal calf serum results in generation of a cytotoxic product. It is hypothesized that this product plays a significant role in the phenomenon of seminal plasma immunosuppression. The general application of this principle to other fluids and tissues is discussed.     

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.     

Aerosol delivery of spermine-based poly(amino ester)/Akt1 shRNA complexes for lung cancer gene therapy

Polyethylenimine (PEI) has been commonly used as a cationic polymeric gene carrier due to high transfection efficiency, however, its cytotoxicity has hindered the practical application. In this study, we report the development of poly(amino ester) (PAE) based on glycerol propoxylate triacrylate (GPT) and spermine (SPE) as an alternative gene carrier for lung cancer therapy. GPT-SPE copolymer was prepared by Michael addition reaction between GPT and SPE, and the efficacy was evaluated using shAkt1 as a model therapeutic gene. The molecular weight and composition were characterized using gel permeability chromatography (GPC) and ¹H-nuclear magnetic resonance (¹H-NMR), respectively. The GPT-SPE could effectively condense DNA with about 163 nm size and protect the DNA from nucleases. GPT-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo. Furthermore, aerosol delivery of GPT-SPE/Akt1 shRNA complexes significantly suppressed lung tumorigenesis in K-ras^LA1 lung cancer model mice. These results suggest that GPT-SPE can be used in shRNA-based lung cancer gene therapy.     

Spermine does not compete with ω-conotoxin GVIA in the stratum radiatum of the hippocampal slice

The effect of spermine (Spm) and of ω-conotoxin GVIA (CTX) on the population excitatory postsynaptic potentials (pEPSP) in stratum radiatum of the CA1 area were compared. CTX decreased irreversibly the initial slope of pEPSP by 57%. Spm produced a maximum inhibition of 85% with an apparent dissociation constant of 0.85 mM and a maximum Hill coefficient larger than 3. The effect of Spm was mostly reversible. Preincubation with Spm did not protect the slice from the irreversible effect of CTX suggesting that they interact with different sites. Since CTX and Spm inhibited pEPSPs with very different affinities and reversibilities a kinetic model was developed to compare their effects. This model relates the inhibitors' binding to presynaptic voltage-activated Ca²⁺ channels (VACC) with inhibition of pEPSP. The model suggest that: all CTX and Spm effects can be explained by inhibition of VACC. Spm and CTX do not compete for the same site. CTX inhibits 20% (N-type) and Spm 40% of channels (probably the Q-type). More than three Spm molecules bind per one channel molecule, while one CTX is sufficient to inhibit channel function. The model also illustrates that the inhibitor concentration–pEPSP inhibition curves display a Hill coefficient similar to that for inhibitor binding.     

Spermine is neuroprotective against anoxia and N-methyl--aspartate in hippocampal slices

Polyamines were implicated as either neurotoxic or neuroprotective in several models of stroke. Spermine augments the excitotoxicity mediated by the N-methyl--aspartate (NMDA) receptor because this receptor is activated at micromolar spermine concentrations. However, at higher concentrations, spermine could be neuroprotective because it blocks the NMDA receptor and voltage-activated Ca²⁺ channels. In this work, acute hippocampal slices were exposed to 1 mM spermine and either 10 min of anoxia or 0.5 mM NMDA. The percent recovery of population spikes was the measure of neuroprotection. One millimolar spermine was robustly neuroprotective; however, 0.1 mM spermine and 1 mM putrescine were not. The neuroprotective concentration of spermine was higher than the physiological concentration of free spermine. However, during an excitotoxic episode, extracellular Ca²⁺ is decreased, enabling the inhibitory activity of lower spermine concentration. In addition, several noxious stimuli trigger the release of intracellular spermine and could raise local levels of spermine. Therefore, it is possible that spermine has a neuroprotective role in vivo.     

Regional differences in the activation of synaptosomal mitochondrial Ca uptake by spermine in rat brain

Several properties of Ca²⁺ uptake by isolated synaptosomal mitochondria were characterized by using a repetitive Ca²⁺ loading technique. Synaptosomal mitochondria maintained extramitochondrial Ca²⁺ concentration at submicromolar levels when challenged with successive additions of small amounts of Ca²⁺. Ca²⁺ uptake under these conditions was markedly stimulated by the presence of spermine, a polyamine found in high concentrations in brain. Moreover, mitochondria isolated from telencephalic areas of rat brain were activated to a greater extent by spermine than were mitochondria from non-telencephalic brain regions. The present results support the idea that brain mitochondria could play a significant role in limiting the intraneuronal rise in Ca²⁺ that follows stimulation or injury. In addition, telencephalic mitochondria exhibit more flexibility in the regulation of Ca²⁺ uptake than do mitochondria from phylogenetically older non-telencephalic brain regions and this could be related to differences in Ca²⁺ influx mechanisms in these brain regions.     

A novel macrocyclic spermine alkaloid from Incarvillea sinensis

A novel macrocyclic spermine alkaloid incasine C' (1), along with a known compound incasine C (2), were isolated from the whole plants of Incarvillea sinensis, and their structures were elucidated on the basis of chemical and spectroscopic evidence.     

Regulating T-cell differentiation through the polyamine spermidine

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