• International Journal of Oral Biology
• /
• 제38권4호
• /
• pp.155-160
• /
• 2013

The major issue in the development of nucleic acid based therapeutics is the inefficient delivery of these agents into cells. We prepared cholesterol conjugated spermine and evaluated its usefulness as a delivery modality for antisense oligonucleotides in HeLa-Luc cells. A 2'-O-methyl antisense oligonucleotide sequence, designed to correct splicing at an aberrant intron inserted into a normal luciferase reporter gene, was used for complex formation with cholesterol conjugated spermine. Effective delivery of this antisense agent into nucleus would results in the expression of a luciferasereporter gene product. The cholesterol-spermine formed stable complexes with the antisense oligonucleotide and showed modest delivery activity. Furthermore, this delivery activity was maintained even in the presence of serum proteins, mimicking in vivo conditions. Cholesterol-spermine thus has potential as a delivery system for antisense oligonucleotides into cells.

• Journal of Plant Biology
• /
• 제37권4호
• /
• pp.397-402
• /
• 1994

Possible roles of polyamines in the inhibition of cell elongation in Ranunculus petioles were investigated. Exogenously apoplied polyamines greatly inhibited the auxin-induced petiole growth, while treatment of the tissue with $\alpha$-difluoromethylarginine, the inhibitor of putrescine biosynthesis, further enhanced the growth in the presence of IAA. Inhibitory effect of spermine can also be apparent for fusicoccin-induced elongation, but not for growth induced by a low pH. Spermine also suppressed the ethylene-enhanced growth in the presence of auxin. Using computer-based video digitizer system, the inhibitory effects of spermine on petiole growth were kinetically analyzed. Auxin-induced growth was characterized by an initial and transient growth with a highly elevated rate followed by a steady growth with a slightly reduced rate. Spermine treatment was found to shorten the duration of the initial phase of growth, and to reduce the rates of both the initial and steady growth as well. The latent period for auxin induction was not affected by spermine.

• 약학회지
• /
• 제43권4호
• /
• pp.535-540
• /
• 1999

Glutamate (Glu) receptor-mediated excitoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15-18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4∼5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature enurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced toxicity was potentiated by spermine in a concentration-dependent manner. Again, the spermine-enhanced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in excitotoxicity in immature neurons.

• 대한화학회지
• /
• 제29권3호
• /
• pp.304-310
• /
• 1985

송아지 흉선 nucleohistone의 DNase 1에 對한 susceptibility와 相互作用의 cooperativity에 미치는 spermine의 效果를 nucleostone의 構造變移와 關聯시켜 調査하였다. 이들 data로 부터 nucleohistone은 遊離 DNA와는 對照的으로 spermine에 의하여 monomoclecular condensation을 일으키지 않고 intermolecular aggregation을 이루며 nucleohistone의 DNase 1과의 相互作用 cooperativity가 spermine에 의하여 增加됨을 推理할 수 있다. Nucleohistine의 histone 部分의 cooperativity에 關한 機能的 役割을 究明하기 위하여 histone 部分을 단실化시킨 DNS-nucleohistone을 製造하여 DNase 1 과의 相互作用을 調査하여 보았는바 negative cooperativity로 나타났다. 이로 부터 nucleohistone의 histone部分은 nucleohistone의 cooperativity에 影響을 미치리라고 推理할 수 있다.

• 식물조직배양학회지
• /
• 제21권4호
• /
• pp.207-213
• /
• 1994

Cryclohexylarnine(CHA)에 의한 부정근 억제가 spermidine 과 spermine에 의한 부정근 형성 회복에 미치는 영향을 알아 보고자 대두 자엽 절편을 이용하여 조직내의 polyamine함량을 조사하였다. 부정근 형성 배지에 CHA를 처리한 결과 $10^{-2}$ M CHA 처리시에는 spermidine이나 spermine을 혼합처리함에도 불구하고 부정근이 형성되지 않았다. 또한 2.5 $\times$ $10^{-3}$ M CHA 단독처리시에는 부정근 형성이 억제되었으나, $10^{-4}$ M spermine 혼합처리시에는 부정근 형성능이 회복되었다. Putrescine 함량은 부정근이 형성돠지 않았던 $10^{-2}$ M CHA 단독 처리구 및 $10^{-2}$ M CHA와 $10^{-3}$ M Spermine 혼합처리구에서는 배양 3일 이후 대조구보다 감소하였지만 부정근이 다소 형성되었고, 부정근 회복능이 가장 높았던 2.5 $\times$ $10^{-3}$ M CHA와 $10^{-4}$ M spermine 혼합처리구에서는 대조구보다 높은 함량을 나타내었다. Spermidine 함량은 모든 처리구에서 대조구보다 낮아서 함량이 낮을수록 부정근 형성이 억제되었으며, spermine의 함량은 대조구에 비하여 모든 처리구에서 급격히 증가되어 대조구에 비하여 함량이 높을 수록 부정근 형성이 억제되었다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제31권8호
• /
• pp.1325-1335
• /
• 2018

Objective: This study investigated whether spermine supplementation could regulate cell cycle, apoptosis, and amino acid transporter-related genes expression in the thymus and spleen of early weaned piglets. Methods: Eighty female piglets were randomly distributed to receive adequate nutrients supplemented with spermine (0.4 mmol/kg body weight/24 h) or to be provided with restricted nourishment supplemented with normal saline for 7 h or 3, 6, or 9 d in pairs. Results: Regardless of administration time, spermine supplementation significantly up-regulated cyclin A2 gene expression but down-regulated p21 and cyclin D3 mRNA levels in the thymus and spleen and reduced cyclin E2 gene expression in the thymus of piglets (p<0.05). Irrespective of the treatment period, the reduced Bax and caspase-3 gene expressions and improved Bcl-2 mRNA level were observed in the thymus and spleen of spermine-administrated piglets (p<0.05). Regardless of supplementation time, spermine intake significantly enhanced the expressions of amino acid transporter-related genes (SLC1A1, SLC1A5, SLC7A1, SLC7A7, and SLC15A1) in both thymus and spleen, as well as SLC7A9 in the spleen of piglets (p<0.05). In addition, extended spermine administration also markedly promoted cell proliferation, depressed apoptosis and modulated amino acid transport (p<0.05), and such effects were the greatest during prolonged spermine supplementation (6 d) compared to the other time periods (p<0.05). Conclusion: Spermine supplementation may regulate cell cycle during the G1/S phase, suppress apoptosis and modulate amino acid transport. A period of 6 d of spermine supplementation is required to produce the optimal effects on nutritional implications.

• The Korean Journal of Physiology and Pharmacology
• /
• 제24권1호
• /
• pp.101-110
• /
• 2020

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.

• Journal of Plant Biology
• /
• 제33권4호
• /
• pp.217-223
• /
• 1990

Restriction enzyme inhibiting substance (REIS) extracted from spinach chloroplast and Chlamydomonas seems not to be proteinaceous, because its inhibiting activity was not lost by heat or trypsin treatment. And it seems not to be lipid or polysacchride, because its inhibiting activity was not lost by lipase or $\alpha$-amylase treatment, respectively. In Chlamydomonas, putrescine, spermidine and spermine were present. The amount of putrescine was the smallest and that of spermie was the greatest. But only spermine was contained in REIS and the activity of REIS. It was proportional to the amount of spermine in REIS and it was hindered by Na+ ion. So, the inhibiting activity of REIS seems to be deeply related to spermine contained in REIS. But restriction enzyme inhibiting activity remained to the some extent although salts and spermine were eliminated by dialysis.

• Journal of Microbiology
• /
• 제35권4호
• /
• pp.315-322
• /
• 1997

The effects of a polyamine, spermine, on the differentiation of Naegleria gruberi amebas into flagellates were tested. Addition of spermine at early stages of differentiation (until 40 min after the initiation of differentiation) completely inhibited the differentiation. To understand the inhibition mechanism, we examined the effect of spermine treatment on the transcription and translation of differentiation-specific genes during differentiation. Addition of spermine at early stages did not inhibit the accumulation of two differentiation-specific mRNAs, ${\alpha}$-tubulin and Class I mRNA, significantly, but rather prevented the rapid degradation of the mRNAs in later overall protein synthesis partially and gradually. However, translation of the ${\alpha}$-tubulin mRNA was completely inhibited. These data suggest that the inhibition of differentiation of N. gruberi by spermine treatment did not result from the inhibition of transcription of differentiation-specific genes but from the specific inhibition of translation of the mRNAs during the differentiation.

• 대한화학회지
• /
• 제29권5호
• /
• pp.533-538
• /
• 1985

Spermine에 의하여 誘發되는 凝縮 DNA 構造의 安定化에 있어서 hydrophobic interaction의 重要性을 試驗하기 위하여 spermine-DNA 複合體의 異例的 吸光度-溫度 樣相에 미치는 urea의 效果를 調査하였다. 그 結果 異例的 吸光度-溫度 樣相의 downward peak(trough) 領域에 이르는 相變移에 對한 cooperativity, enthalpy, midpoint의 값들이 Tm 領域의 값들 보다 urea에 敏感한 影響을 받았으며, urea의 濃度 增加에 따라 downward peak가 점차 사라졌다. 이 data는 異例的 吸光度-溫度 樣相을 構成하는 downward peak가 spermine에 의하여 誘發되는 hydrophobic interaction에 의한 凝縮된 tertiary structure의 形成을 나타내고 있다고 불 수 있다.