• Title/Summary/Keyword: polyamine inhibitor

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Correlations Between Polyamine and Adventitious Shoot Regeneration from Populus Leaf Segments (포플라 잎절편의 부정아 분화와 Polyamine 함량의 연관성)

  • 김성호
    • Journal of Plant Biology
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    • v.36 no.1
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    • pp.1-8
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    • 1993
  • Polyamine contents and the activities of their main biosynthetic enzymes, arginine decarboxylase (ADC) and ornithine decarboxylase(ODC), were investigated in Populus leaf segments during adventitious shoot regeneration with the addition of 1 millimolar polyamine synthesis inhibitors. From the study of polyamine synthesis inhibitors, ODC was found to be the principal route of polyamine biosynthesis in adventitious shoot regeneration of Populus leaf segments. The ADC inhibitor difluoromethyl arginine(DFMA) and ODC inhibitor difluoromethyl ornithine(DFMO) strongly reduced the putrescine content. On the contarary, DCHA, an inhibitor of spermidine synthase, increased it. Spermidine content was decreased with the treatment of each polyamine synthesis inhibitor, but the inhibitory effect of DCHA was stronger than any other polyamine inhibitor. The decreased polyamine level by polyamine synthesis inhibitors was restored with the exogenously applied polyamine. Comparing the polyamine contents with the adventitious shoot regeneration rate, were observed a close correlation between spermidine content and adventitious shoot regeneration of Populus leaf segments.

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Changes in Polyamine Level and Chloroplast DNA Methylation in Chlamydomonas reinhardtii (Chlamydomonas의 Polyamine 함량변화와 엽록체 DNA Methylation)

  • 이순희
    • Journal of Plant Biology
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    • v.37 no.1
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    • pp.101-109
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    • 1994
  • Relationship between polyamine level and DNA methylation in the absence or presence of MGBG(l mM), which is an enzyme-activated reversible inhibitor of SAMDC, has been investigated during gametogenesis of Chlamydomonas. In the absence of MGBG, polyamine levels decreased in Chlamydomonas 137C(+) and 137C(-) during gametogenesis. And polyamine level of 137C(+) was 2-5 times as much as that of 137C(-) and showed a significant decrease unlike that of 137C(-). In vitro, MGBG inhibited ctDNA methylation of 137C(+) by 20-30% but did not inhibited that of 137C(-). Also, MGBG inhibited DNA methylase by 60% in vitro. The results obtained in the present work suggest the possibility that the changes of polyamine level may be associated with ctDNA methylation during gametogenesis of Chlamydomonas.omonas.

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Effects of Polyamine Inhibitors and Polyamines on the Adventitious Root Formation from Soybean Cotyledons (Polyamine 합성 저해제와 Polyamine이 대두 자엽 부정근의 형성에 미치는 영향)

  • 한태진;이동원;이순희
    • Korean Journal of Plant Tissue Culture
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    • v.21 no.2
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    • pp.105-110
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    • 1994
  • In order to study on the effect of polyamine inhibitors and polyamines on adventitious root formation the correlation between adventitious root formation and polyamine levels were investigated in cultured soybean (Glycine max L.) cotyledons. Adventitious root formation was inhibited in medium containing 10$^{-4}$ -10/ sup -2/ M polyamine inhibition such as $\alpha$-difluoromethylornithine (DFMO), $\alpha$-difluoromethylarginine (DFMA), cyclohexylammonium sulfate (CHA), dicyclohexyl-amine (DCHA) and methylglyoxal-bis (guanylhydrazone) (MGBG). An inhibitory effects at 10$^{-3}$ M MCBG were much higher than other treatments. Treatment with 10$^{-3}$ M MGBG plus 10$^{-5}$ M spermine led to reversal of the effects of MGBG alone. The polyamine levels were sharply increased in the first few days in each treatnent compared to control. The remarkably increasing polyamine contents were observed in medium supplemented spermine.

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Polyamines in Multi-drug Resistant Cancer Cells (다제 내성 암세포에서의 Polyamine 특성)

  • 권혁영;이종호;이동권
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.265-271
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    • 1997
  • Since the advent of chemotherapy, certain types of cancer have been particularly resistant to chemotherapeutic treatment. One of the most well-studied types of resistance is resistance to multiple struc-turally dissimialr hydrophobic chemotherapeutic agents, or multidrug resistance (MDR). We found that MDR cells (KBV20C, KB7D) being highly resistant to colchicine, etoposide, and vincristine were found to have very low level of putrescine and low level of spermidine than the drug sensitive parental cells (KB) but they had almost same level of spermine as the drug sensitive cells. Although both MDR and drug sensitive cells had almost same rate of polyamine uptake, MDR cells were much more sensitive to an inhibitor of polyamine synthesis, methylglyoxal-bis guanylhydrazone (MGBG), suggesting that MDR cells might be defective in polyamine synthesis. These results also suggest that HGBG can be used for treatment of MDR in vivo.

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Effect of Polyamine Biosynthesis InhibItion on the Microbicidai and Jumoriddal Activities in Mouse Macrophage (생쥐 대식세포의 감염균 치사활성과 종양 치사활성에 미치는 Polyamine 생합성 억제의 영향)

  • 이준백;정노팔
    • The Korean Journal of Zoology
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    • v.34 no.2
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    • pp.173-180
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    • 1991
  • The objective of this experiment was to examine the effect of polyamine depletion by polyamine biosynthesis inhibitors on microbicidal activity and tumoricidal activity in mouse mac-rophages. $\alpha$ -Difluoromethylomithine (DFMO), inhibitor of putrescine and spernidine biosynthesis, treatment in vivo for 6-8 days reduced chemiluminescence levels in thioglycollate-, lipo-polysaccharide (LPS), and BCG-treated mouse macrophages. An DFMO treatment in vitro inhibited production of tumor necrosis factor (TNF), in dose-dependent manner, and tumoricidal activity by macrophages. The effect of polyamine depletion by MO on ThF production and tumoricidal activity could be reversed by the addition of exogenous putrescine. These result indicated that the obserbed effect of DFMO on macrophage activities were mediated through inhibition of polyamines are, must be, required for optimal activities of macrophages.

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Characterization of Putrescine Uptake in Hamster Amelanocytic Melanoma AMEL-3 Cells

  • Garcia-Fernandez, Antonio J.;Rodriguez, Rosa A.;Perez-Pertejo, Yolanda;Balana-Fouce, Rafael
    • Molecules and Cells
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    • v.20 no.1
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    • pp.127-135
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    • 2005
  • The uptake of putrescine, spermidine and spermine by Fortner's hamster amelanocytic melanoma AMEL-3 cells was observed in this study to be time-dependent, temperature-sensitive, pH-dependent and saturable. Metabolic poisons nullified polyamine uptake, an indication that this is an energy-requiring mechanism. The presence of $Na^+$ ions was found to be requisite to full activity. Valinomycin, gramicidin, monensin and the calcium ionophore calcimycin were also observed to inhibit the process substantially. The transporter active site would seem to contain sulfhydryl groups. Other diamines and polyamine analogues, as well as cationic diamidines, suppressed putrescine uptake. The presence of the ornithine decarboxylase inhibitor DFMO in the culture medium induced putrescine inflows. Putrescine, in turn, induced the negative expression of the carrier, thus suggesting that this influx mechanism is governed by up/down regulation. The cationic diamidine CGP 40215A and its analogue CGP039937A competitively inhibited putrescine transport, with Ki values of 1.9 and $15{\mu}M$, respectively. The role of polyamine uptake in these cultures is discussed.

Inhibition of Myoblast Differentiation by Polyamine Depletion with Methylglyoxal Bis(guanylhydrazone)

  • Cho, Hwa-Jeong;Kim, Byeong-Gee;Kim, Han-Do;Kang, Ho-Sung;Kim, Chong-Rak
    • BMB Reports
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    • v.28 no.3
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    • pp.191-196
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    • 1995
  • The role of polyamines in skeletal myoblast differentiation was investigated using the polyamine metabolic inhibitor methylglyoxal bis(guanylhydrazone)(MGBG). Concentrations of intracellular free spermidine and spermine increased 2 to 2.5-fold at the onset of myoblast fusion. The systhesis of actin, and creatine kinase activity both dramatically increased during myotube formation. However, MGBG at a concentration of 0.5 mM not only abolished the increase of intracellular free polyamines, but also reduced cell fusion to almost half the level of untreated cells, without noticeable morphological alteration. The production of actin, and creatine kinase activity were almost completely abolished by MGBG. The inhibition of myoblast fusion by MGBG was partially recovered with 0.1 mM of spermidine or spermine added externally. Results indicate that polyamines are necessary for normal myoblast differentiation. Since the first indication of myoblast differentiation is alignment of muscle cells and membrane fusion of adjacent cells, and since polyamine depletion completely inhibited the synthesis of actin, which might be associted with membranes, polyamine might be involved in myoblast differentiation through membrane reorganization events.

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SLC3A2 and SLC7A2 Mediate the Exogenous Putrescine-Induced Adipocyte Differentiation

  • Jin, Eom;Juhyun, Choi;Sung-Suk, Suh;Jong Bae, Seo
    • Molecules and Cells
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    • v.45 no.12
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    • pp.963-975
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    • 2022
  • Exogenous polyamines are able to induce life span and improve glucose homeostasis and insulin sensitivity. However, the effects of exogenous polyamines on adipocyte differentiation and which polyamine transporters mediate them have not been elucidated yet. Here, we identified for the first time that exogenous polyamines can clearly stimulate adipocyte differentiation through polyamine transporters, solute carrier family 3 member A2 (SLC3A2) and SLC7A1. Exogenous polyamines markedly promote 3T3-L1 adipocyte differentiation by increasing the intracellular lipid accumulation and the expression of both adipogenic and lipogenic genes in a concentration-dependent manner. In particular, exogenous putrescine mainly regulates adipocyte differentiation in the early and intermediate stages. Moreover, we have assessed the expression of polyamine transporter genes in 3T3-L1 preadipocytes and adipocytes. Interestingly, the putrescine-induced adipocyte differentiation was found to be significantly suppressed in response to a treatment with a polyamine transporter inhibitor (AMXT-1501). Furthermore, knockdown experiments using siRNA that specifically targeted SLC3A2 or SLC7A2, revealed that both SLC3A2 and SLC7A2 act as important transporters in the cellular importing of exogenous putrescine. Thus, the exogenous putrescine entering the adipocytes via cellular transporters is involved in adipogenesis through a modulation of both the mitotic clonal expansion and the expression of master transcription factors. Taken together, these results suggest that exogenous polyamines (such as putrescine) entering the adipocytes through polyamine transporters, can stimulate adipogenesis.

Effects of Methylglyoxal-bis (Guanylhydrazone) and Ethylene Synthesis Inhibitor on Adventitious Root formation from Soybean Cotyledon (Methylglyoxal-bis (Guanylhydrazone)와 에틸렌 생합성 저해제가 대두 자엽 부정근 형성에 미치는 영향)

  • 조형일;한태진;하건수;이순희;김응식
    • Korean Journal of Plant Tissue Culture
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    • v.21 no.6
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    • pp.327-332
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    • 1994
  • The effect of methylglyoxal-bis (guanylhydrazone) (MGBG) and ethylene synthesis inhibitors on adventitious root formation from soybean cotyledon in relation to ethylene production and endogenous polyamine content was investigated. Cotyledon explants cultured on rooting medium formed numerous adventitious rook on the cut surfaces after 2 weeks of culture. However when cultured on rooting medium supplemented with MGBG, the root formation was strongly inhibited, its inhibitory effect was reserved when cultured on medium with MGBG + spermine, MGBG + CoCl$_2$ and MGBG + spermine+CoC1$_2$. A slight reversion of the rooting inhibition was observed in 10$^{-3}$ M MGBG +10$^{-5}$ M spermine treatment, whereas it caused a significant effect in 10$^{-3}$ M MGBG +10$^{-4}$ M treatment .Ethylene production and endogenous polymine content was investgated in 10$^{-3}$ M MGBG , 10$^{-3}$ M MGBG +10$^{-5}$ Mspermine, 10$^{-3}$ M MGBG +10$^{-4}$ M CoCl$_2$and 10$^{-3}$ M MGBG +10$^{-5}$ M spermine +10$^{-4}$ M CoCl$_2$treatments. Ethylene production highest in 10$^{-3}$ M MGBG +10$^{-5}$ M spermine treatment was higher than control. In 10$^{-3}$ M MGBG +10$^{-5}$ M spermine + 10$^{-4}$ M CoCl$_2$ treatment, ethilene production was lowest, whereas polyamine level was highest.

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