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GAP JUNCTION, A BIOMARKER FOR CANCER AND CHEMOPREVENTION: PREVENTIVE EFFECT OF EPICATECHIN AND GINSENOSIDE $Rb_$ ON THE INHIBITION OF GAP JUNCTIONAL INTERCULLULAR COMMUNICATION BY TPA AND $H_2O_2$

  • Kang, Kyung-Sun;Lee, Yong-Soom
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05b
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    • pp.59-72
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    • 2002
  • The anticarcinogenic effects of epicatechin(EC) and ginsenoside Rb2(Rb2), which are major components of green tea and Korea ginsen, respectively, were investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. 12-O-Tetradecanoylphorbol-13-accetate (TPA) and hydrogen preoxide, known as cancer promoters, inhibited GJIC in the epithelial cells as determined by the scrape loading/dye transfer assay, fluorescence redistribution assay after photobleaching, and immunofluorescent staining of connexin 43 using a laser confocal microscope. The inhibition of GJIC by TPA and H2O2 was prevented with treatment of Rb2 or Ec. The effect of EC on GJIC was stronger in TPA-treated cells than in H2O2-treated cells, while the effect of Rb2 was opoosite to that of EC. EC, at the concentration of 27.8$\mu$g/ml, prevented the TPA-induced GJIC inhibition by about 60%. Rb2, at the concentration of 277$\mu$g/ml, recovered the H2O2-induced GJIC inhibition by about 60%. These results suggest that Rb2 and EC may prevent human cancers by preventing the down-regulation of GJIC during the cancer promotion phase and that the anticancer effect of green tea and Korea ginseng may come from the major respective conponents, EC and Rb2.

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Inhibition of Seed Germination and Induction of Systemic Disease Resistance by Pseudomonas chlororaphis O6 Requires Phenazine Production Regulated by the Global Regulator, GacS

  • Kang, Beom-Ryong;Han, Song-Hee;Zdor, Rob E.;Anderson, Anne J.;Spencer, Matt;Yang, Kwang-Yeol;Kim, Yong-Hwan;Lee, Myung-Chul;Cho, Baik-Ho;Kim, Young-Cheol
    • Journal of Microbiology and Biotechnology
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    • v.17 no.4
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    • pp.586-593
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    • 2007
  • Seed coating by a phenazine-producing bacterium, Pseudomonas chlororaphis O6, induced dose-dependent inhibition of germination in wheat and barley seeds, but did not inhibit germination of rice or cucumber seeds. In wheat seedlings grown from inoculated seeds, phenazine production levels near the seed were higher than in the roots. Deletion of the gacS gene reduced transcription from the genes required for phenazine synthesis, the regulatory phzI gene and the biosynthetic phzA gene. The inhibition of seed germination and the induction of systemic disease resistance against a bacterial soft-rot pathogen, Erwinia carotovora subsp. carotovora, were impaired in the gacS and phzA mutants of P chlororaphis O6. Culture filtrates of the gacS and phzA mutants of P. chlororaphis O6 did not inhibit seed germination of wheat, whereas that of the wild-type was inhibitory. Our results showed that the production of phenazines by P. chlororaphis O6 was correlated with reduced germination of barley and wheat seeds, and the level of systemic resistance in tobacco against E. carotovora.

Regulation of BAD Protein by PKA, PKCδ and Phosphatases in Adult Rat Cardiac Myocytes Subjected to Oxidative Stress

  • Cieslak, Danuta;Lazou, Antigone
    • Molecules and Cells
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    • v.24 no.2
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    • pp.224-231
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    • 2007
  • $H_2O_2$, as an example of oxidative stress, induces cardiac myocyte apoptosis. Bcl-2 family proteins are key regulators of the apoptotic response while their functions can be regulated by post-translational modifications including phosphorylation, dimerization or proteolytic cleavage. In this study, we examined the role of various protein kinases in regulating total BAD protein levels in adult rat cardiac myocytes undergoing apoptosis. Stimulation with 0.1 mM $H_2O_2$, which induces apoptosis, resulted in a marked down-regulation of BAD protein, which is attributed to cleavage by caspases since it can be restored in the presence of a general caspase inhibitor. Inhibition of PKC, p38-MAPK, ERK1/2 and PI-3-K did not influence the reduced BAD protein levels observed after stimulation with $H_2O_2$. On the contrary, inhibition of PKA or specifically $PKC{\delta}$ resulted in up-regulation of BAD. Decreased caspase 3 activity was observed in $H_2O_2$ treated cells after inhibition of PKA or $PKC{\delta}$ whereas inhibition of PKA also resulted in improved cell survival. Furthermore, addition of okadaic acid to inhibit selected phosphatases resulted in enhanced BAD cleavage. These data suggest that, during oxidative stress-induced cardiac myocyte apoptosis, there is a caspase-dependent down-regulation of BAD protein, which seems to be regulated by coordinated action of PKA, $PKC{\delta}$ and phosphatases.

Effect of Scutellaria Baicalensis Georgi Extraction (SbGE) on H2O2-induced Inhibition of Phosphate Transport in Renal Epithelial Cells (황금약침액(黃芩藥鍼液)이 신장상피세포(腎臟上皮細胞)에서의 H2O2에 의한 인산염(燐酸鹽) 운반(運搬)의 억제(抑制)에 미치는 영향(影響))

  • Cho, Eun-jin;Youn, Hyoun-min;Jang, Kyung-jeon;Song, Choon-bo;Ahn, Chang-beobm
    • Journal of Acupuncture Research
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    • v.19 no.4
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    • pp.190-199
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    • 2002
  • Objective : This study was performed to determine if Scutellaria balicalensis Georgi extract (SbGE) prevents oxidant-induced membrane transport dysfunction in renal tubular cells. Methods : Membrane transport function was estimated by measuring $Na^+$-dependent inorganic phosphate transport in opossum kidney (OK) cells. $H_2O_2$ inhibited phosphate transport in a dose-dependent manner. Results : The inhibitory effect of $H_2O_2$ was significantly prevented SbGE over concentration range of 0.005-0.05%. $H_2O_2$ caused ATP depletion, which was prevented by SbGE. $H_2O_2$ induced the loss of mitochondrial function as evidenced by decreased MTT reduction and its effect was prevented by SbGE. The $H_2O_2$-induced inhibition of phosphate transport was not affected by a potent antioxidant DPPD, but the inhibition was prevented by an iron chelator deferoxamine, suggesting that $H_2O_2$ inhibits $Na^+$-dependent phosphate transport via an iron-dependent nonperoxidative mechanism in renal tubular cells. Conclusion : These data suggest that SbGE may exert the protective effect against oxidant-induced membrane transport dysfunction by a mechanism similar to iron chelators in renal epithelial cells. However, furher studies should be carried out to find the active ingredient(s) of SbGE that exerts the protective effect.

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Catalytic Deep Oxidation of Volatile Organic Compound Toluene over CuO/γ-Al2O3 Catalysts at Lower Temperatures (CuO/γ-Al2O3 촉매상에서 휘발성 유기화합물 톨루엔의 저온산화)

  • Kim Sang-Hwan;Kim Jae-Sik;Yang Hee-Sung;Y Vu Trinh Nhu;Park Hyung-Sang
    • Journal of Korean Society for Atmospheric Environment
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    • v.23 no.1
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    • pp.64-73
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    • 2007
  • The catalytic activity of transition metals (Cu, Co, Mn, Fe and Ni) supported on ${\gamma}-Al_2O_3$ for the oxidation of toluene was investigated in the microreactor of fixed-bed type. The catalytic activity of transition metals for the oxidation of toluene turned out to be increasing in the order of Ni$Cu/{\gamma}-Al_2O_3$ catalysts for the oxidation of toluene increased with the increasing loadings of copper, reached the maximum activity at 5% loadings of copper, and decreased with higher loadings of copper in the catalysts. The activity of $Cu/{\gamma}-Al_2O_3$ catalysts for the oxidation of toluene decreased with the increasing calcination temperatures. This might result from the decreasing surface area of catalysts due to the sintering of copper oxide as well as ${\gamma}-Al_2O_3$ supports. The 5wt% $Cu/{\gamma}-Al_2O_3$ catalysts calcined at $400^{\circ}C$ for 4 hrs in the air showed the highest activity for the oxidation of toluene. Mutual inhibition was observed for the binary mixture of toluene and xylene. The activity of the easy-to-oxidize toluene was greatly decreased while the difficult-to-oxidize xylene was slightly decreased in the binary mixture of toluene and xylene. It might suggest that the inhibition of toluene and xylene in the binary mixture resulted from the competitive adsorption for the adsorbed oxygen on the catalytic surface.

Effect of Salviae-radix on oxidant-induced impairment of membrane transport function in renal tubules (Oxidant에 의한 신장세뇨관 물질이동계의 장애에 대한 단삼(丹參)의 효과)

  • Kim, Sang-Beum;Jeong, Ji-Cheon
    • The Journal of Internal Korean Medicine
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    • v.18 no.1
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    • pp.147-155
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    • 1997
  • This study was undertaken to determine whether Salviae-radix (SVR) exraction exerts benefical effect against oxidant-induced inhibition of tetraethylammonium (TEA) uptake which is actively secreted by renal proximal tubules. TEA uptake increased as function of incubation time to 60 min. When renal cortical slices were exposed to 50 mM $H_2O_2$, TEA uptake was significantly inhibited. The inhibition was significantly protected by addition of 0.5% SVR extraction. The benefical effect of SVR was dose-dependent over the concentration range of 0.1-1%; $H_2O_2$ (50 mM)-induced inhibition of TEA uptake was completely protected by 0.5-1% SVR extraction. $H_2O_2$ increased LDH release which was accompanied by an increase in lipid peroxidation in renal cortical slices. These changes were prevented by 0.5% SVR. These results suggest that SVR exerts benefical effect against oxidant-induced impairment of membrane transport function, this effect may be due to by an antioxidant action.

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Inhibition of Lens Aldose Reductase by Medicinal Plants (수종 생약에 의한 Lens Aldose Reductase의 억제)

  • Jeong, Do-Rae;Park, Woong-Yang;Lee, Seung-Ho;Lee, Kyong-Soon;Ro, Jai-Seup
    • Korean Journal of Pharmacognosy
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    • v.24 no.1
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    • pp.58-62
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    • 1993
  • To search for inhibitory activities for lens aldose reductase, twenty two medicinal plants were tested by the method of bovine lens aldose reductase inhibition test. In this test Rubia akane(68%), Artemisia selengensis(61%), Lespedeza cuneata (58%), Ligustrum lucidum(58%), Viola patrinii(58%) extracts were shown to have aldose reductase inhibitory activity. From the radix of Rubia akane, $2-methyl-1,\;3,\;6-trihydroxy-9,\;10-anthraquinone-3-O-(6'-O-acetyl)-{\alpha}-rhamnosyl-(1{\rightarrow}2)-{\beta}-D-glucoside$ was isolated and the $IC_{50}$ of this compound in the aldose reductase inhibition test was about $1.2{\times}10^{-6}M$.

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Substrate Utilization Patterns During BTEX Biodegradation by an o-Xylene-Degrading Bacterium Ralstonia sp. PHS1

  • Lee, Sung-Kuk;Lee, Sun-Bok
    • Journal of Microbiology and Biotechnology
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    • v.12 no.6
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    • pp.909-915
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    • 2002
  • The biodegradation of BTEX components (benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene) individually and in mixtures was investigated using the o-xylene-degrading thermo-tolerant bacterium Ralsronia sp. strain PHS1 , which utilizes benzene, toluene, ethylbenzene, or o-xylene as its sole carbon source. The results showed that as a single substrate for growth, benzene was superior to both toluene and ethylbenzene. While growth inhibition was severe at higher o-xylene concentrations, no inhibition was observed (up to 100 mg $l^-1$) with ethylbenzene. In mixtures of BTEX compounds, the PHS1 culture was shown to degrade all six BTEX components and the degradation rates were in the order of benzene, toluene, o-xylene, ethylbenzene, and m- and p-xylene. m-Xylene and p-xylene were found to be co-metabolized by this microorganism in the presence of the growth-supporting BTEX compounds. In binary mixtures containing the growth substrates (benzene, toluene, ethylbenzene. and o-xylene), PHS1 degraded each BTEX compound faster when it was alone than when it was a component of a BTEX mixture, although the degree of inhibition varied according to the substrates in the mixtures. p-Xylene was shown to be the most potent inhibitor of BTEX biodegradation in binary mixtures. On the other hand, the degradation rates of the non-growth substrates (m-xylene and p-xylene) were significantly enhanced by the addition of growth substrates. The substrate utilization patterns between PHS1 and other microorganisms were also examined.

Microscopic Study of Decomposition-Inhibition in Stabilized $ClO_2$ Gas in Kidney of Rat with Passage of Time (시간경과에 따른 안정화 이산화염소(Stabilized $ClO_2$)의 콩팥조직 부패억제에 대한 현미경적 연구)

  • Hwang, Kyu-Sung;Choi, Ki-Ju;Paik, Doo-Jin;Lim, Do-Seon
    • Applied Microscopy
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    • v.38 no.3
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    • pp.259-264
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    • 2008
  • The stabilized $ClO_2$ gas has been used for many years by the food industry as a strong oxidizing and sanitizing agent that has broad and high biocidal effectiveness. Therefore, "stabilized $ClO_2$" gas may be used in fields of disinfectant and sterilization. But, there have been few studies on the decomposition-inhibition effect of stabilized $ClO_2$ gas with passage of time. The main purpose of this study was to examine the decomposition-inhibition effect of stabilized $ClO_2$ gas and the morphological change of kidney by measuring of the light and electron microscope. Sprague-Dawley (SD) rats weighting from 230 gm to 250 gm were used as experimental animals. Under ether anesthesia, the right kidney of rat was obtained. Put each sample in $37^{\circ}C$ and humidity $80{\pm}5%$ incubator, we obtained each sample after 0 day, 1 day, 2 days, 3 days, 4 days and 5 days. We proceeded the observation of light and electron microscope. The results obtained in this study reveal that stabilized $ClO_2$ gas is an effective decomposition inhibitor until 2 days that was conducted at $37^{\circ}C$ and humidity $80{\pm}5%$ conditions.

Glycosyl glycerides from hydroponic Panax ginseng inhibited NO production in lipopolysaccharide-stimulated RAW264.7 cells

  • Cha, Byeong-Ju;Park, Ji-Hae;Shrestha, Sabina;Baek, Nam-In;Lee, Sang Min;Lee, Tae Hoon;Kim, Jiyoung;Kim, Geum-Soog;Kim, Seung-Yu;Lee, Dae-Young
    • Journal of Ginseng Research
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    • v.39 no.2
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    • pp.162-168
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    • 2015
  • Background: Although the aerial parts of hydroponic Panax ginseng are reported to contain higher contents of total ginsenosides than those of roots, the isolation and identification of active metabolites from the aerial parts of hydroponic P. ginseng have not been carried out so far. Methods: The aerial parts of hydroponic P. ginseng were applied on repeated silica gel and octadecylsilane columns to yield four glycosyl glycerides (Compounds 1-4), which were identified based on nuclear magnetic resonance, infrared, fast atom bombardment mass spectrometry, and gas chromatography/mass spectrometry data. Compounds 1-4 were evaluated for inhibition activity on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results and conclusion: The glycosyl glycerides were identified to be (2S)-1-O-7(Z),10(Z),13(Z)-hexadecatrienoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (1), (2S)-1-O-linolenoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (2), (2S)-1-O-linolenoyl-2-O-linolenoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (3), and 2(S)-1-O-linoleoyl-2-O-linoleoyl-3-O-${\beta}$-$\small{D}$-galactopyranosyl-sn-glycerol (4). Compounds 1 and 2 showed moderate inhibition activity on NO production in LPS-stimulated RAW264.7 cells [half maximal inhibitory concentration ($IC_{50}$): $63.8{\pm}6.4{\mu}M$ and $59.4{\pm}6.8{\mu}M$, respectively] without cytotoxicity at concentrations < $100{\mu}M$, whereas Compounds 3 and 4 showed good inhibition effect ($IC_{50}$: $7.7{\pm}0.6{\mu}M$ and $8.0{\pm}0.9{\mu}M$, respectively) without cytotoxicity at concentrations < $20{\mu}M$. All isolated compounds showed reduced messenger RNA (mRNA) expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and tumor necrosis factor-${\alpha}$ in LPS-induced macrophage cells with strong inhibition of mRNA activity observed for Compounds 3 and 4.