• Title/Summary/Keyword: inhibitory mechanism

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Inhibitory Effect of Nicotine on Apoptosis Induced by Endoplasmic Reticulum Stress

  • Lee, Dong-Hee
    • Biomolecules & Therapeutics
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    • v.15 no.4
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    • pp.240-244
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    • 2007
  • Cigarette smoking causes serious health problems in humans, especially if smoking habits are established during their adolescence. Nicotine is known to mutate DNA and interfere with apoptosis. Apoptosis is considered as a potent defense mechanism against cellular damaging agents. This study aims to investigate the effect of nicotine on the progression of apoptosis induced under ER stress conditions using four different established cell lines: HEK293, 3T3-L1, C2C12, and HepG2. When treated with nicotine, the progression of apoptosis was notably inhibited in the four cell lines according to the assays of caspase-3 activation and DNA fragmentation. In ER-stressed cells, nicotine appears to inhibit the progression of apoptosis in a concentration-dependent manner. When cells were treated with nicotine prior to ER stress, GRP94 level significantly increased compared to other ER stress markers of PDI and GRP78. This observation suggests that the inhibitory effect of nicotine may results from up-regulation of GRP94, an anti-apoptotic chaperone, under nicotine treatment. Taken together, the present study strongly implies that nicotine may inhibit apoptosis, caused by prolonged ER stress, based on promotion of GRP94 expression.

Effect of Gleditsiae Spina on Proliferation of Transplanted-L1210 cells in Mice (조각자가 생쥐에 이식된 L1210 세포의 증식에 미치는 영향)

  • 조선경;은재순;김대근;소준노;오찬호;송정모
    • The Journal of Korean Medicine
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    • v.22 no.4
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    • pp.37-44
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    • 2001
  • Objectives : Cellular death by apoptosis is an active process, depending on gene transcription and protein synthesis. It was reported that nitric oxide can induce apoptosis in several cancer cell-lines. We have previously observed that proliferation of Ll210 cells was inhibited by the administration of Gleditsiae Spina water extract (GE). In this present study, the mechanism of inhibitory action on the proliferation of L l210 cells was examined. Methods : The cell proliferation was determined by MTT assay and DNA fragmentation was determined by a flow cytometry. Results : The administration of GE decreased proliferation of L1210 cells and enhanced DNA fragmentation in vivo system. DNA fragmentation of L1210 cells was enhanced by co-culture of peritoneal macrophages obtained from GE-administered mice in vitro and it was partly inhibited by L-NMMA, nitric oxide synthetase inhibitor. In addition, GE increased nitric oxide production from peritoneal macrophages of L1210-transplanted mice. Conclusions : These results suggest that the inhibitory action of GE on proliferation of transplanted-L1210 cells is partly caused by an induction of apoptosis via production of nitric oxide in macrophages.

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Anti-Candida Activity of YH-1715R, a New Triazole Derivative

  • Park, Kang-Sik;Kang, Heui-Il;Lee, Jong-Wook;Paik, Young-Ki
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.693-697
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    • 2004
  • YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol-3-yl-thio)-1-( 1H-1,2,4-triazol-l-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol $14\alpha$-demethylase (14$\alpha$-DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14a-DM with an $IC_{50}$ of 0.015 $\mu$M and 0.01$8\mu$M, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a $K_i$ of 0.0533$\mu$M and 0.0975$\mu$M.

Study on the Effect of Gamiyukmijihwang-tang on the Brain damage (가미육미지황탕이 뇌신경세포 손상 및 뇌허혈 병태 모델에 미치는 영향)

  • Kim Jin hyung;Kim Yun Sik;Seol In Chan;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.467-475
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    • 2003
  • This studt was investigated to prove the effect of GMYM on the brain damage. The results were as follows; 1. GMYM showed significantly inhibitory effect on LDH release by NMDA. AMPA and Kinate. 2. GMYM showed significantly inhibitory effect on LDH release by BSO and Fe2+. 3. GMYM decreased coma duration time in a infatal dose of KCN and showed 30% of survival rate in a fatal dose. 4. GMYM showed improvement of forelimb and hindlimb test after MCA occulusion in neurological exemination. 5. GMYM decreased ischemic area and edema incited by the MCA blood flow block. These results indicate that GMYM can be used in the brain damage sujected to brain ischemia. Further study will be needed about the functional mechanism and etc.

Inhibitory Effect of Lentinus edodes Aqua-acupuncture Solution on the Cytochrome P450 1A1 and 1A2 Activities (표고버섯 약침액(藥鍼液)이 Cytochrome P450 1A1과 1A2 활성 억제에 미치는 효과)

  • Moon, Jin-Young
    • Korean Journal of Acupuncture
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    • v.21 no.2
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    • pp.139-145
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    • 2004
  • Objectives : Inhibition of phase I enzymes such as cytochrome P450 (CYP) 1A1 or 1A2 is considered a major mechanism of protection against initiation of carcinogenesis. The inhibition of toxic enzymes and CYP were studied with so many oriental herbral medicine. Recently, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these polymers are their immunomodulation and anti cancer. But, in this study the inhibitory effect was on the aqua-acupuncture of Lentinus edodes. Materials : Lentinus edodes aqua-acupuncture solution (LEAS) was prepared and tested for the inhibition of cytochrome P450 (CYP) 1A1 and 1A2 activities. LEAS type I from fruit body of these mushrooms. Type II was extracted from cultured broth of Lentinus edodes mycelum. Results : LEAS type I and type II were significantly inhibited CYP 1A1 and 1A2 enzymes at concentration of 5.0 and 10.0 mg/ml. Conclusion : These results suggested that LEAS may act as block agent against carcinogenesis by inhibition of phase I enzymes.

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Effects of Electric and Magnetic Fields to Seed Germination and Its Early Growth (전계와 자계가 식물씨앗의 발아와 초기생장에 미치는 영향)

  • Moon, Jae-Duk;Kyon, Nam-Yul
    • The Transactions of the Korean Institute of Electrical Engineers C
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    • v.55 no.6
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    • pp.328-333
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    • 2006
  • All the plants on earth live under an electric and magnetic field because the earth is a magnet and there is an electric field between the charged cloud and the ground. It has been reported that electromagnetic fields influence both the activation of ions and polarization of dipoles in living cells of seeds and plants, though the mechanism of these actions is still poorly understood. In this paper, the effects of the electric and magnetic fields and exposure times to the germination of several vegetable seeds and its early growth have been investigated experimentally to find out the feasibility of a plant factory for mass production of clean and unpolluted vegetables. The germination rate and the growth rate of some seeds under the fields exposed were analysed and compared with those of unexposed ones. It is found that the germination rate and its early growth rate of exposed seeds under the fields were accelerated about 1.1-1.4 and 1.7-2.2 times in maximum compared with those of unexposed ones. But, however, an inhibitory effect on germination and plant early growth were shown in the case of the higher electric and magnetic fields.

Action of Anthraquinone on Sodium-Potassium activated -ATPase in Rabbit Red Cell Membrane- (Anthraquinone이 토끼 적혈주막의 NaK ATPase웨 활성도에 대한 작용)

  • Koh, Il-Sup
    • The Korean Journal of Physiology
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    • v.11 no.1
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    • pp.1-9
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    • 1977
  • Action of anthraquinone on the sodium plus potassium activated ATPase activity in the rabbit red cell membrane has been investigated and the experiments were also designed to determine the mechanism of action of anthraquinone on the ATPase activity. The following results were obtained 1. The activity of the NaK ATPase from red cell membrane is inhibited by anthraquinone and the concentration of anthraquinone for maximal inhibition is about 5mM. 2. The ratio of inhibition of NaK ATPase by anthraquinone, with a giving concentration of sodium in the medium, is increased by raising the potassium concentration. 3. The ratio of inhibition of NaK ATPase by anthraquinone, with a given concentration of potassium in the medium, is increased by raising the sodium concentration. 4. The action of anthraquinone on the NaK ATPase activity is inhibited by calcium ions and the ratio of inhibition is increased by small amounts of calcium but almost constant by larger amounts. 5. The inhibitory action of anthraquinone on the NaK ATPase activity was not related to the amino group of lysine, the hydroxyl group of threonine or the imidazole group of histidine. 6. The inhibitory action of anthraquinone on the ATPase activity is due to sulfhydryl group or the carboxyl group of the enzyme of NaK ATPase.

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Inhibitory Effects of Paeonol on Morphine-Induced Locomotor Sensitization and Conditioned Place Preference in Mice

  • Eun, Jae-Soon;Bae, Ki-Hwan;Yun, Yeo-Pyo;Hong, Jin-Tae;Kwon, Han-Na;Oh, Ki-Wan
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.904-910
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    • 2006
  • The inhibitory effects of paeonol, a major compound of Paeoniae radix, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated through behavioral experiments. A single administration of morphine produces hyperlocomotion. Repeated administration of morphine develops sensitization (reverse tolerance), a progressive enhancement of locomotion, which is used as a model for studying the drug-induced drug-seeking behaviors, and CPP, which is used as a model for studying drug reinforcement. Paeonol inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, paeonol inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of paeonol. These results provide evidence that paeonol exerts anti-dopaminergic activity, and it is suggested that paeonol may be useful for the prevention and therapy of these adverse actions of morphine.

New candidate for skin depigmentation: The inhibitory effect and cytotoxicity of small molecule compounds at in vitro cell culture

  • Rho, H.S;Kim, K.J.;Hwang, J.S.;H.J., Shin;Chang, H.K.;Chang, I.S.;Lee, O.S.
    • Proceedings of the SCSK Conference
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    • 2003.09b
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    • pp.174-183
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    • 2003
  • To obtain effective and safe topical depigmenting agents, we synthesized hydroxybenzoates, alkoxybenzoates, and 3,4,5-trimethoxycinnamate containing a thymol moiety and screened then for high-level inhibitory activity against melanin synthesis. Among them, 5-methyl-2-(methylethyl)phenyl (2Ε)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate (Melasolv)$^{TM}$ 4h, showed the most potent depigmenting effect ($IC_{50}$/ = 10$\mu$M) with low cytotoxicity ($IC_{50}$/ = 200$\mu$M). To find the inhibition mechanism of our candidate, various in vitro tests were performed such as DPPH assay, tyrosinase activity in mushroom or in culture cell and expression of tyrosinase, TRP-l and TRP-2. The result of this study suggested that 4h inhibited melanin synthesis by reducing the expression of tyrosinase and TRP-l at the transcriptional level in melan-a melanocytes.s.

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The Coupling Effects of Excitatory and Inhibitory Connections Between Chaotic Neurons Having Gaussian-shaped Refractory Function With Hysteresis

  • Park, Changkyu;Lee, Ju-Jang
    • 제어로봇시스템학회:학술대회논문집
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    • 1998.10a
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    • pp.356-361
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    • 1998
  • Neural Networks, modeled succinctly from the real nervous system of a living body, can be categorized into two folds; artificial neural network(ANN) and biological neural network(BNN). While the former has been developed to solve practical problems using function approximation capability, pattern classification) clustering algorithm, etc, the latter has been focused on verifying the information processing capability to which brain research gives an impetus, by mimicking real biological systems. However, BNN suffers Iron severe nonlinearities dealt with. A bridge between two neural networks is chaotic neural network(CNN), which simply delineate the real nor-vous system and comprises almost all the ANN structures by selecting parameters. Main research theme of this area is to develop an explanation tool to clarify the information processing mechanism in biological systems and its extension to engineering applications. The CNN has a Gaussian-shaped refractory function with hysteresis effect and the chaotic responses of it have been observed fur a wide range of parameter space. Through the examination of the coupling effects of excitatory and inhibitory connections, the secrets of information processing and memory structure will appear.

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