M K Lee

Chungbuk National University, South Korea

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Publications (17)38.86 Total impact

  • J S Ro, S S Lee, K S Lee, M K Lee
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    ABSTRACT: The inhibitory effects of coptisine, a protoberberine isoquinoline alkaloid, on type A and type B monoamine oxidase (MAO-A and MAO-B) activities in mouse brain were investigated. Coptisine showed an inhibitory effect on MAO-A activity in a concentration-dependent manner using a substrate kynuramine, but coptisine did not inhibit MAO-B activity. Coptisine exhibited 54.3% inhibition of MAO-A activity at 2 microM. The values of Km and Vmax of MAO-A were 151.9 +/- 0.6 microM and 0.40 +/- 0.03 nmol/min/mg protein, respectively (n=5). Coptisine competitively inhibited MAO-A activity with kynuramine. The Ki value of coptisine was 3.3 microM. The inhibition of MAO-A by coptisine was found to be reversible by dialysis of the incubation mixture. These results suggest that coptisine is a potent reversible inhibitor of MAO-A, and that coptisine functions to regulate the catecholamine content.
    Life Sciences 01/2002; 70(6):639-45. · 2.56 Impact Factor
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    ABSTRACT: The effects of benzylisoquinoline compounds such as ethaverine, laudanosine, and tetrahydropapaverine on monoamine oxidase (MAO, EC 1.4.3.4) activity in mouse brain were investigated. Ethaverine showed an inhibition of MAO activity in a concentration-dependent manner (57.6% inhibition at 40 microm). Papaverine also inhibited MAO activity (38.1% inhibition at 40 microM). However, laudanosine and tetrahydropapaverine did not inhibit MAO activity. The IC50 value of ethaverine for MAO was 25.5 microm. Ethaverine non-competitively inhibited MAO activity with a substrate kynuramine. The Ki value for ethaverine was 11.9 microM. In addition, ethaverine proved to preferentially inhibit type B MAO activity in a concentration-dependent manner, with an IC50 value of 32.8 microm. These results suggest that ethaverine partially contributes to the regulation of catecholamine content.
    Biological & Pharmaceutical Bulletin 08/2001; 24(7):838-40. · 1.85 Impact Factor
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    ABSTRACT: Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.
    International Immunopharmacology 08/2001; 1(7):1275-84. · 2.42 Impact Factor
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    ABSTRACT: The effects of 2-chloro-3-(4-acetophenyl)-amino-1,4-naphthoquinone (NQ301), an antithrombotic agent, on aggregation, binding of fibrinogen to glycoprotein (GP)IIb/IIIa complex and intracellular signals were investigated using human platelets. NQ301 significantly inhibited the collagen-, thrombin-, arachidonic acid-, thapsigargin- and calcium ionophore A23187-induced aggregation of washed human platelets with IC50 values of 13.0+/-0.1, 11.2+/-0.5, 21.0+/-0.9, 3.8+/-0.1 and 46.2+/-0.8 microM, respectively. NQ301 also significantly inhibited FITC-conjugated fibrinogen binding to human platelet surface GPIIb/IIIa complex, but failed to inhibit the fibrinogen binding to purified GPIIb/IIIa complex. These data demonstrate that NQ301 inhibits platelet aggregation by suppression of the intracellular pathway, rather than by direct inhibition of fibrinogen-GPIIb/IIIa complex binding. NQ301 significantly inhibited the increase of cytosolic Ca2+ concentration and ATP secretion, and also significantly increased platelet cAMP levels in the activated platelets. These results suggest that the antiplatelet activity of NQ301 may be mediated by inhibition of cytosolic Ca2+ mobilization, enhancement of cAMP production and inhibition of ATP secretion in activated platelets.
    Biological & Pharmaceutical Bulletin 07/2001; 24(6):618-22. · 1.85 Impact Factor
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    ABSTRACT: Interleukin-6 (IL-6) is known as a proinflammatory cytokine involved in immune response, inflammation, and hematopoiesis. Inhibitory effects of anti-inflammatory drugs on IL-6 bioactivity using IL-6-dependent hybridoma have been evaluated. Three out of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) showed IC50 values of less than 100 microM, which were in the order of oxyphenylbutazone hydrate (IC50=7.5 microM)>meclofenamic acid sodium salt (31.9 microM)>sulindac (74.9 microM). Steroidal anti-inflammatory drugs (SAIDs) exhibited significant inhibitory effects at 100 microM on the IL-6 bioactivity, and their inhibitory potencies were in the order of budesonide (IC50=2.2 microM)>hydrocortisone 21-hemisuccinate (6.7 microM), prednisolone (7.5 microM), betamethasone (10.9 microM)>dexamethasone (18.9 microM) and triamcinolone acetonide (24.1 microM). The results would provide an additional mechanism by which anti-inflammatory drugs display their anti-inflammatory and immunosuppressive effects at higher concentrations.
    Biological & Pharmaceutical Bulletin 06/2001; 24(6):701-3. · 1.85 Impact Factor
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    ABSTRACT: Early T progenitors in the thymus have been reported to have the capacity to develop into B cells, thymic dendritic cells, and NK cells. Here we describe conditions that induce early T progenitors to develop into macrophages. Initially, we observed that early T progenitors could be induced to develop into macrophages by cytokines produced from a thymic stromal cell line, TFGD, and later we found that the cytokine mixture of M-CSF plus IL-6 plus IL-7 also induced macrophage differentiation from pro-T cells. M-CSF by itself was unable to induce macrophage differentiation from early T progenitors. To correlate this observation with the developmental potential of early T progenitors, mouse embryonic thymocytes were sorted into four populations, pro-T1 to pro-T4, based on the expression of CD44 and CD25, and then cultured with TFGD culture supernatant. We found that pro-T1 and pro-T2 cells, but not pro-T3 and pro-T4 cells, generate macrophages. Limiting dilution analysis of the differentiation capability of sorted pro-T2 cells also confirmed that pro-T2 cells could generate macrophages. These results suggest that T cells and thymic macrophages could originate from a common intrathymic precursor.
    The Journal of Immunology 06/2001; 166(10):5964-9. · 5.52 Impact Factor
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    ABSTRACT: The inhibitory effects of ethaverine on dopamine content in PC12 cells were investigated. Ethaverine decreased dopamine content in a concentration-dependent manner in PC12 cells and showed 33.6% inhibition of dopamine content at a concentration of 1.0 microM for 24-48 h. The IC50 value of ethaverine was 1.4 microM. Dopamine content was lowered at 6h and reached a minimal level at 12h after exposure to ethaverine at 2.0 microM. The decreased dopamine level was maintained up to 48 h and then recovered to the control level at about 72 h. Tyrosine hydroxylase (TH) was inhibited at 6 h following treatment with ethaverine in PC12 cells and the activity was maintained at a reduced level up to 36 h (12-22% inhibition at 2.0 microM). These results indicate that ethaverine leads to a decrease in dopamine content by inhibition of TH activity.
    Biological & Pharmaceutical Bulletin 02/2001; 24(1):103-5. · 1.85 Impact Factor
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    ABSTRACT: The possibility of NQ12 (2-chloro-3-[4-(ethylcarboxy)-phenyl]-amino-1,4-naphthoquinone) as a novel antithrombotic agent and its mode of action were investigated. The effects of NQ12 on platelet aggregation in human platelet-rich plasma in vitro, in rats ex vivo, and on murine pulmonary thrombosis in vivo, as well as the mode of antithrombotic action were examined. NQ12 potently inhibited ADP-, collagen-, epinephrine-, and calcium ionophore-induced human platelet aggregations in vitro concentration-dependently. NQ12 significantly inhibited rat platelet aggregation in an ex vivo study. NQ12 prevented murine pulmonary thrombosis in a dose-dependent manner. However, NQ12 did not affect coagulation parameters such as activated partial thromboplastin time, prothrombin time, and thrombin time. NQ12 inhibited fibrinogen binding to the platelet surface GPIIb/IIIa receptor, but failed to inhibit binding to the purified GPIIb/IIIa receptor. Thromboxane B(2) formation caused by thrombin or collagen was inhibited significantly by NQ12. The phosphoinositide breakdown induced by thrombin or collagen was inhibited concentration-dependently by NQ12. These results suggest that NQ12 may be a promising antithrombotic agent, and its antithrombotic activity may be due to antiplatelet aggregation activity, which may result from the inhibition of phosphoinositide breakdown and thromboxane A(2) formation.
    Biochemical Pharmacology 11/2000; 60(7):1001-8. · 4.58 Impact Factor
  • J S Shin, E I Kim, M Kai, M K Lee
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    ABSTRACT: Berberine and palmatine exhibit a mild and competitive inhibition on bovine adrenal tyrosine hydroxylase (EC 1.14.16.2; TH). In this study, the inhibitory effects of protoberberine alkaloids (such as berberine, palmatine and coptisine) on dopamine biosynthesis in PC12 cells were investigated. Treatment with berberine and palmatine showed 53.7% and 61.0% inhibition of dopamine content in PC12 cells at a concentration of 20 microM for 24 hr, respectively. However, coptisine did not reduce dopamine content. The IC50 values of berberine and palmatine were 18.6 microM and 7.9 microM. Dopamine content was lowered at 6 hr and reached the minimal level at 24 hr after exposure to berberine and palmatine at 20 microM. The decreased dopamine level was maintained up to 48 hr, and then recovered to the control level at about 72 hr. TH activity was inhibited at 6 hr following treatment with berberine and palmatine, and was maintained at a reduced level up to 36 hr in PC12 cells (21-27% inhibition at 20 microM), whereas TH mRNA level was not found to alter for 24 hr. However, the intracellular Ca2+ concentration decreased by treatment with berberine and palmatine at 20 microM by 22-26% inhibition relative to the control level in PC12 cells. These results give evidence that berberine and palmatine lead to decreased dopamine content by inhibition of TH activity but not by regulation of TH gene expression in PC12 cells.
    Neurochemical Research 04/2000; 25(3):363-8. · 2.13 Impact Factor
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    S S Lee, Y H Kim, M K Lee
    Archives of Pharmacal Research 11/1999; 22(5):529-31. · 1.54 Impact Factor
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    ABSTRACT: The present study was undertaken to investigate the effects of ginsenosides on bovine adrenal tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. Ginsenoside-Rb1, Rc, Re and Rg, inhibited the TH activity by 51.5, 25.4, 31.3, 44.3 and 43.3%, respectively, at a concentration of 80 microg/ml. Ginsenoside-Rb1, Rc, Re and Rg1 exhibited noncompetitive inhibition of TH activity with a substrate L-tyrosine. From these results, it is presumed that the effects of ginsenosides on TH activity observed in vitro might be also produced in vivo, and thereby the inhibitory effects of ginsenosides on TH activity may be partially responsible for the antidopaminergic action of ginsenosides by reducing the availability of dopamine at the presynaptic dopamine receptor in vivo.
    Journal of Ethnopharmacology 08/1999; 66(1):107-11. · 2.94 Impact Factor
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    ABSTRACT: The inhibitory effects of (+/-)-higenamine, a benzylisoquinoline alkaloid, on dopamine biosynthesis in PC12 cells were investigated. Higenamine decreased the intracellular dopamine content dose-dependently and showed 55.2% inhibition of dopamine content in PC12 cells at a concentration of 20 microM with 24 h incubation. The IC50 value of higenamine was 18.2 microM. Dopamine content was lowered and reached minimal level at 12-24 h after exposure to higenamine. In this condition, tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, was also inhibited by the treatment of higenamine in PC12 cells (21.9% inhibition at 20 microM). Higenamine at 20 microM lowered the intracellular Ca2+ concentration by 33.1% inhibition relative to control in PC12 cells. These results suggest that the inhibition of tyrosine hydroxylase activity by higenamine might partially contribute to the decrease in dopamine content in PC12 cells.
    Planta Medica 07/1999; 65(5):452-5. · 2.35 Impact Factor
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    ABSTRACT: Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.
    Archives of Pharmacal Research 07/1999; 22(3):324-6. · 1.54 Impact Factor
  • M Kai, H Iida, H Nohta, M K Lee, K Ohta
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    ABSTRACT: A pre-column derivatization method using a fluorogenic reagent, 1,2-diphenylethylenediamine (DPE) was studied for the sensitive HPLC determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), which are biosubstances used in the diagnosis of several diseases. For the quantitative determination, the biogenic indole compounds were converted to their corresponding fluorescent derivatives with DPE in the presence of potassium hexacyanoferrate (III) at room temperature, and then the derivatives were separated by reversed-phase liquid chromatography with fluorescence detection. The chromatographic detection limits of the fluorescent peaks at a signal-to-noise ratio of 3 were 0.3 fmol for 5-HT and 0.2 fmol for 5-HIAA. The proposed method permits the simultaneous quantification of 5-HT and 5-HIAA at concentrations higher than 2.4 nM in human urine without a clean-up procedure.
    Journal of chromatography. B, Biomedical sciences and applications 01/1999; 720(1-2):25-31.
  • J S Shin, K T Kim, M K Lee
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    ABSTRACT: The effects of bulbocapnine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis in PC12 cells were investigated. Bulbocapnine showed 45.2% inhibition on dopamine content in PC12 cells at a concentration of 20 microM for 12 h. The IC50 value of bulbocapnine was 26.7 microM. Bulbocapnine at concentrations up to 80 microM was not cytotoxic towards PC12 cells. Tyrosine hydroxylase (TH) activity was inhibited by the treatment of bulbocapnine in PC12 cells (24.4% inhibition at 20 microM). Bulbocapnine at 20 microM also decreased the intracellular Ca2+ concentration by 12.9% inhibition relative to control in PC12 cells. However, TH mRNA level was not altered by bulbocapnine treatment. These results suggest that the inhibition of TH activity by bulbocapnine might be involved in at least one component of the reduction of dopamine biosynthesis in PC12 cells.
    Neuroscience Letters 04/1998; 244(3):161-4. · 2.03 Impact Factor
  • J S Shin, S S Lee, M K Lee
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    ABSTRACT: The effects of noscapine, a phthalide isoquinoline alkaloid, on dopamine biosynthesis and tyrosine hydroxylase (TH) activity in PC12 cells were investigated. Noscapine showed 74.6% inhibition on dopamine content in PC12 cells at a concentration of 20 muM. IC(50) of noscapine was 6.8 muM. TH activity was inhibited by the treatment of noscapine in PC12 cells (20.9% inhibition at 20 muM). Therefore, the inhibition of TH activity by noscapine might be involved in at least one component of the reduction of dopamine biosynthesis in PC12 cells.
    Archives of Pharmacal Research 11/1997; 20(5):510-2. · 1.54 Impact Factor
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    ABSTRACT: The inhibitory effects of bulbocapnine, an aporphine isoquinoline alkaloid, on bovine adrenal tyrosine hydroxylase (TH) were investigated. Bulbocapnine had an inhibitory effect on the enzyme (43.6% inhibition at concentration of 200 microM). Bulbocapnine exhibited uncompetitive inhibition on bovine adrenal TH with a substrate L-tyrosine. The Ki value was found to be 0.20 mM.
    Planta Medica 09/1997; 63(4):362-3. · 2.35 Impact Factor