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MS-5, a Naphthalene Derivative, Induces the Apoptosis of an Ovarian Cancer Cell CAOV-3 by Interfering with the Reactive Oxygen Species Generation

  • Ma, Eunsook;Jeong, Seon-Ju;Choi, Joon-Seok;Nguyen, Thi Ha;Jeong, Chul-Ho;Joo, Sang Hoon
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.48-53
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    • 2019
  • Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS ($H_2O_2$), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

Bisphenol a induces reproductive dysfunction in male mice

  • Young-Joo, Yi;Malavige Romesha, Chandanee;Dong-Won, Seo;Jung-Min, Heo;Min, Cho;Sang-Myeong, Lee
    • Korean Journal of Agricultural Science
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    • v.48 no.4
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    • pp.935-944
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    • 2021
  • It has been suggested that bisphenol A (BPA), a known endocrine disruptor, interferes with the endocrine system, causing reproductive dysfunction. Recently, BPA has been found in waste water due to incomplete sewage purification, possibly threatening health through its ingestion via tap water. In this study, young male mice (6 - 7 weeks old) were administered water containing BPA (50 mg·kg-1) for four weeks, while control mice consumed water without BPA. Serum, epididymal spermatozoa and testicular sections were assessed after sacrificing the mice on day 28. No significant differences were obtained between the groups in the body, testis and seminal vesicle weights. However, the epididymal sperm motility and count levels were significantly reduced in BPA-fed mice. Significantly higher hepatotoxicity levels were also observed in mice ingesting BPA as compared to the control mice. The level of serum testosterone was reduced, and testicular sections revealed incomplete and irregular spermatogenesis in BPA-ingested mice. The sperm proteasomal-proteolytic activity level has been implicated in sperm function and is measured in motile spermatozoa using fluorometric substrates. High ubiquitin C-terminal hydrolase activity levels were observed in the control mice without BPA. During a mating trial, a low pregnancy rate (71.4%) was observed in females mated with males who had consumed BPA (100% in the control mice). Overall, BPA adversely affected spermatogenesis and quality, as indicated by decreased sperm motility, concentration and serum testosterone levels, resulting in reduced fertility competence.

Transformation of Populus nigra × P. maximowiczii Using Agrobacterium tumefaciens vectors (Agrobacterium tumefaciens vector를 이용(利用)한 양황철의 형질전환(形質轉換))

  • Son, Suk Gyu;Hyu, Jung Oh
    • Journal of Korean Society of Forest Science
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    • v.87 no.2
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    • pp.164-172
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    • 1998
  • This study was conducted to find the optimum transformation condition using Agrobacterium harboring promoterless GUS gene. The optimal medium for shoot induction from leaves of Populus nigra${\times}$P. maximowiczii was MS medium supplemented with $0.1mg/{\ell}$ NAA, $0.5mg/{\ell}$ BAP(94% regeneration frequency and 11.5 average number of shoot) According to the test using pBI121, the concentration of antibiotics for selection marker gene was $100mg/{\ell}$ kanamycin or $60mg/{\ell}$ geneticin in the SIM(shoot inducing medium) 3. Two weeks later, callus was induced in the SIM 3 and this callus grew up to 0.5-1cm shoots after 6 weeks in the new SIM 3. And the treatment with methylation inhibitor(5-azacytidine) led to a dramatic increase in foreign gene expression rate from 5.7% to 26.7%. The vector systems showed. different transformation efficiencies based on the fluorometric and histochemical GUS assay. In this study the vector systems used for transformation seemed to affect transformation frequency, in which pEHA101 yielded more transformants(35.9%) than LBA4404/pBI121 did(5.7%). This result indicated that pEHA101 was effective to insert the promoterless foreign gene into a poplar genome.

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Calibration and Validation of Ocean Color Satellite Imagery (해양수색 위성자료의 검.보정)

  • ;B. G. Mitchell
    • Journal of Environmental Science International
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    • v.10 no.6
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    • pp.431-436
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    • 2001
  • Variations in phytoplankton concentrations result from changes of the ocean color caused by phytoplankton pigments. Thus, ocean spectral reflectance for low chlorophyll waters are blue and high chlorophyll waters tend to have green reflectance. In the Korea region, clear waters and the open sea in the Kuroshio regions of the East China Sea have low chlorophyll. As one moves even closer In the northwestern part of the East China Sea, the situation becomes much more optically complicated, with contributions not only from higher concentration of phytoplankton, but also from sediments and dissolved materials from terrestrial and sea bottom sources. The color often approaches yellow-brown in the turbidity waters (Case Ⅱ waters). To verify satellite ocean color retrievals, or to develop new algorithms for complex case Ⅱ regions requires ship-based studies. In this study, we compared the chlorophyll retrievals from NASA's SeaWiFS sensor with chlorophyll values determined with standard fluorometric methods during two cruises on Korean NFRDI ships. For the SeaWiFS data, we used the standard NASA SeaWiFS algorithm to estimate the chlorophyll_a distribution around the Korean waters using Orbview/ SeaWiFS satellite data acquired by our HPRT station at NFRDl. We studied In find out the relationship between the measured chlorophyll_a from the ship and the estimated chlorophyll_a from the SeaWiFs satellite data around the northern part of the East China Sea, in February, and May, 2000. The relationship between the measured chlorophyll_a and the SeaWiFS chlorophyll_a shows following the equations (1) In the northern part of the East China Sea. Chlorophyll_a =0.121Ln(X) + 0.504, R²= 0.73 (1) We also determined total suspended sediment mass (55) and compared it with SeaWiFS spectral band ratio. A suspended solid algorithm was composed of in-.situ data and the ratio (L/sub WN/(490 ㎚)L/sub WN/(555 ㎚) of the SeaWiFS wavelength bands. The relationship between the measured suspended solid and the SeaWiFS band ratio shows following the equation (2) in the northern part of the East China Sea. SS = -0.703 Ln(X) + 2.237, R²= 0.62 (2) In the near future, NFRDI will develop algorithms for quantifying the ocean color properties around the Korean waters, with the data from regular ocean observations using its own research vessels and from three satellites, KOMPSAT/OSMl, Terra/MODIS and Orbview/SeaWiFS.

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Comparison of Vitamin E, Phytosterols and Fatty Acid Composition in Commercially Available Grape Seed Oils in Korea (국내 시판 포도씨유의 비타민 E, 식물성스테롤 및 지방산조성 비교)

  • Wie, Min-Jung;Seong, Ji-Hae;Jeon, Keon-Wook;Jung, Heon-Sang;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.7
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    • pp.953-956
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    • 2008
  • Grape seeds have recently been utilized for the production of seed oil. Grape seed oils (GSOs) are generating increasing interest as a functional food product since it has been shown to contain high levels of vitamin E, unsaturated fatty acids, and phytosterols. The objective of this study was to determine the compositions of vitamin E, fatty acids, and phytosterols in commercially available grape seed oils in Korea. Vitamin E was analyzed by HPLC with fluorometric detector and phytosterol and fatty acid composition was analyzed by GC. GSOs contained total vitamin E in the range of 34.6 to 66.1 mg/100 g oil and high levels of tocotrienols. The GSOs are mainly composed of linoleic acid ranging from 60 to 76%. GSOs also contained $77.0{\sim}166.9\;mg$ of phytosterols/100 g oil.

Development of herbicide-tolerant Korean rapeseed (Brassica napus L.) cultivars (한국 고유의 품종을 이용한 제초제 저항성 유채 개발)

  • Kim, Hyo-Jin;Lee, Hye-Jin;Go, Young-Sam;Roh, Kyung-Hee;Lee, Young-Hwa;Jang, Young-Seok;Suh, Mi-Chung
    • Journal of Plant Biotechnology
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    • v.37 no.3
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    • pp.319-326
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    • 2010
  • An interest in the production of seed-oil based fuel and raw materials, which comes from renewable plant sources, has been intrigued by the phenomenon of global warming and shortage of fossil fuels. Rapeseed (Brassica napus) is the most important oilseed crop, which produces seeds with 40% oil. It is desirable to develop genetically modified rapeseed producing oils, which can be easily converted to biodiesel. As an initial step for development of genetically modified rapeseed for the production of biofuels or bio-based materials, Korean rapeseed cultivars, Naehan, Youngsan, Tammi and Halla, were analyzed. Four Korean rapeseed cultivars produce 32 to 40% oil of seed dry weight, which is rich in oleic acid (more than 60 mole%). The cotyledonary petioles of rapeseed cultivar, Halla, were transformed using Agrobacterium tumefaciens strain GV3101, carrying the uidA gene encoding $\beta$-glucuronidase (GUS) as a reporter gene and the phosphinothricin acetyltransferase (PAT) gene as a selectable marker. The stable integration of PAT gene in the genome of transgenic rapeseeds was confirmed by PCR analysis. Expression of uidA gene in various rapeseed organs was determined by fluorometric assay and histochemical staining. Transformation efficiency of a Korean rapeseed Halla cultivar was 10.4%. Genetic inheritance of transgenes was confirmed in $T_2$ generation.

The Inhibitory Mechanism of Aloe Glycoprotein (NY945) on the Mediator Release in the Guinea Pig Lung Mast Cell Activated with Antigen-Antibody Complexes

  • Ro, Jai-Youl;Lee, Byung-Chul;Chung, Myung-Hee;Lee, Seung-Ki;Sung, Chung-Ki;Kim, Kyung-Hwan;Park, Young-In
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.119-131
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    • 1998
  • It has been reported that the glycoprotein extracted from Aloe has strong anti-inflammatory response. However, there has been no research report yet about the effect of Aloe on allergic hypersensitivity reactivity. By using guinea pig lung mast cells, this study aimed to examine the effects of Aloe glycoprotein (NY945) on the mediator releases caused by mast cell activation, and also aimed to assess the effects of NY945 on the mechanism of mediator releases in the mast cell activation. We partially purified mast cell from guinea pig lung tissues by using the enzyme digestion, the rough and the discontinuous density percoll gradient method. Mast cells were sensitized with IgG1 (anti-OA) and challenged with ovalbumin. Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. The phospholipase D activity was assessed by the production of labeled phosphatidylalcohol. The amount of mass 1, 2-diacylglycerol (DAG) was measured by the $[^3H]DAG$ produced when prelabeled with $[^3H]myristic$ acid. The phospholipid methylation was assessed by measuring the incorporation of the $[^3H]methyl$ moiety into phospholipids of cellular membranes. Pretreatment of NY945 (10 ${\mu}g$) significantly decreased histamine and leukotrienes releases during mast cell activation. The decrease of histamine release was stronger than that of leukotriene during mast cell activation. The phospholipase D activity increased by the mast cell activation was decreased by the dose-dependent manner in the pretreatment of NY945. The amount of DAG produced by PLC activity was decreased by NY945 pretreatment. The amount of mass 1, 2-diacylglycerol produced by activation of mast cells was decreased in the pretreatment of NY945. NY945 pretreatment strongly inhibited the incorporation of the $[^3H]methyl$ moiety into phospholipids. The data suggest that NY945 purified from Aloe inhibits in part an increase of 1, 2-diacylglycerol which is produced by activating mast cells with antigen-antibody reactions, which is mediated via phosphatidylcholine-phospholipase D and phosphatidylinositol-phospholipase C systems, and then followed by the inhibition of histamine release. Furthermore, NY945 reduces the production of phosphatidylcholine by inhibiting the methyltransferase I and II, which decreases the conversion of phosphatidylcholine into arachidonic acid and inhibits the production of leukotrienes.

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3,9-Diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$): a Novel Anti-wrinkle Agent for Cosmeceuticals (새로운 주름개선 소재: 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$)의 개발과 화장품 응용)

  • 이범천;이정재;박성민;김철배;심관섭;김진화;이근수;이천일;표형배
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.7-13
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    • 2004
  • As a novel anti-wrinkle agent, 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^{(R)}$) has been synthesized and its anti-aging effects have been investigated. In the present study, to investigate the relationship between aging and Tensolin-F$^{(R)}$, we examined its effect on scavenging activities of radicals and reactive oxygen species (ROS), in vitro inhibition activity of matrix-metalloproteinase (MMP) and expression of UVA-induced MMPs in human dermal fibroblasts (HDF). Tensolin-F$^{(R)}$ was found to show activities of scavenging radicals and ROS with the $IC_{50}$/ values of 0.2 mM and 0.95 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide radicals, respectively, in the xanthine/xanthine oxidase system. Fluorometric assays for the proteolytic activities of MMP-l (collagenase) were performed using fluorescent collagen substrates. Tensolin-F$^{(R)}$ inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 0.025 mM. Also, UVA induced MMP-1 expression was reduced 85% by treatment with Tensolin-F$^{(R)}$ at 0.8 uM, which was reduced dose-dependent manner. The results of clinical study showed that 4.8 mM Tensolin-F$^{(R)}$ treated group reduced wrinkle significantly compared with placebo treated group (P 〈 0.05). Taken together, these result suggest that Tensolin-F$^{(R)}$ act as an anti-wrinkle agent by taking effects to antioxidation and reducing UVA-induced MMP-l production.-l production.

Detoxification and Paralytic Shellfish Poison Profile with Heating, Storage and Treatment of Alkaline in Blue Mussel, Mytilus edulis (알칼리 처리 및 가열, 저장에 따른 진주담치의 마비성 패류독 성분 특성 및 제독)

  • Jang, Jun-Ho;Yun, So-Mi;Lee, Jong-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.2
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    • pp.212-218
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    • 2006
  • Changes of paralytic shellfish poison (PSP) contents, toxicity and toxin composition with pH and storing periods at different temperature in toxic blue mussel, Mytilus edulis, were tested by using fluorometric HPLC method. Toxicity at pH 3 was the highest as 14.1 MU/g $(100\%)$ and showed 12.9 MU/g $(92.1\%)$ at pH 5, 9.0 MU/g $(63.8\%)$ at pH 7, 3.6 MU/g $(25.5\%)$ at pH 9 and 0.8 MU/g $(5.7\%)$ at pH 10 which suggested PSP was unstable at alkaline conditions. The decrease in toxicity during storage days was depend on pH and temperature. The toxicity markedly decreased until during the first S day storage $(19.9\~65.3\%)$ at all pH (3, 5, 7, 9) and temperature (30, 5, $-20^{\circ}C$), but, slightly decreased after then till to 30 days. C group toxin (C1 and C2) was the major components and other toxins such as GTX 1,2,3,4, STX and dcSTX were detected. Among the 8 toxins, GTX1,4, dcSTX and STX were firstly decreased according to the decreasing the toxicity at all processing conditions. The toxicity in blue mussel (14.1 MU/g) were able to remove by heating over 10 minutes at pH higher than 7.

Effects of Ginsenosides on the Mechanism of Histamine Release in the Guinea Pig Lung Mast Cells Activated by Specific Antigen-Antibody Reactions

  • Ro, Jai-Youl;Ahn, Young-Soo;Kim, Kyung-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.4
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    • pp.445-456
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    • 1997
  • We previously reported that some components of ginsenosides decreased mediator releases evoked by the activation of mast cells with specific antigen-antibody reactions. This study aimed to assess the effects of ginsenosides ($Rb_2$, Re) on the mechanism of histamine release in the mast cell activation. We partially purified guinea pig lung mast cells by using enzyme digestion, the rough and the discontinuous percoll density gradient method. Mast cells were sensitized with $IgG_1$ and challenged with ovalbumin (OA). Histamine was assayed by fluorometric analyzer, leukotrienes by radioimmunoassay. Phospholipase D (PLD) activity was assessed more directly by the production of $[^3H]phosphatidylbutanol$ (PBut) which was produced by PLD-mediated transphosphatidylation in the presence of butanol. The amount of 1,2- diacylglycerol (DAG) were measured by the $[^3H]DAG$ labeled with $[^3H]palmitic$ acid or $[^3H]myristic$ acid. Pretreatment of $Rb_2$ ($300\;{\mu}g$) significantly decreased histamine release by 60%, but Re ($300\;{\mu}g$) increased histamine release by 34%. Leukotrienes release in $Rb_2$ was decreased by 40%, Re was not affected in the leukotrienes release during mast cell activations. An increasing PLD activity during mast cell activation was decreased by the dose-dependent manner in the pretreatment of $Rb_2$, but Re pretreatment facilitated the increased PLD activity during mast cell activation. The amount of DAG produced by phospholipase C (PLC) activity was decreased by $Rb_2$ pretreatment, but Re pretreatment was not affected. The amount of mass DAG was decreased by $Rb_2$ and Re pretreatment during mast cell activation. The data suggest that $Rb_2$ purified from Korean Red Ginseng Radix inhibits the DAG which is produced by the activation of mast cells with antigen-antibody reactions via both phosphatidylinositide-PLC and phosphatidylcholine-PLD systems, and then followed by the inhibition of histamine release. However, Re increases histamine release by stimulation of DAG production, which is mediated by phosphatidylcholine-PLD system rather than by phosphatidylinositide-PLC system, but inhibits the mass DAG production. Thus, it could be inferred that other mechanisms play a role in the increase of histamine release during mast cell activation.

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