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        2,4-Bis(4-hydroxybenzyl)phenol Inhibits Heat Shock Transcription Factor 1 and Sensitizes Lung Cancer Cells to Conventional Anticancer Modalities

        Yoon, Taesook,Kang, Ga-Young,Han, Ah-Reum,Seo, Eun-Kyoung,Lee, Yun-Sil American Chemical Society and American Society of 2014 Journal of natural products Vol.77 No.5

        <P>Heat shock factor 1 (HSF1) is a transcription factor that regulates expression of heat shock protein (HSP) genes in response to stress. HSPs are expressed at high levels in a wide range of tumors. It has been reported that HSF1 and HSPs are associated closely in tumorigenesis. In the present study, a screen was performed using a luciferase reporter under the control of a heat shock element to find inhibitors of HSF1 activity, and 2,4-bis(4-hydroxybenzyl)phenol (<B>1</B>), isolated from the rhizomes of <I>Gastrodia elata</I>, was identified as an active compound. This substance effectively inhibited HSF1 activity and decreased levels of HSP27 and HSP70. Compound <B>1</B> induced the degradation of HSF1 protein through dephosphorylation of HSF1 on S326, which decreases HSF1 protein stability. In addition, <B>1</B> also induced growth arrest and apoptosis of NCI-H460 human lung cancer cells. Markers of apoptosis, such as cleaved PARP and cleaved caspase-3, were detected after treatment with <B>1</B>. Furthermore, cotreatment with <B>1</B> and conventional anticancer modalities such as paclitaxel, cisplatin, or ionizing radiation potentiated their effects on lung cancer cells. These results suggest that inhibition of HSF1 by <B>1</B> may help overcome resistance to conventional anticancer modalities in HSF1-overexpressed cancer cells.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2014/jnprdf.2014.77.issue-5/np4009333/production/images/medium/np-2013-009333_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np4009333'>ACS Electronic Supporting Info</A></P>

      • Identification of the Self-Interaction of Rat TCTP/lgE-Dependent Histamine-Releasing Factor Using Yeast Two-Hybrid System

        Yoon, Taesook,Jung, Jaehoon,Kim, Minjeong,Lee, Kang Man,Choi, Eung Chil,Lee, Kyunglim 梨花女子大學校 藥學硏究所 2000 藥學硏究論文集 Vol.- No.9

        To further understand the biological function of translationally controlled tumor protein (TCTP), also known as IgE-dependent histamine-releasing factor (HRF), the yeast two-hybrid system was used to screen interacting molecules. We isolated cDNA clones coding for TCTP/HRF, suggesting that it may have a self-interacting property. Domain mapping of the interaction revealed that the C-terminal region of residue 126-172 is involved in self-interaction. The self-interacting property of TCTP/HRF was further supported by FPLC gel-filtration chromatography and coimmunoprecipitation analysis from transfected COS-7 cells. Our data suggests that TCTP/HRF may have a potential to self-interact through the C-terminal region, and the self-interaction property may be related to its biological function.

      • Pharmacological activities of Glehnia littoralis

        Yoon Taesook,Choo Byungkil,Cheon Myeoungsook,Lee Doyeon,Choi Goya,Chae sungwook,Lee Ayeong,Kim Hokyoung 한국한의학연구원 2008 한국한의학연구원논문집 Vol.14 No.1

        Glehnia littoralis (Umbelliterae), a perennial herb distributed along the coastline of northern Pacific countries, is the medicinal plant used traditionally for treatment of various diseases. This review focuses on the various pharmacological activities of Glehnia littoralis for understanding about its traditional medicinal applications, medicinal uses in the modem society, and potentials for drug development. Glehnia littoralis was reported to have anti-oxidant, anti-tumor, anti-amnesic, blood circulation-promoting, immunomodulatory, anti-microbial, and allelopathic activities. However, their mechanisms remain to be clarified. Because Glehnia littoralis has been prescribed in traditional Oriental medicine as a tonic herb, Glehnia littoralis can be better than other chemical drugs and medicines which exert the equal pharmacological activities. Although the activities of Glehnia littoralis are not specifically high-potent with unique mode of action, it may turn out that it can be beneficial to exert multiple pharmacological activities. In view of low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of Glehnia littoralis, it needs to be prudent to evaluate its properties and applications further.

      • KCI등재
      • The Effects of Glehnia littoralis on the Inflammatory mediators in Mouse Macrophage Cells

        Yoon Taesook,Cheon Myeongsook,Lee A-Yeong,Choi Goya,Kim Seungju,Moon Byeongcheol,Choo Byungkil,Kim Hokyoung 한국한의학연구원 2008 한국한의학연구원논문집 Vol.14 No.3

        Glennie littoralis (Umbelliferae) is the medicinal plant used traditionally for treatment of immune-related diseases. Prostaglandins and nitric oxide (NO) have been implicated as important mediators in the processes of inflammation and carcinogenesis. For understanding the mechanisms for pharmacological activities of Glehnia littoralis, we evaluated the inhibitory activity of Glehnia littoralis on lipopolysaccharide (LPS)-induced prostaglandin E₂ (PGE2) and NO production in mouse macrophage RAW264.7 cells. The results showed that the extract of Glehnia littoralis inhibited LPS-induced PGE₂ production effectively, but not NO. Additional study revealed that the extract of Glehnia littoralis suppressed cyclooxygenase-2 (COX-2) expression in a dose-dependent manner. Present study suggests that Clehnia Iittorslis may have anti-inflammatory and/or cancer chemopreventive activity through the inhibition of PGE₂ production by the suppression of COX-2 activity.

      • Inhibition of Na,K-ATPase-suppressive activity of translationally controlled tumor protein by sorting nexin 6

        Yoon, Taesook,Kim, Moonhee,Lee, Kyunglim Elsevier 2006 FEBS letters Vol.580 No.14

        <P><B>Abstract</B></P><P>Translationally controlled tumor protein (TCTP) has both extra- and intracellular functions. Our group recently reported that TCTP interacts with Na,K-ATPase and suppresses its activity. Our studies led to the identification of sorting nexin 6 (SNX6) which binds with TCTP as a potential negative regulator of TCTP. SNX6 does not interact directly with any cytoplasmic domains of Na,K-ATPase. However, when overexpressed, it restores the Na,K-ATPase activity suppressed by TCTP. This was confirmed by measurements of purified plasma membrane Na,K-ATPase activity after incubation with recombinant TCTP and SNX6. SNX6 alone has no effect on Na,K-ATPase activity, but activates Na,K-ATPase via inhibition of TCTP. Inhibition of endogenous TCTP by the overexpression of SNX6 or knockdown of TCTP expression by siTCTP increased Na,K-ATPase activity above the basal level. The interaction between SNX6 and TCTP thus appears to regulate Na,K-ATPase activity.</P>

      • The Antiobesity Effect of <i>Polygonum aviculare</i> L. Ethanol Extract in High-Fat Diet-Induced Obese Mice

        Sung, Yoon-Young,Yoon, Taesook,Yang, Won-Kyung,Kim, Seung Ju,Kim, Dong-Seon,Kim, Ho Kyoung Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

        <P>The antiobesity effects of a <I>P. aviculare</I> ethanol extract (PAE) in high-fat diet- (HFD-) induced obese mice were investigated. The mice were fed an HFD or an HFD supplemented with PAE (400 mg/kg/day) for 6.5 weeks. The increased body weights, adipose tissue weight, and adipocyte area as well as serum total triglyceride, leptin, and malondialdehyde concentrations were decreased in PAE-treated HFD-induced obese mice relative to the same measurements in untreated obese mice. Furthermore, PAE significantly suppressed the elevated mRNA expression levels of sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor <I><I>γ</I></I>, fatty acid synthase, and adipocyte protein 2 in the white adipose tissue of obese mice. In addition, PAE treatment of 3T3-L1 cells inhibited adipocyte differentiation and fat accumulation in a dose-dependent manner. These results suggest that PAE exerts antiobesity effects in HFD-induced obese mice through the suppression of lipogenesis in adipose tissue and increased antioxidant activity.</P>

      • Anti-obesity effects of Actinidia polygama extract in mice with high-fat diet-induced obesity

        SUNG, YOON-YOUNG,YOON, TAESOOK,YANG, WON-KYUNG,MOON, BYEONG-CHEOL,KIM, HO KYOUNG Spandidos Publications 2013 MOLECULAR MEDICINE REPORTS Vol.7 No.2

        <P>Actinidia polygama has been used as a herbal folk medicine for treating pain, gout, rheumatoid arthritis and inflammation. In the present study, the anti?obesity properties of Actinidia polygama extract (APE) were investigated in mice with high?fat diet?induced obesity. APE treatment of high?fat diet (HFD)?fed obese mice significantly reduced body weight, adipose tissue mass and serum triglyceride and leptin levels relative to the HFD?fed mice. Food intake did not differ between the HFD and HFD+APE groups, although the food efficiency ratio (FER) was significantly decreased in the HFD+APE group compared with the HFD group. Histological examination showed that the sizes of the adipocytes were significantly smaller in the HFD+APE group compared with the HFD group. Serum levels of aspartate transaminase were significantly decreased in the HFD+APE mice compared with the HFD?fed mice, but serum levels of alanine transaminase (ALT), blood urea nitrogen and creatinine were not significantly changed in the HFD+APE mice compared with the levels in the normal diet (ND)?fed and HFD?fed mice. These results suggest that APE may be useful for treating metabolic diseases, including obesity and hyperlipidemia, without toxic side?effects.</P>

      • Interaction of Cofilin with Triose-phosphate Isomerase Contributes Glycolytic Fuel for Na,K-ATPase via Rho-mediated Signaling Pathway

        Jung, Jaehoon,Yoon, Taesook,Choi, Eung Chil,Lee, Kyunglim 梨花女子大學校 藥學硏究所 2002 藥學硏究論文集 Vol.- No.11

        We reported previously that cofilin, an actin-bindingprotein, interacts with Na,K-ATPase and enhances itsactivity (Lee, K., Jung, J., Kim, M., and Guidotti,G.(2001) Biochem.J. 353,377-385). To understand the na-ture of this interaction and the role of cofilin in theregulation of Na,K-ATPase activity, we searched for co-filin-binding proteins in the rat skeletal muscle cDNAlibrary using the yeast two-hybrid system. Several cDNAclones were isolated, some of which coded for triose-phosphate isomerase, a glycolytic ensyme. The interac-tion of cofilin with triose-phosphate isomerase as well asNa,K-ATPase was confirmed by immunoprecipitationand confocal microscopy in HeLa cells. Cofilin wastranslocated to the plasma membrane along with triose-phosphate isomerase by the Rho activator Iysophospha-tidic acid but not by the pl60 Rhe-associated kinaseinhibitor Y-27632, suggesting that the phosphorylatedform of cofilin bound to TPI interacts with Na,K-ATPase.Ouabain-sensitive ^86Rb^+ uptake showed that Na,K-ATPase activity was increaged by the overexpression ofcofilin and Iysophosphatidic acid treatment, but not bythe overexpression of mutant cofilia S3A and Y-27632treatment. Pretreatment with the glycolytic inhibitoriodoacetic acid caused a remarkable reduction of Na,K-ATPase activity, whereas pretreatment with the oxida-tive inhibitor carbonyl cyanide m-chlorophenylhydra-zone caused no detectable changes, suggesting that thephosphorylated cofilin is involved in feeding glycolyticfuel for Na,K-ATPase activity. These findings provide anovel molecular mechanism for the regulation of Na,K-ATPase activity and for the nature of the functionalcoupling of cellular energy transduction.

      • 한의학 고문헌의 단방용례 분석을 통한 천문동의 기대효능 연구

        최고야(Choi Goya),윤태숙(Yoon Taesook),추병길(Choo Byungkil),문병철(Moon Byeongcheol),채성욱(Chae Sungwook),김호경(Kim Hokyoung) 한국한의학연구원 2008 한국한의학연구원논문집 Vol.14 No.1

        We referred to twenty-two Korean medicinal literatures for application of a single-medicine prescription using Asparagi Tuber(Asparagus cochinchinensis) to form the groundwork for scientific modernization of Korean medicine. Our study revealed the following. 1. Principle expectant effects of Asparagi Tuber were prolong life; elevation of stamina or activity; improvement of asthenia; remedy of epilepsy, mental disease or convulsions; relief of xerosis; treatment of tumor, abscess or intumescence; extermination of endoparasite; solution of numbness, etc. 2. The records show that 95% of directions are per oral. 3. 38% of the cases, Asparagi Tuber was used without its jacket or core. 4. Alcohol and honey were generally used as solvent and additive. We suggest to perform the further studies for the scientific verification of the expectant effects of Asparagi Tuber and its different efficacy by processing, solvent and additives.

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