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백서의 우울모형에서의 칼슘통로 길항제 에타베린(Ethaverine)의 항우울효과
이상경,김선희,김록우,윤성환,김용관,김경태,김영훈 대한신경정신의학회 2000 신경정신의학 Vol.39 No.2
연구목적: 본 전임상연구에서는 우울증의 두가지 동물모형을 통해 에타베린이 단독 혹은 이미프라민과 병용처치 되었을 때의 효과를 알아보고자 하였다. 방법: 표준화된 검사법인 강제수영검사를 사용하여 옹성백서에게 에타베린(20mg/kg) 및 이미프라민 (20mg/kg)을 단독 혹은 병용 처치하였을 때의 부동시간의 변화를 관찰하였고, 경도의 만성 스트레스를 3주간 가한 후 4주간 에타베린과 이미프라민을 단독 혹은 병용 처치하였을때의 자당섭취량의 변화를 관찰하였다. 결과: 약물을 1회 단기처치 및 7일간 장기처치한 강제수영검사에서 이미프라민 및 에타베린 단독처치는 대조군에 비하여 부동시간의 단축을 보였고 에타베린은 이미프라민의 부동시간 감소에 대한 증강작용을보였다. 경도의 만성스트레스 실험에서도 3주간의 스트레스로 인하여 감소된 백서의 자당섭취량을 이미 프라민 및 에타베린이 회복시켰으며, 치료초기에 두 약물의 병용처치효과가 두드러졌다. 결론: 본 연구의 결과는 에타베린이 향우울 효과를 가지고 있음을 시사하며, 삼환계 항우울제인 이미프라민의 항우울효과를 증강시키므로 에타베린의 임상적 활용 가능성을 보여준다. Objectives: This pre-clinical study was performed to assess the effects of ethaverine in the two kinds of behavioral models of depression in rats. Methods: We observed the changes of the immobility time in the froced swimming test and the quantity of sucrose consumed in the chronic mild stress model, using ethaverine(20mg/kg) alone, imipramine(20mg/kg) alone, or ethaverine and imipramine concomitantly. Results: In the forced swimming test, both single treatment and chronic treatment(for 7days) with imipramine or ethaverine significantly reduced the immobility time, and concomitant chronic treatment with ethaverine potentiated the effect of imipramine. In the chronic mild stress model, both imipramine and ethaverine reversed the decreased sucrose consumption induced by 3-week stress and concomitantly treated ethaverine potentiated the effect of imi-pramine in the early phase of treatment. Conclusions: The data suggest that ethaverine can be used alone or concomitantly with other antidepressants in the clinical situation.
Compocasting 법으로 제조된 AS91D/SiC_p composite 의 특성 평가
이경태,김세광,김영직 成均館大學校 科學技術硏究所 1994 論文集 Vol.45 No.2
The properties of SiC particle reinforced metal matrix composites(MMCs) of magnesuim alloy were investigated. MMCs was produced by compocasting method and specimens were fabricated by pressing of slurry. These specimens were evaluated in tensile strength, hardness, wear resistance, oxidation properties. The hardness and tensile strength were increased with SiC_p contents. Up to 5 % addition of SiC_p the wear resistancewas improved. It was deteriorated however above 5 % addition because of adhesive wear. Under isothermal oxidation conditions, oxidation resistance was improved with SiC_p.
Kim, Seong-Hoon,Lyu, Ha-Na,Kim, Ye Seul,Jeon, Yong Hyun,Kim, Wanil,Kim, Sangjune,Lim, Jong-Kwan,Lee, Ho Won,Baek, Nam-In,Choi, Kwan-Yong,Lee, Jaetae,Kim, Kyong-Tai American Society for Pharmacology and Experimental 2015 The Journal of Pharmacology and Experimental Thera Vol.352 No.1
<P>To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrier-to-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.</P>
Dendritic planarity of Purkinje cells is independent of Reelin signaling
Kim, Jinkyung,Park, Tae-Ju,Kwon, Namseop,Lee, Dongmyeong,Kim, Seunghwan,Kohmura, Yoshiki,Ishikawa, Tetsuya,Kim, Kyong-Tai,Curran, Tom,Je, Jung Ho Springer Berlin Heidelberg 2015 BRAIN STRUCTURE AND FUNCTION Vol.220 No.4
<P>The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly delineated. Here, we use synchrotron X-ray microscopy to obtain 3-D images of Golgi-stained Purkinje cell dendrites. Purkinje cells that failed to migrate completely exhibited conical dendrites with abnormal 3-D arborization and reduced dendritic complexity. Furthermore, their spines were fewer in number with a distorted morphology. In contrast, Purkinje cells that migrated successfully displayed planar dendritic and spine morphologies similar to normal cells, despite reduced dendritic complexity. These results indicate that, during cerebellar formation, Purkinje cells migrate into an environment that supports development of dendritic planarity and spine formation. While Reelin signaling is important for the migration process, it does not make a direct major contribution to dendrite formation.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00429-014-0780-2) contains supplementary material, which is available to authorized users.</P>
Kim, Sangjune,Park, Do-Young,Lee, Dohyun,Kim, Wanil,Jeong, Young-Hun,Lee, Juhyun,Chung, Sung-Kee,Ha, Hyunjung,Choi, Bo-Hwa,Kim, Kyong-Tai American Society for Microbiology 2014 Molecular and cellular biology Vol.34 No.4
<P>Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC <I>in vitro</I>. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.</P>
Kim, Sangjune,Lee, Dohyun,Lee, Juhyun,Song, Haengjin,Kim, Hyo-Jin,Kim, Kyong-Tai American Society for Microbiology 2015 Molecular and cellular biology Vol.35 No.10
<P>Molecular chaperones monitor the proper folding of misfolded proteins and function as the first line of defense against mutant protein aggregation in neurodegenerative diseases. The eukaryotic chaperonin TRiC is a potent suppressor of mutant protein aggregation and toxicity in early stages of disease progression. Elucidation of TRiC functional regulation will enable us to better understand the pathological mechanisms of neurodegeneration. We have previously shown that vaccinia-related kinase 2 (VRK2) downregulates TRiC protein levels through the ubiquitin-proteasome system by recruiting the E3 ligase COP1. However, although VRK2 activity was necessary in TRiC downregulation, the phosphorylated substrate was not determined. Here, we report that USP25 is a novel TRiC interacting protein that is also phosphorylated by VRK2. USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated the Thr<SUP>680</SUP>, Thr<SUP>727</SUP>, and Ser<SUP>745</SUP> residues. Impaired USP25 deubiquitinating activity after VRK2-mediated phosphorylation may be a critical pathway in TRiC protein destabilization.</P>
Obtusilactone B from Machilus Thunbergii targets barrier-to-autointegration factor to treat cancer.
Kim, Wanil,Lyu, Ha-Na,Kwon, Hyun-Sook,Kim, Ye Seul,Lee, Kyung-Ha,Kim, Do-Yeon,Chakraborty, Goutam,Choi, Kwan Yong,Yoon, Ho Sup,Kim, Kyong-Tai American Society for Pharmacology and Experimental 2013 Molecular pharmacology Vol.83 No.2
<P>Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer. Obtusilactone B is a butanolide derivative purified from Machilus thunbergii. In this study, we show that obtusilactone B functions as a small-molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)-mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is important in maintaining lamin integrity, which is closely associated with diseases that include cancer. Specific binding of obtusilactone B to BAF suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment.</P>
Potentiation of antidepressant effect of imipramine by repeated treatment with ethaverine
Kim, Sun-Hee,Kim, Young-Hoon,Lee, Sang-Kyeong,Kim, Jae-Hong,Kim, Kyong-Tai 대한생물치료정신의학회 1996 생물치료정신의학 Vol.2 No.2
Daily treatment for 10 days with 20㎎/㎏ imipramine and 10㎎/㎏ ethaverine reduced the immobilization time in the behavioral despair test in rats. However, 10㎎/㎏ verapamil did not reduce it significantly. It was suggested that ethaverine concomitantly administered potentiated the long-term effect of imipramine on the reduction of the immobilization time. In a hall of those rats(3/6) which had been repeatedly treated with both 20㎎/㎏ imipramine and 10㎎/㎏ ethaverine, vigorous swimming was observed during most of the test time despite no increased motor activity in an open field observation. In a second experiment, ethaverine exhibited the tendency of dose-dependent reduction of the immobilization time. In conclusion the data suggest that ethaverine has a anti-immobility effect in the behavioral despair test in rats and that it can be useful in potentiating the antidepressant effect of imipramine clinically.
Macro Histone H2A1.2 (MacroH2A1) Protein Suppresses Mitotic Kinase VRK1 during Interphase
Kim, Wanil,Chakraborty, Goutam,Kim, Sangjune,Shin, Joon,Park, Choon-Ho,Jeong, Min-Woo,Bharatham, Nagakumar,Yoon, Ho Sup,Kim, Kyong-Tai American Society for Biochemistry and Molecular Bi 2012 The Journal of biological chemistry Vol.287 No.8
Kim, Dokyoung,Sambasivan, Sunderraman,Nam, Hyoseok,Hean Kim, Ki,Yong Kim, Jin,Joo, Taiha,Lee, Kyung-Ha,Kim, Kyong-Tai,Han Ahn, Kyo The Royal Society of Chemistry 2012 Chemical communications Vol.48 No.54
<P>Reaction-based fluorescent probes for monoamine oxidases A and B are developed based on a new two-photon absorbing compound and its precursor. The probes show turn-on fluorescence response to the enzymes owing to the two-photon absorbing compound produced by the enzymatic activity, as monitored by one- as well as two-photon microscopy for the first time.</P> <P>Graphic Abstract</P><P>Reaction-based fluorescent probes for monoamine oxidases A and B are developed based on a new two-photon absorbing compound and its precursor. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2cc32424e'> </P>