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.

hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb α via IRES-mediated translation

Kim, Do-Yeon,Woo, Kyung-Chul,Lee, Kyung-Ha,Kim, Tae-Don,Kim, Kyong-Tai Oxford University Press 2010 Nucleic acids research Vol.38 No.20

<P>The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb α functions as a transcriptional repressor, affecting expression patterns of other clock genes. For the continuous and robust oscillation of the molecular clock system, the levels of Rev-erb α protein are expected to be tightly regulated with the correct timing. Here, we demonstrate that Rev-erb α has an internal ribosomal entry site (IRES) in its 5′ untranslated region. Furthermore, we demonstrate that heterogeneous nuclear ribonucleoprotein Q and polypyrimidine tract-binding protein (PTB) modulate the IRES-mediated translation of Rev-erb α. We suggest that the rhythmic binding affinity of hnRNP Q to the Rev-erb α IRES and the change in PTB cytosolic levels lead to maintenance of the oscillation profile of the Rev-erb α protein.</P>

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

Reaction-based two-photon probes for <i>in vitro</i> analysis and cellular imaging of monoamine oxidase activity

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>

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>

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>

Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25

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>

Nonthermal-plasma-mediated animal cell death

Kim, Wanil,Woo, Kyung-Chul,Kim, Gyoo-Cheon,Kim, Kyong-Tai Institute of Physics [etc.] 2011 Journal of Physics. D, Applied Physics Vol.44 No.1

<P>Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells <I>in vivo</I>. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.</P>

hnRNP Q mediates a phase-dependent translation-coupled mRNA decay of mouse <i>Period3</i>

Kim, Do-Yeon,Kwak, Eunyee,Kim, Sung-Hoon,Lee, Kyung-Ha,Woo, Kyung-Chul,Kim, Kyong-Tai Oxford University Press 2011 Nucleic acids research Vol.39 No.20

<P>Daily mRNA oscillations of circadian clock genes largely depend on transcriptional regulation. However, several lines of evidence highlight the critical role of post-transcriptional regulation in the oscillations of circadian mRNA oscillations. Clearly, variations in the mRNA decay rate lead to changes in the cycling profiles. However, the mechanisms controlling the mRNA stability of clock genes are not fully understood. Here we demonstrate that the turnover rate of mouse <I>Period3</I> (m<I>Per3</I>) mRNA is dramatically changed in a circadian phase-dependent manner. Furthermore, the circadian regulation of m<I>Per3</I> mRNA stability requires the cooperative function of 5′- and 3′-untranslated regions (UTRs). Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) binds to both 5′- and 3′-UTR and triggers enhancement of translation and acceleration of mRNA decay. We propose the phase-dependent translation coupled mRNA decay mediated by hnRNP Q as a new regulatory mechanism of the rhythmically regulated decay of m<I>Per3</I> mRNA.</P>