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Youra Lee,Ji Hoon Oh,Kyoung-Ah Kong,Myoung Hee Kim 대한의생명과학회 2012 Biomedical Science Letters Vol.18 No.2
Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in Akt1-/- mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and Akt1-/- MEFs. However, the protein level of Gcn5 was significantly increased in Akt1-/- MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in Akt1-/- MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.
( Youra Kang ),( Sushil Chandra Regmi ),( Mi Yeong Kim ),( Suhrid Banskota ),( Jaya Gautam ),( Dong Hee Kim ),( Jung Ae Kim ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
In the current study, macrolactin compounds, macrolactin A (MA) and 7-0-succinyl macrolactin A (SMA), were investigated for their anti-angiogenic activities and action mechanism. MA and SMA inhibited in vitro and in vivoangiogenesis induced by three differentclasses of pro-angiogenic factors, VEGF, IL-8, and TNF-α. SMA exhibited stronger anti-angiogenic activity than MA, and such anti-MDA-MB-231 human breast cancer cell-inoculated CAM assay showing dose-dependent suppression of tumor growth and tumor-induced angiogenesis. In an in vitro PI3K com-petitive activity assay, SMA induced concentration-depen-dent inhibition of class I PI3K isoforms, p110α, p110β, p110δ, and p110★. In addition, non-receptor tyrosine kinase c-Src, which is involved in the activation of PI3K heterodi-mer, was suppressed by MA and SMA. Correspondingly, MA and SMA significantly inhibited the stimulus-induced phos-phorylation of Akt, mTOR, p70S6K, and ribosomal S6 in human umbilical vein endothelial cells (HUVECs). At the same time, the stimulus-induced production of reactive oxygen species (ROS) and activation of NF-κB were signif-icantly suppressed by MA and SMA. Moreover, the macro-lactins suppressed NF-κB-regulated HSP90 protein expression, which stabilizes phosphorylated Akt and NADPH oxidase. Suppression of NF-κB in macrolactin-treated HUVECs with concurrent inhibition of rS6 indicates that Mas effectively block angiogenesis through down-reg-ulation of genes related to angiogenesis at both transcriptional and translational levels. Taken together, the results demon-strate that anti-angiogenic effect of MA and SMA is mediated through inhibition of PI3K/Akt and NADPH oxidase-derived ROS.NF-ΚB signaling pathways. These results further indi-cate that MA and SMA may be applicable for treatment of various diseases associated with angiogenesis.
( Youra Kang ),( Min A Park ),( Se Woong Heo ),( Su Young Park ),( Keon Wook Kang ),( Pil Hoon Park ),( Jung Ae Kim ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0
BACKGROUND: Chemotherapeutic drug resistance remains a clinical obstacle in cancer management. Drug-resistant cancer cells usually exhibit cross-resistance to ionizing radiation, which has devastating consequences for patients. With a better understanding of the molecular mechanisms, it will be possible to develop strategies to overcome this cross-resistance and to increase therapeutic sensitivity. METHODS: Natural and synthetic flavonoid compounds including xanthohumol, the principal flavonoid in hops, were investigated for its radio-sensitizing activity on human breast cancer MCF-7 and adriamycin-resistant MCF-7 (MCF-7/ADR) cells. Chemo-sensitizing or radio-sensitizing effect was analyzed by tetrazolium-based colorimetric assay and flow cytometry. Western blot analysis, confocal microscopy, gene silencing with siRNA transfection and luciferase reporter gene assay were performed to examine signaling molecule activation. RESULTS: Among the tested flavonoid compounds, pretreatment of the cells with xanthohumolsignificantly sensitized MCF-7/ADR cells to the radiation treatment by inducing apoptosis. In MCF-7/ADR cells, treatment with xanthohumol alone or with gamma-rays significantly decreased levels of anti-apoptotic proteins. Multi-drug resistance 1 (MDR1), epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) expression levels in MCF-7/ADR cells were suppressed by xanthohumol treatment. In addition, xanthohumol treatment increased death receptor (DR)-4 and DR5 expression. The xanthohumol-induced changes of these resistance-related molecules in MCF-7/ADR cells were synergistically increased by gamma-ray treatment. CONCLUSIONS: Xanthohumol restored sensitivity of MCF-7/ADR cells to doxorubicin and radiation therapies. GENERAL SIGNIFICANCE: Our results suggest that xanthohumol may be a potent chemo- and radio-sensitizer, and its actions are mediated through STAT3 and EGFR inhibition.ⓒ2012 Elsevier B. V. All rights reserved.
Proteomic analysis of glutamate-induced toxicity in HT22 cells
Lee, Youra,Park, Hye-won,Park, Sung Goo,Cho, Sayeon,Myung, Pyung Keun,Park, Byoung Chul,Lee, Do Hee WILEY-VCH 2007 Proteomics Vol. No.
<P>In the present study, we have investigated the proteome changes associated with glutamate-induced HT22 cell death, a model system to study oxidative stress-mediated toxicity. Among a number of HT22 proteins exhibiting altered expression, several molecular chaperones demonstrated substantial changes. For example, the levels of Hsp90 and Hsp70 decreased as cell death progressed whereas that of Hsp60 increased dramatically. Interestingly, cytosolic Hsp60 increased more prominently than mitochondrial Hsp60. Concomitantly, the accumulation of poly-ubiquitylated proteins and differential regulation of the peptidase activities and the subunits of 26S proteasomes were observed in glutamate-treated HT22 cells. Our findings that the molecular chaperones and the ubiquitin-proteasome system undergo changes during glutamate-induced HT22 cell death may suggest the importance of a protein quality control system in oxidative damage-mediated toxicity.</P>
허유라(Youra Heo),조익현(Eikhyun Cho),강신일(Shinill Kang) 한국생산제조학회 2011 한국생산제조시스템학회 학술발표대회 논문집 Vol.2011 No.4
Guided mode resonance protein chips are capable of high sensitivity in the detection of molecular interactions, by measuring the movement of sharp transmittance peak. We designed a guided mode resonance protein chip by computer simulation based on rigorous coupled wave analysis, and created a prototype by UV nano imprinting. We also demonstrated the use of the guided mode resonance protein chip as a protein sensor by verifying the formation of peak wavelength value and the shift of the peak due to biotin and streptavidin interactions.
Lee, Youra,Lee, Do Hee,Kho, Chang Won,Lee, Ah Young,Jang, Mi,Cho, Sayeon,Lee, Choong Hwan,Lee, Jong Suk,Myung, Pyung Keun,Park, Byoung Chul,Park, Sung Goo Elsevier 2005 FEBS letters Vol.579 No.21
<P><B>Abstract</B></P><P>Purine catabolic pathway in <I>Bacillus subtilis</I> is consisted of more than 14 genes. Among these genes, <I>pucL</I> and <I>pucM</I> are required for uricase activity. While PucL is known to encode the uricase itself, the function of PucM is still unclear although this protein is also indispensable for uric acid decomposition. Here, we provide evidence that PucM, a transthyretin-related protein, functions to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Based on these results, we propose that transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as a hydroxyisourate hydrolase.</P>
영어 -ly 유형 인식견지부사의 담화표지 기능 이해도 분석: 한국인 EFL 학습자와 원어민 화자를 대상으로
이유라(Youra Lee),유석훈(Seok-Hoon You) 서울대학교 언어교육원 2020 語學硏究 Vol.56 No.3
English -ly adverbials (LY) with epistemic modality are frequently used as discourse markers (DM) in spoken language. In this paper, LY DM is defined as an epistemic stance marker. The experiment for this study aims to analyze Korean EFL learners" comprehension of LY used as a DM on the basis of the hypothesis that they would perceive LY differently from how English native speakers perceive them. In order to conduct the experiment, previous studies on DMs were thoroughly examined to establish the theoretical framework. Based on the framework, the Discourse Marker Interpretation Test (DMIT) was designed. The research data collected through the test were analyzed using quantitative methods. Additionally, interviews were conducted to supplement the interpretation of the research results. The experiment mainly determined that, unlike English native speakers, who properly interpreted LY with their DM function, Korean EFL learners are inclined to interpret LY used as DMs simply with their lexical meanings (the dictionary definition). Results suggest that there is a high possibility for Korean EFL learners to commit more errors when encountering LY DMs.