Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

Yoo, Jung-Yoon,Choi, Kyung-Chul,Kang, HeeBum,Kim, Young Jun,Lee, Jeongmin,Jun, Woo Jin,Kim, Mi-Jeong,Lee, Yoo-Hyun,Lee, Ok-Hee,Yoon, Ho-Geun Elsevier 2010 FEBS letters Vol.584 No.11

<P><B>Abstract</B></P><P>This is the first report that L(3)mbt-like 2 (L3MBTL2) specifically interacts with the histone deacetylase domain of histone deacetylase 3 (HDAC3) via its MBT domain. Here, we show that L3MBTL2 selectively interacts with HDAC3, but not other class I HDACs. An in vitro peptide-binding assay demonstrated the specific association of HDAC3 with methylated histone-K20 tail and L3MBTL2. Furthermore, depletion of HDAC3 resulted in a decrease of methylated K20-H4, as well as an increase in acetylated histone H3. Consequently, HDAC3 knock-down selectively suppressed L3MBTL2-mediated transcriptional repression. Taken together, our results reveal the concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression.</P><P><B>Structured summary</B></P><P>MINT-7719975: <I>L3MBTL2</I> (uniprotkb:Q969R5) and <I>HDAC3</I> (uniprotkb:O15379) <I>colocalize</I> (MI:0403) by <I>fluorescence microscopy</I> (MI:0416)</P><P>MINT-7719941, MINT-7719921: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>binds</I> (MI:0407) to <I>HDAC3</I> (uniprotkb:O15379) by <I>pull down</I> (MI:0096)</P><P>MINT-7719991: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>anti bait coimmunoprecipitation</I> (MI:0006)</P><P>MINT-7719958: <I>L3MBTL2</I> (uniprotkb:Q969R5) <I>physically interacts</I> (MI:0915) with <I>HDAC3</I> (uniprotkb:O15379) by <I>anti tag coimmunoprecipitation</I> (MI:0007)</P><P>MINT-7719897: <I>HDAC3</I> (uniprotkb:O15379) <I>physically interacts</I> (MI:0915) with <I>L3MBTL2</I> (uniprotkb:Q969R5) by <I>two hybrid</I> (MI:0018)</P>

새로운 Acetylcholinesterase inhibitors의 합성

최순규,김형민,조승환,최학기,박유미,이용균,정대일,김인식,한정태 동아대학교 부설 기초과학연구소 2004 基礎科學硏究論文集 Vol.21 No.1

노인성 치매의 일종인 alzheimer's disease의 효과적인 억제제를 합성하기 위해 우리는 분자 모델링에 의한 가장 적합한 물질인 m-[(N,N,N-trimethylammonio)phenyl]boronic acid를 합성하였다. 출발물질인 3-aminophenylboronic acid monohydrate의 경우 boronic acid의 작용기인 hydroxyl group을 protecting시킴으로써 반응의 안정성을 기하였다. Quarternary ammonium salt는 과량의 methyliodide와 염기 촉매인 potassium hydrogen carbonate를 사용하여 용매인 methanol에서 반응시켜 상당히 높은 수율을 얻을 수 있었다. 또한 과량의 methyliodide와 염기촉매인 potassium hydrogen carbonate를 사용하여 용매인 methanol에서 반응시킨 결과 boronic acid의 protection없이도 안정하게 반응이 진행되어짐을 확인할 수 있었다. In order to syntheisize a effective inhibotor for alzheimer's disease, we synthesized m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4 which is designed by molecular modeling form. We protected the hydroxyl group of 3-aminophenylboronic acid monohydrate 1 with ethlyne glycol to remove the reactivity if hydroxyl group. To synthesize m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4, we reacted 3-aminophenylboronic acid monohydrate 1 with ezcess methyl iodide and potassium hydrogen carbonate as a base-catalyst in methanol. but On executed reaction without protection on hydroxyl group, we found out the result that the hydroxyl group of boronic acid group at 3-aminophenylboronic acid monohydrate 1 didn't react with excess methyliodide. Synthesized m-[(N,N,N-trimethylammonio)phenyl]boronic acid 4 is in progress about biological tests as a plausible acetylcholinesterase inhibitor.

농촌지역 노인들의 우울증상에 관련된 요인들의 특성

송미숙,전기홍,송현종,김정은,박승구,신상건,이동훈,정성현,최연주,최완철,최민규,황재철,홍지만 아주대학교 1997 아주의학 Vol.2 No.2

This study was performed to identify risk factors for depression among the elderly in a rural area. A survey was done for the elderly living in Gosam-myenn, Ansung-kun during the period of July 28, 1997 and July 30, 1997. Demographic and sodoeconornic characteristics, and functional and health Status were assessed using a structured questionnaire, and the level of depression was measured by GDS score. The data obtained were analyzed by frequencies, percentage, t-test, ANOVA, and multiple regression, and the results were as follows: 1. The total sample consisted of 133 elderly. Of them, 47 elderly (35.4%) showed significant depressive Symptoms. 2. The GDS score was the highest for the group over 85 years of age (p < 0.05). Those living alone or widowed showed lower GDS score than those living with someone or married (p < 0.05). 3. The GDS score was the highest in the absolutely dependent group, followed by the partially dependent group, and the independent group (p < 0.01). The elderly who perceived their health Status as excellent showed the lowest GDS score. In contrast, those who had more than five chronic diseases showed the highest GDS score. 4. The elderly receiving financial and emotional support from their family or friends showed lower GDS score compared to those without any support. 5. The economically dependent group showed higher GDS score than that of independent group. 6. The elderly who involved in leisure activities showed lower GDS score than those without any involvement. 7. In terms of risk factors for depression, we found that perceived health Status, subjective economic Status, leisure activities, living arrangement and financial support were inversely associated with GDS score, whereas labor support was positively associated with GDS score. Based upon the above findings, this study suggests that these risk factors for depression in the elderly should be taken into consideration for a comprehensive mental health program for the elderly living in the rural area.

당 첨가량에 따른 송이정과의 물성 및 관능 특성

박미란 ( Mi Lan Park ),최수근 ( Soo Keun Choi ),정인창 ( In Chang Jung ),변광인 ( Gwang In Byun ) 한국식생활문화학회 2006 韓國食生活文化學會誌 Vol.21 No.6

한국비서자격시험의 개선점과 비교연구

남자현,이미정,이미영,이아영,정해금,최유정,이미숙,전인선,정혜림 이화여자대학교 법정대학 비서학과 1997 비서학연구 Vol.- No.17

우리나라 일부 석면사업장의 석면폐 유병률

백도명,백남원,최정근,손미아,임정기,이원진,문영한,박정선,최병순 大韓産業醫學會 1995 대한직업환경의학회지 Vol.7 No.1

Asbestos industry has been in operation over 60 years in Korea. However, the prevalence of asbestosis has not been yet reported. With rapid turn-over of workers, previous cross-sectional studies of current workers on the job could not find cases with exposures long enough for the development of asbestosis. This study was done to evaluate asbestosis prevalence of those worksites with operation history of more than 20 years. In total, 139 workers from 5 worksites were examined. Asbestos industries covered in the study include 2 asbestos textile, 1 brake lining, and 2 ship repairing worksites. Chest x-ray was taken from all workers and read by two experts familiar with pneumoconiosis classification according to 1980 ILO guidelines. Those with findings compatible with asbestosis were further ckecked with high resolution computerized tomography (HRCT). Pulmonary function tests were done according to ATS guidelines, and occupational and previous medical history was taken through a standardized interview. Air-borne asbestos was measured according to NIOSH method 7400. The air-borne asbestos concentrations ranged from 0.2-1.3 f/cc for asbestos textile, from 0.7-1.0 f/cc for brake lining, and from 6.3-7.8 f/cc during asbestos removal at ship repairing worksite. Of the 139 workers 25 had abnormal chest radiographic findings, and 10 of them had findings compatible with pneumoconiosis. When work history and current asbestos measurements were accounted, 9 workers who had more than 10 years of asbestos exposure history showed chest radiographic findings of pneumoconiosis with Finally, 4 workers showed finding of pulmonary fibrosis and/or pleural thickening at HRCT, and 2 of them had restrictive lung function changes. The study results showed that, among 139 subjects, there were 4(3%) definite asbestosis cases confirmed with HRCT. The prevalence of probable asbestosis was 7% for 10-14 years of exposure, 13% for 15-19 years of exposure, and 23% for 20 or more years of exposure. The prevalence of compensable asbestosis with abnormal lung function was 4-6% for those with 15 or more years of exposure.

SCORM 기반의 XML 학습 컨텐츠 검색 시스템

최병욱,송미숙,조정원 한국컴퓨터교육학회 2003 컴퓨터교육학회 논문지 Vol.6 No.1

차세대 인터넷 표준 언어인 XML(eXtensible Markup Language)은 데이터(data)와 표현(presentation) 그리고 구조(Structure)가 구분되기 때문에 어느 환경에서나 재사용성이나 재구성이 용이한 장점을 보이고 있다. 본 논문에서는 XML 문서를 가상교육 시스템(Virtual Education System)의 멀티미디어 컨텐츠로 범위를 제한하여 사용자 위주의 효율적인 검색 시스템을 구현한다. 본 시스템에서는 가상교육 표준안으로 제안되고 있는 SCORM(Sharable Content Object Reference Model)에서 정치한 SCO(Sharable Content Object)단위의 메타데이터를 기반으로 컨텐츠를 설계하고 각 문서를 키워드, 엘리먼트, 애트리뷰트 단위로 색인한다. 또한 사용자 인터페이스에서 앨리먼트 검색화면을 구조적으로 구성해줌으로써 사용자가 DTD(Document Type Definition)fl 대한 사전지식 없이도 검색이 가능하며, XML-QL로 재구성된 XML 문서의 형태와 XSL(extensible markup language Stylesneet Language)을 이용한 HTML 형태의 두 가지 결과화면을 제시함으로써 사용자 선택의 폭을 넓혀준다. XML(eXtensible Markup Language), next generation internet standard language has the advantage of easy re-use and re-structure in other computing environment because it has the separate data, presentation and structure. In this paper, we implement the efficient retrieval system for the general user by limiting the XML documents on the multimedia learning contents for the virtual education system. The system design is based on SCO Metadata unit defined in SCORM as the proposed virtual education standard. Each XML documents has three indexes keyword, element and attribute. Also, it makes Possible to retrieve data without previous knowledge of the 078 by making the element retrieval screen structure for the user interface. And it gives the user various result screen formats such as XML and HTML by restructuring the retrieval result through XML-QL and XSL, respectively.

개에서 발생한 양파 섭취에 의한 하인즈 소체 용혈성 빈혈 증례

이미선,윤기영,서경원,최호정,정성목,송근호,조종기,박성준 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2012 動物醫科學硏究誌 Vol.19 No.1

A 10 month-old Yorkshire Terrier was referred to the Veterinary Medical Teaching Hospital of Chungnam National University with the history of lethargy, bile pigment in urine and anorexia. Blood smear showed Heinz body, polychromatocytosis, schistocytosis, anisocytosis, which were the results from the oxidative injury. Hematology demonstrated a moderate anemia(PCV 22.4%, reference rage 35-55%), which was regeneration based on the degree of RPI (4.03, reference rage > 1). Serum biochemistry demonstrated mild elevation in total bilrubin, and mild decrease in total protein and albumin concentration. A diagnosis of Heinz body hemolytic anemia secondary to onion ingestion was made and treated with fluid therapy, oxygen and antioxidant drugs. The dog recovered without any complication.

한국인 제2형 당뇨병 환자의 골격근에서 인슐린 신호전달체계의 결함

최준혁,이관우,김효정,이동훈,이종우,김정은,엄현채,김경미,최성이,정윤석,김현만 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 제2형 당뇨병에서 나타나는 인슐린 저항성은 간, 지방, 근육 같은 말초조직에서 인슐린의 작용이 떨어지는 것을 말한다. 제2형 당뇨병의 발생기전에 인슐린 저항성과 인슐린 분비능 저하가 같이 관여함은 잘 알려진 사실이다. 인슐린의 세포내에서의 저항성을 규명하기 위한 인슐린의 세포내 신호전달체계에 대한 연구가 활발히 진행되고 있으며 몇몇 연구에서 인슐린 저항성을 가진 골격근육에서 IRS와 관련된 PI3-kinase의 활성감소와 Akt kinase의 활성감소를 보고하고 있으나 아직까지 명확하게 그 기작이 설명되어지지 않고 있다. 본 연구에서는 정상성인, 제2형 당뇨병 환자를 대상으로 경구당부하검사 및 인슐린 클램프검사를 시행하고 인슐린 클램프 검사시 대상인의 근육을 채취하여 인슐린 신호전달 체계(IR-β, IRS, Akt(PKB, Rac) kinase, GSK-3)를 연구하였다. 방법: 연구대상자는 한국인으로서 경구당부하검사상 정상인 및 당뇨병 환자 각각 11명, 9명을 대상으로 하였으며, 정상인은 건강인으로 과거력상 당대사에 영향을 줄 질환이 없고, 현재 당대사에 영향을 줄 약물 복용 및 다른 소견이 없는 경구당부하검사상 정성 내당능을 보이는 대상자로 하였다. 당뇨병환자는 모두 제2형 당뇨병 환자로 이환기간이 만 5년 이내인 경우로 하고, 인슐린으로 치료하는 대상자는 제외하도록 하였다. 대상자의 연령, 체질량지수, 체지방량, 공복시 총콜레스테롤, 중성지방, 고밀도지단백 콜레스테롤 및 HbA1c, 인슐린, C-peptide를 측정하였고, "HOMA model"을 이용하여 베타세포의 기능와 인슐린저항성 정도를 평가하였다. 정상혈당클램프 검사(euhlycemic hyperinsulinemic clamp test)를 시행하고 인슐린 투입 전과 인슐린 투입 30분후, 두차례에 걸쳐 대퇴부 근육생검을 실시한후 western 법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 측정하였다. 결과: 정상인 11명과 당뇨병 환자 9명을 대상으로 하였으며 대상자의 평균 연령, 평균 체질량지수, 체지방량, 허리/엉덩이 둘레의 비(waist hip ratio; WHR)는 두 군간에 차이가 없었다. 평균 공복혈당은 정상군 98.0±0.3㎎/dL, 당뇨병군 208.1±16.5㎎/dL(p<0.05), HbA1c는 정상군 5.4±0.5%, 당뇨병군 9.2±0.6%(p<0.05)였다. "HOMA model"을 이용한 베타세포의 기능과 인슐린저항성은 정상군 56.4±8.5%, 1.4±0.2, 당뇨병군 72.2±52.3%(p<0.01), 10.2±6.3(p<0.01)였으며 정상혈당클램프 검사상 포도당 이용률은 정상군 8.2±0.6㎎/㎏/min, 당뇨병군 3.7±1.1㎎/㎏/min(p<0.01)로 정상군과 당뇨병군간에 유의한 차이를 나타내었다. Western blot법으로 IR-β, IRS, Akt kinase, GSK-3의 인산화량을 인슐린 투입전과 인슐린 투입 30분후 측정하였을 때 IR-β에서는 정상군이 103.9±2.3에서 241.3±18.6, 당뇨군이 108.9±2.2에서 198.7±6.3으로 증가하였다(p=NS). 이는 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 통계적인 차이가 없었다. IRS에서는 정상군이 111.6±7.3에서 295.6±17.2, 당뇨군이 114.5±6.1에서 222.0±23.2로 증가하였으며(p<0.05), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 24% 감소하였다. Akt kinase에서는 103.4±6.0에서 416.8±29.5로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 43% 감소하였다. GSK-3에서는 정상군이 107.7±6.7에서 595.7±28.1, 당뇨군이 104.3±4.8에서 443.3±12.9로 증가하였으며(p<0.01), 인슐린 투입후 당뇨병군이 정상군과 비교하여 인산화량의 증가정도가 약 25% 감소하였다. 결론: 제2형 당뇨병 환자에서 정상인과 비교하여 인슐린 자극후 IR-β는 인산화량의 증가정도가 큰 차이가 없었으나, IRS, Akt kinase, GSK-3에서는 인산화량의 증가 정도가 감소되는 것으로 보아 상위 인슐린 신호전단체계부터 결함이 있는 것으로 생각된다. Background: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-β), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes(n=9) and control subjects(n=11). Methods: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphroylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-β), Akt and GSK-3. Result: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA_1c in controls and diabetic patients were 98.0±0.3 and 208.1±16.5ng/dl, and 5.4±0.5 and 9.2±0.6%, and 1.4±0.2 in the control subjects, and 72.2±52.3%(p<0.01) and 10.2±6.3(p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp test were 8.2±0.6㎎/㎏/min and 3.7±1.1ng/㎏/min in the control subjects and in the diabetic patients, respectively(p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively(p<0.05). Conclusion: In Korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus (J Kor Soc Endocrinol 17:685∼697, 2002).

성장기 쥐에서 이소플라본 첨가수준이 골밀도 및 골함량에 미치는 영향

최미자,정윤정 啓明大學校 生活科學硏究所 2005 科學論集 Vol.31 No.-

The purpose of this study was to examine the effects of isoflavones supplementation on bone mineral density and bone mineral content in growing female Sprague-Dawley rats. Twenty-seven rats were divided into three groups casein diet, casein+1/2IF(1.7 mg isoflavones/g protein)diet, and casein+IF(3.4mg isoflavones/g protein) diet. All rats has been fed on experimental diet and deionized water ad libitum for 9 weeks. Bone mineral density(BMD) and bone mineral content(BMC) were measured using PIXImus(GE Lunar Co, Wisconsin, USA.) in spine and femur on 9 weeks after feeding. Diet did not affect weight gain and mean food intake. Food efficiency ratio was lower in casein +IF groups. The casein+IF and casein+1/2IF group had significantly higher spine and femur bone mineral density than the casein group. We found that bone mineral density effected by isoflavones supplementation has been resulted differently in accordance with the type of bone. Therefore, isoflavones supplementation may be beneficial on spine and femur BMD increasement in growing female rats.