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.

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

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.

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.

청소년의 인터넷 게임중독의 극복에 있어 자기통제 및 부모통제의 조절적 역할

정형식,최수아,장미라 朝鮮大學校 經營經濟硏究所 2006 經營經濟硏究 = Management and economics research Vol.29 No.1

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

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.