Pivotal role of the RanBP9-cofilin pathway in Aβ-induced apoptosis and neurodegeneration

Woo, J A,Jung, A R,Lakshmana, M K,Bedrossian, A,Lim, Y,Bu, J H,Park, S A,Koo, E H,Mook-Jung, I,Kang, D E Macmillan Publishers Limited 2012 CELL DEATH AND DIFFERENTIATION Vol.19 No.9

Neurodegeneration associated with amyloid β (Aβ) peptide accumulation, synaptic loss, neuroinflammation, tauopathy, and memory impairments encompass the pathophysiological features of Alzheimer's disease (AD). We previously reported that the scaffolding protein RanBP9, which is overall increased in brains of AD patients, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of amyloid precursor protein (APP) and β1-integrin, respectively. Here, we show that RanBP9 protein levels are increased by fourfold in FAD mutant APP transgenic mice. Accordingly, RanBP9 transgenic mice demonstrate significantly increased synapse loss, neurodegeneration, gliosis, and spatial memory deficits. RanBP9 overexpression promotes apoptosis and potentiates Aβ-induced neurotoxicity independent of its capacity to promote Aβ generation. Conversely, RanBP9 reduction by siRNA or gene dosage mitigates Aβ-induced neurotoxicity. Importantly, RanBP9 activates/dephosphorylates cofilin, a key regulator of actin dynamics and mitochondria-mediated apoptosis, and siRNA knockdown of cofilin abolishes both Aβ and RanBP9-induced apoptosis. These findings implicate the RanBP9–cofilin pathway as critical therapeutic targets not only for stemming Aβ generation but also antagonizing Aβ-induced neurotoxicity.

청가시덩굴 추출물의 기능성 원료 표준화를 위한 지표성분 Resveratrol, trans-Scirpusin A의 분석법 개발 및 검증

권진관(Jin Gwan Kwon),정연우(Yeon Woo Jung),최윤혁(Yun-Hyeok Choi),이지은(Ji Eun Lee),정원식(Wonsik Jeong),이정아(Jung A Lee),최춘환(Chun Whan Choi),안은경(Eun-Kyung Ahn),최용문(Yongmun Choi),홍성수(Seong Su Hong) 한국식품영양과학회 2022 한국식품영양과학회지 Vol.51 No.11

본 연구는 HPLC를 이용하여 청가시덩굴 추출물을 개별인정형 건강기능식품의 기능성 원료로 개발하기 위한 원료 표준화의 일환으로, 청가시덩굴 추출물의 지표성분을 resveratrol과 trans-scirpusin A로 설정하고 이에 대한 HPLC 분석법을 확립하여 유효성의 검증을 실시하였다. 분석법 유효성 검증은 특이성, 직선성, 정확도, 정밀도, 검출한계 및 정량한계 등을 통해 분석법의 신뢰성을 검증하였으며, 그 결과 표준용액과 청가시덩굴 추출물 간의 HPLC 크로마토그램 및 UV spectrum의 일치 여부 등의 비교를 통해 다른 물질과 간섭 없이 피크가 분리된 것으로 특이성을 확인하였다. 또한 표준용액 검량선의 상관계수(R²)는 0.9999로 매우 우수한 직선성으로 관찰되어 분석에 적합한 것으로 확인되었으며, 검량선의 기울기 및 표준편차를 이용한 검출한계는 resveratrol이 0.98 μg/mL, trans-scirpusin A는 0.49 μg/mL였고 정량한계는 resveratrol이 2.98 μg/mL, trans-scirpusin A는 1.48 μg/mL로 각각 확인되었다. 청가시덩굴 추출물에 표준물질을 3개 농도 첨가하고 분석한 회수율은 resveratrol이 98.77~99.24%, trans-scirpusin A는 98.45~99.45%로 나타나 정확성이 있는 것을 확인할 수 있었다. 청가시덩굴 추출물의 조제 농도 2.2, 4.4 및 6.6 mg/mL에서 반복성은 resveratrol이 0.99~1.22%, trans-scirpusin A는 1.12~1.32%를, 실험실 내 정밀성에서는 일내 정밀성은 resveratrol이 0.67~0.87%, trans-scirpusin A는 1.18~1.33%로 나타났고 일간 정밀성은 resveratrol이 0.93~1.22%, trans-scirpusin A는 1.33~2.27%로 확인되어 본 분석법은 정밀성이 있음을 확인할 수 있었다. 이상의 분석결과를 통해 확립된 청가시덩굴 추출물의 지표성분인 resveratrol과 trans-scirpusin A의 HPLC 분석법은 적합한 시험법으로 검증되었으며, 본 시험법은 향후 청가시덩굴 추출물의 건강기능식품 기능성 원료 개발과 표준화를 위한 기초자료로 활용될 것으로 사료된다. This study was undertaken to establish an analytical method using high-performance liquid chromatography (HPLC). HPLC for the standard determination of resveratrol and trans-scirpusin A as functional ingredients in Smilax sieboldii extract. We evaluated the specificity, linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) of various analytical methods for detecting resveratrol and trans-scirpusin A using HPLC. The specificity was confirmed by the chromatogram obtained using the HPLC analytical method. Also, the results of UV and the coefficient of correlation (R²) obtained was 0.999, which confirmed that this was a suitable analysis with high linearity. The LOD was 0.98, 0.49 μg/mL, and LOQ was 2.98, 1.48 μg/mL, which was confirmed as a suitable limit level for the analysis of resveratrol and trans-scirpusin A content in the S. sieboldii extract. The recovery of resveratrol and trans-scirpusin A content was determined to be 98.77±0.73∼99.24±1.47% and 98.45±1.18∼99.45±1.66%, respectively, indicating high accuracy. The intra-day repeatability and the intra-laboratory precision of the daily repetition were confirmed to be 0.67∼0.87%, 1.18∼1.33% and 0.93∼1.22%, 1.33∼2.27%, respectively, for trans-scirpusin A, for the relative standard deviation. These results indicate that the reported HPLC method is simple, reliable, and reproducible for the detection of resveratrol and trans-scirpusin A in S. sieboldii extract.

한국인에서 혈소판 당단백 Ⅱb/Ⅲa 유전자 다형성과 관동맥 성형술 후 재 협착과의 관계

이민수,이정우,김보영,임대승,강정아,김정희,김윤철,성보영,최성준,성인환,전은석 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.2

Platelet aggregation is the final pathway of acute coronary syndrome such as acute myocardial infarction and unstable angina. Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and yon Willebrand factor and it plays an important role in platelet aggregation and in the pathogenesis of acute coronary syndrome. It is known that polymorphism of the gene that encoding platelet glycoprotein IIb/IIIa(PI^A1/A2) is strongly related to acute coronary syndrome in Caucasian, but not in Koreans. We investigated relationship between platelet glycoprotein llb/Illa gene polymorphism and restenosis of coronary artery after angioplasty in Koreans. Total 371 patients(M=251. F=120) were enrolled. Angioplasty group comprised 143 patients who underwent coronary angioplasty, and in the angioplasty group, restenosis group comprised with the 65 patients who had restenotic lesion over 50% of luminal diameter in follow-up coronary angiography. Normal group comprised 153 patients who had no significant angiographic lesion and variant angina group comprised 75 patients who were positive in ergonovine test. Genomic DNA was extracted from peripheral arterial blood. To determine the frequency of P1^A1/A2 genotype, polymerase chain reaction(PCR) was done and the product was restricted with Mspl. 3%. agarrose gel electrophoresis showed restriction fragment length polymorphism. Clinical profile and risk factor were also reviewed. Among all 371 patients of study group, genotype of only one patients in restenosis group if is proven to be PI^A1/A2 heterozygote. All patients of normal study group, no restenosis group, and the other patients in restenosis group have an PI^A1 homozygote genotype. In our study, platelet glycoprotein IIb/Illa polymorphism has no relationship with restenosis of the coronary artery after angioplasty in Koreans. But the genotypic frequency of platelet glycoprotein IIb/IIIa gene polymorphism in Koreans is concordant with that of previous studies.

Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway

Roh, Seung-Eon,Woo, Jung A.,Lakshmana, Madepalli K.,Uhlar, Courtney,Ankala, Vinishaa,Boggess, Taylor,Liu, Tian,Hong, Yun-Hwa,Mook-Jung, Inhee,Kim, Sang Jeong,Kang, David E. The Federation of American Societies for Experimen 2013 The FASEB Journal Vol.27 No.12

<P>Mitochondrial dysfunction and synaptic damage are important features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and tau. We reported previously that the scaffolding protein RanBP9, which is overall increased in brains of patients with AD and in mutant APP transgenic mice, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of APP and β1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration <I>in vitro</I> and <I>in vivo</I> and mediates Aβ-induced neurotoxicity. Here we show in primary hippocampal neurons that RanBP9 potentiates Aβ-induced reactive oxygen species (ROS) overproduction, apoptosis, and calcium deregulation. Analyses of calcium-handling measures demonstrate that RanBP9 selectively delays the clearance of cytosolic Ca<SUP>2+</SUP> mediated by the mitochondrial calcium uniporter through a process involving the translocation of cofilin into mitochondria and oxidative mechanisms. Further, RanBP9 retards the anterograde axonal transport of mitochondria in primary neurons and decreases synaptic mitochondrial activity in brain. These data indicate that RanBP9, cofilin, and Aβ mimic and potentiate each other to produce mitochondrial dysfunction, ROS overproduction, and calcium deregulation, which leads to neurodegenerative changes reminiscent of those seen in AD.—Roh. S.-E., Woo, J. A., Lakshmana, M. K., Uhlar, C., Ankala, V., Boggess, T., Liu, T., Hong, Y.-H., Mook-Jung, I., Kim, S. J., Kang, D. E. Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway.</P>

기상장 수치모의를 이용한 김해지역 대기질 예측

이화운,정우식,임헌호,이강열,노순아 부산대학교 환경문제연구소 2003 環境硏究報 Vol.21 No.-

For the purpose of prediction air quality in Kimhae area, ISC3 and UAM were used. As the study area is located in a coastal area, the atmospheric flow is strong1y affected by the sea breeze. The air quality model results show that the dirunal variation pattern of pollutants is consistent with observed spatial and temporal features, as a whole.

인간의 공감 측정에 대한 기술 및 활용방안

진정아(Jung-A Jin),김선우(Sun-Woo Kim),최연성(Yeon-Sung Choi) 한국정보전자통신기술학회 2016 한국정보전자통신기술학회논문지 Vol.9 No.1

다른 사람이 차 문에 손가락을 찧는 것을 보면 마치 내게 일어난 일처럼 움찔하지 않는가? 소설을 읽고 감정을 느끼는 것은 왜일까? 이는 공감하기 때문이다. 공감이란 “다른 사람이 느끼는 감정을 목격하거나 기대하는 순간에 정서적으로 반응하는 것”이다. 즉, 공감은 함께 느끼는 것이다. 본 논문에서는 이러한 공감을 측정하는 방법에 대해서 기술하고자 한다. 사람의 감정을 측정하는 것은 쉽지가 않다. 사람들이 소통하는 방식이 다양하기 때문이다. 사람마다 공감을 표현하는 것과 느끼는 감정이 다 다르기 때문에 다양한 방법의 데이터 분석이 필요하다. 이를 위해 본 논문에서는 짧은 단위(1초 단위: 응, 좋아, 아하 등)의 음성과 Head Nodding을 이용한 새로운 공감 측정방법을 제안하려고 한다. When another person is injured finger in the car door do you know that feeling? Do you feel the emotion reading a novel? How do you feel the emotion of other person? This is due to empathy. Empathy is feel emotion or react emotionally of other person. Empathy is feel together. In this paper, we are going to describe how to measure these empathy. Before you begin, it is not easy to measure human empathy. The reason is that humans have communications system is diverse. Because it is different feel and be expressed sympathy for each person, is required various data analysis. In this paper, we proposed a new method to utilize Head Nodding and a short speech units (1sec : A-ha, Yes, Good etc.).

Correction: Electrochemical and electrocatalytic reaction characteristics of boron-incorporated graphene <i>via</i> a simple spin-on dopant process

Jang, A.-Rang,Lee, Young-Woo,Lee, Sang-Seok,Hong, John,Beak, Seong-Ho,Pak, Sangyeon,Lee, Juwon,Shin, Hyeon Suk,Ahn, Docheon,Hong, Woong-Ki,Cha, SeungNam,Sohn, Jung Inn,Park, Il-Kyu The Royal Society of Chemistry 2018 Journal of Materials Chemistry A Vol.6 No.17

<P>Correction for ‘Electrochemical and electrocatalytic reaction characteristics of boron-incorporated graphene <I>via</I> a simple spin-on dopant process’ by A-Rang Jang <I>et al.</I>, <I>J. Mater. Chem. A</I>, 2018, DOI: 10.1039/c7ta09517a.</P>

<i>Scutellaria baicalensis</i> Extracts and Flavonoids Protect Rat L6 Cells from Antimycin A-Induced Mitochondrial Dysfunction

Im, A-Rang,Kim, Young-Hwa,Uddin, Md. Romij,Lee, Hye Won,Chae, Seong Wook,Kim, Yun Hee,Jung, Woo Suk,Kang, Bong Ju,Mun, Chun Sun,Lee, Mi-Young Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P>Antimycin A (AMA) damages mitochondria by inhibiting mitochondrial electron transport and can produce reactive oxygen species (ROS). ROS formation, aging, and reduction of mitochondrial biogenesis contribute to mitochondrial dysfunction. The present study sought to investigate extracts of <I>Scutellaria baicalensis</I> and its flavonoids (baicalin, baicalein, and wogonin), whether they could protect mitochondria against oxidative damage. The viability of L6 cells treated with AMA increased in the presence of flavonoids and extracts of <I>S. baicalensis</I>. ATP production decreased in the AMA treated group, but increased by 50% in cells treated with flavonoids (except wogonin) and extracts of <I>S. baicalensis</I> compared to AMA-treated group. AMA treatment caused a significant reduction (depolarized) in mitochondrial membrane potential (MMP), whereas flavonoid treatment induced a significant increase in MMP. Mitochondrial superoxide levels increased in AMA treated cells, whereas its levels decreased when cells were treated with flavonoids or extracts of <I>S. baicalensis</I>. L6 cells treated with flavonoids and extracts of <I>S. baicalensis</I> increased their levels of protein expression compared with AMA-treated cells, especially water extracts performed the highest levels of protein expression. These results suggest that the <I>S. baicalensis</I> extracts and flavonoids protect against AMA-induced mitochondrial dysfunction by increasing ATP production, upregulating MMP, and enhancing mitochondrial function.</P>

Suppressive Effect of Fermented Angelica tenuissima Root Extract against Photoaging: Possible Involvement of Hemeoxygenase-1

( Yun-a Park ),( Sung Ryul Lee ),( Jin Woo Lee ),( Hyun Jung Koo ),( Seon-a Jang ),( Seung-won Yun ),( Hyun Ju Kim ),( Jeong Suk Woo ),( Myung Rye Park ),( Se Chan Kang ),( Youn Kyu Kim ),( Eun-hwa So 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.8

Angelica tenuissima root has historically been used as a traditional medicine in Korea. Previous studies have identified the anti-melanogenic effects of the extract of A. tenuissima root fermented by Aspergillus oryzae (FAT). This study investigated the protective effects of FAT against ultraviolet light B exposure (UVB; 30 mJ/㎠) in HaCaT (human keratinocyte) or Hs68 (human foreskin fibroblast) skin cells. FAT treatment was able to stimulate wound healing rate at the basal condition. FAT also favored the maintenance and/or improvement of extracellular matrix impairment caused by UVB irradiation through: 1) upregulation of procollagen Type-1 synthesis and secretion; 2) suppression of MMP-1 and elastase expression. FAT was able to play a role in the attenuation of inflammatory responses caused by UVB irradiation via upregulation of photo-protective hemeoxygease-1 and suppression of proinflammatory cyclooxygenase-2 expression. After further verification of the anti-photoaging potential of FAT, it could be utilized as an effective ingredient in anti-aging and anti-wrinkle cosmetics.

철섬아연광의 증류법에 의한 아연화제조

김정국,우종안 대한금속재료학회(대한금속학회) 1968 대한금속·재료학회지 Vol.6 No.1

This report describes a technical feasibility study of employing the distillation process on producing zinc white from marmatite. The marmatite concentrate was roasted in a 500 gram rotary roaster in order to produce calcine. Distillation tests were made batchwise in a 300 gram Globar furnace at different temperatures ranged 900 to 1200℃, using anthracite as reductant and lime stone as flux. The anthracite and lime stone used in these tests were assayed 57.8% of fixed carbon and 50% of calcium oxide, respectively. Zinc vapor produced in the furnace was immediately oxidized at the vapor outlet, and zinc white fume was simultaneously sent to the bag collector pneumatically. Above results of the tests indicated that (1) anthracite, as reducing agent, can be substituted for coke; d(2) the optimum charge ratio of calcine: anthracite: lime stone was 10:9:1; (3) distillation time was reduced gradually with increasing temperature; and (4) at 1,200℃, commercial grade zinc white was produced with more than 95% recovery for an hour operation.