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Effect of the cellular cholesterol on the expression of human ACAT1 56-kD isoform

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Effect of the cellular cholesterol on the expression of huma...

中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Dong-Qing Guo Guang-Jing Hu Jia-Jia Xu Xiao-Nan Zhao Jia Chen Ming Zhu Lei Qian catherine C.Y.Chang Bao-Liang Song Ta-Yuan Chang Ying Xiong Bo-Liang Li State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Department of Biochemistry Dartmouth Medical School Hanover NH 03756 USA

Acyl-coenzyme A:cholesterol acyltransferase(ACAT) catalyzes the formation of cholesteryl ester from cholesterol and longchain fatty acyl-coenzyme A, and is a key enzyme in the cellular cholesterol metabolism. So far, two human ACAT1 isoforms(50- and 56-kD) have been identified. We have previously reported that the expression of 50-kD isoform and chromosome 1-derived ACAT1 mRNA can be up-regulated by the inflammatory factor interferon-γ(IFN-γ) or tumor necrosis factor-α(TNF-α) specifically in human monocytic cells. Recently, it has been uncovered that human ACAT1 56-kD isoform is translated from a multi-chimeric mRNA by a novel exo-endo trans-splicing between an asAmp transcript and the ACAT1 4.3-kb chimeric mRNA with an optional long 5’-UTR, which contains chromosome 7-derived lncRNA ACAT1C7 sequence to decay its linked ACAT1 mRNA. Based on those progresses, this work focuses on the effect of the cellular cholesterol on the expression of human ACAT1 56-kD isoform. First of all, it is interestingly observed that human ACAT1 56-kD isoform is induced in monocytic cell line THP-1 by the treatment of IFN-γ plus ATRA or TNF-α together with the high dose of the oxidized low-density lipoprotein(oxLDL), which leads to the high-level cholesterol in cells. Next, when the high dose of mevalonate is used to boost cellular cholesterol level, human ACAT1 56-kD isoform is also increased in different non-monocytic cell lines. Besides, we have transfected cells with plasmid pVk-ACAT1-C7, which can highly express chromosome 7-derived lncRNA ACAT1C7, and then observed that human ACAT1 56-kD isoform is evidently increased. Furthermore, by using actinomycin D to inhibit the mRNA transcription, the RT-qPCR results indicate that the high-level cellular cholesterol can promote the decay of chromosome 1-derived ACAT1 mRNA transcribed by polymerase II. Accordingly, we speculate that the high-level cellular cholesterol may promote the polymerase IⅡtranscription of chromosome 7-derived lncRNA A

关键词： Human ACAT1 56-kD isoform Cellular cholesterol mRNA decay Trans-splicing lncRNA ACAT1C7

Impact of human ACAT1 on the dynamic free cholesterol in plasma membrane of neural cell line SK-N-SH

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Impact of human ACAT1 on the dynamic free cholesterol in pla...

脂质组学与脂蛋白的新功能——第十二届全国脂质与脂蛋白学术会议

作者： Ming Zhu Xiao-Nan Zhao Jia Chen Jia-Jia Xu Guang-Jing Hu Dong-Qing Guo Qin Li Xiao-Wei Zhang catherine C.Y.Chang Bao-Liang Song Ta-Yuan Chang Ying Xiong Bo-Liang Li State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of Sciences Department of Biochemistry Dartmouth Medical School

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Impact of human ACAT1 on the dynamic free cholesterol in plasma membrane of neural cell line SK-N-SH

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Impact of human ACAT1 on the dynamic free cholesterol in pla...

中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Ming Zhu Xiao-Nan Zhao Jia Chen Jia-Jia Xu Guang-Jing Hu Dong-Qing Guo Qin Li Xiao-Wei Zhang catherine C.Y.Chang Bao-Liang Song Ta-Yuan Chang Ying Xiong Bo-Liang Li State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Department of Biochemistry Dartmouth Medical School Hanover NH 03756 USA

Acyl-CoA:cholesterol acyltransferase(ACAT) is an intracellular exclusive enzyme which utilizes long-chain fatty acyl-CoA and free cholesterol as substrates to form cholesteryl esters. It is a key enzyme involved in maintaining cellular cholesterol homeostasis, and plays important roles in some serious human diseases including atherosclerosis, Alzheimer’s disease(AD) as well as cancer. In mammals, two ACAT genes encoding ACAT1 and ACAT2 have been identified. In this work, we report the impact of human ACAT1 on the dynamic free cholesterol in plasma membrane(PM-FC) of neural cell line SK-N-SH. First, the Filipin staining and PM-FC determining assays indicate that the increase of the PM-FC content of neural cell line SK-N-SH is in dose and time dependent manners by the ACAT1 inhibition, while the western blot analyses display that the α-processing of amyloid precursor protein(APP) mainly on the plasma membrane can be inversely decreased. More importantly, we have observed that the decreased α-processing of APP by the ACAT1 inhibition can be conversely enhanced when depleting the increased PM-FC directly by methyl-β-cyclodextrin, meaning that the ACAT1 inhibition can impact the dynamic PM-FC which leads to the change of APP α-processing on the plasma membrane of neural cell line SK-NSH. Then, under the different levels of cellular cholesterols by inhibiting the absorption, efflux, synthesis of cholesterolsand/or increasing cholesterols by adding LDL or mevalonate in culture media, the results show that the ACAT1 inhibition can evidently impact the dynamic PM-FC. Finally, further evidences confirm that the α-processing of APP affected by the dynamic PM-FC through the ACAT1 activity change can be mimicked by the RNAi knockdown and overexpression of ACAT1 in neural cell line SK-N-SH. These data suggest that ACAT1 impacting the dynamic PM-FC may play important role in neural cells.

关键词： ACAT1 Dynamic free cholesterol Plasma membrane Alpha-processing of APP Neural cell line

在实验的涡轮机中:泰特现代美术馆与集体行为的新依据

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艺术博物馆 2021年第6期 14-29,2,1,188-189页

作者：卡特琳娜·贝尔纳尔高振华(译) 巴黎狄德罗大学《艺术博物馆》杂志

艺术实验以及用以定义它的概念,自前卫时代以来已经经历了大幅度变化,但实验仍然部分得到批评界的支持。本文聚焦近期在装置和行为艺术领域的实验,以及这些作品可以如何围绕美学实验通过其与我们当代感觉中枢复杂且往往带有冲突的关系... 详细信息

艺术实验以及用以定义它的概念,自前卫时代以来已经经历了大幅度变化,但实验仍然部分得到批评界的支持。本文聚焦近期在装置和行为艺术领域的实验,以及这些作品可以如何围绕美学实验通过其与我们当代感觉中枢复杂且往往带有冲突的关系提供的批判杠杆为我们带来启发。我们依托于泰特现代美术馆为联合利华系列(2000—2012)委托创作的某些最杰出的装置和行为的案例,试图理解伟大的前卫所想象的实验的批判性如何被在景观体制内工作的艺术家扭曲和重新发明,同时又忠实于实验的敏锐精神。我们的首要意图是返回德比的约瑟夫·赖特的伟大油画《关于空气泵中的鸟的实验》(1768)等作品所体现的科学与艺术实验的语义配对,从而探索实验的实证主义遗产。我们将类似朵丽丝·萨尔赛多的《示播列》(2008)和蒂诺·塞加尔的《这些联系》(2012)的作品置入漫长的历史和批判视野,试图突出实验的一个仍旧相对探索不足的侧面:在其与批判知识关系中的有形性和感觉的侧面。我们让实验依赖于感觉和思考或经验和概念之间的微妙的张力,以试图展示当代实验如何重新发明了这样的张力。联合利华系列的作品被放在了博物馆机器及其吸引经济的中心位置,突出了通常将感觉束缚在一个复杂批判立场的感觉经济。这些作品与文化产业强加的感觉体制合作又与之对立,形成复杂的经验寓意,参观者在这些寓意中的体验迈向了差别化的处世模式。我们主张,尤其是其集体逻辑在私与公、感觉和团体文化的连接点上让我们捕捉我们当前的视觉性和体验的体制。

关键词：实验艺术当代艺术装置艺术行为艺术泰特现代美术馆联合利华系列朵丽丝·萨尔赛多塞加尔·蒂诺

Semireplication-competent vesicular stomatitis virus as a novel platform for oncolytic virotherapy

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世界最新医学信息文摘 2015年第5期 245-245页

作者： Alexander Muik catherine Dold Yvonne Gei Andreas Volk Marina Werbizki Ursula Dietrich Dorothee von Laer

Among oncolytic viruses, the vesicular stomatitis virus(VSV) is especially potent and a highly promising agent for the treatment of cancer. But, even though effective against multiple tumor entities in preclinical animal models, replicationcompetent VSV exhibits inherent neurovirulence, which has so far hindered clinical development. To overcome this limitation,replication-defective VSV vectors for cancer gene therapy have been tested and proven to be safe. However, gene delivery was inefficient and only minor antitumor efficacy was observed. Here, we present semireplicationcompetent vector systems for VSV(sr VSV), composed of two trans-complementing, propagation-deficient VSV vectors. The de novo generated deletion mutants of the two VSV polymerase proteins P(phosphoprotein) and L(large catalytic subunit), VSVΔP and VSVΔL respectively, were used mutually or in combination with VSVΔG vectors. These sr VSV systems copropagated in vitro and in vivo without recombinatory reversion to replication-competent virus. The sr VSV systems were highly lytic for human glioblastoma cell lines,spheroids, and subcutaneous xenografts. Especially the combination of VSVΔG/VSVΔL vectors was as potent as wild-type VSV(VSV-WT) in vitro and induced long-term tumor regression in vivo without any associated adverse effects. In contrast, 90% of VSV-WT-treated animals succumbed to neurological disease shortly after tumor clearance. Most importantly, even when injected into the brain, VSVΔG/VSVΔL did not show any neurotoxicity. In conclusion, sr VSVis a promising platform for virotherapeutic approaches and also for VSV-based vector vaccines, combining improved safety with an increased coding capacity for therapeutic transgenes, potentially allowing for multipronged approaches.

关键词： Vesicular stomatitis virus Oncolytic virus Virotherapy Malignant glioma

Late ischemic stroke and brachiocephalic thrombus in a 65-year-old patient six months after COVID-19 infection:A case report

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World Journal of Hematology 2022年第2期9卷 13-19页

作者： Kristen Jane Kilby catherine Anderson-Quiñones Keith Richard Pierce Kirollos Gabrah Ankur Seth Allison Brunson Department of Pharmacy Baptist Memorial Hospital-MemphisMemphisTN 38120United States College of Medicine University of Tennessee Health Science CenterMemphisTN 38163United States College of Osteopathic Medicine New York Institute of TechnologyJonesboroAR 72401United States

BACKGROUND Although it is well established that coronavirus disease 2019(COVID-19)is associated with inflammation and a prothrombotic state leading to stroke and venous thromboembolism(VTE),the nuances of this association are yet to be uncovered[1].Many studies link elevations in inflammatory markers to cases of *** reports of thromboembolism associated with COVID-19 occur in the venous circulation during or just after the initial hospitalization due to COVID-19[2].It is unclear how long the hypercoagulable effect of COVID-19 *** SUMMARY We present a unique case of a 65-year-old-female who presented to her primary care doctor with a sore throat,cough,fatigue,congestion,diarrhea,headache,and *** tested positive for severe acute respiratory syndrome coronavirus 2 and received a bamlanivimab infusion 9 days *** recovering from the acute illness,she received the Pfizer-BioNTech COVID-19 *** later,she presented to the Emergency Department(ED)complaining of right sided shoulder pain and motor weakness in her left hand while trying to type on a *** presentation to the ED,her calculated Padua prediction score for risk of VTE was two and inflammatory markers were not *** was found to have a brachiocephalic artery occlusion as well as an ischemic stroke which was treated with *** This case suggests hypercoagulability due to COVID-19 may extend further than current literature suggests,to at least six months.

关键词： COVID-19 Stroke SARS-CoV-2 Thrombus Vaccine Case report

*** in a mouse model for Zellweger spectrum disorder

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Annals of Eye Science 2018年第1期 418-418页

作者： catherine Argyriou Anna Polosa Bruno Cecyre Erminia Di Pietro Monica Hsieh Jean-Francois Bouchard Pierre Lachapelle Nancy Braverman Human Genetics McGill UniversityMontrealQCCanada Ophthalomology McGill UniversityMontrealQCCanada Optometry University of MontrealMontrealQCCanada

Background:Zellweger spectrum disorder(ZSD)is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome *** leading to blindness is one of the major untreatable handicaps faced by patients with ZSD but is not well characterized,and the requirement for peroxisomes in retinal health is *** address this and to inform future therapeutic studies,we examined the progression of retinopathy in our murine model for the common PEX1-G843D ***:Retinal electrophysiology(ffERG)and histology were performed in a cohort of Pex1-G844D(equivalent to human G843D)mice from 2 to 32 *** acuity was assessed using *** levels of PEX1-G843D protein,its binding partner Pex6,and its putative ligand Pex5(the peroxisome enzyme receptor)in the retina were determined by *** biochemical metabolites in the whole eye and retina were measured using LC/*** immunohistochemistry was used to visualize various cell ***:Cone ffERG response in the mutants remained residual(5%that of control)regardless of *** rod-mediated responses(50-70%of control)was reached at 4-6 wks,and then progressively decreased with age.B-waves were affected more severely than a-waves,while high frequency ERG components(oscillatory potentials)are better preserved than low frequency components(a-and b-waves).Visual evoked potential was diminished at 32 *** of visual acuity using optokinetics showed low visual reflexes by 11-13 weeks of *** found normal amounts of Pex1-G844D,Pex6,and Pex5 protein in retina,suggesting that the mutated protein is not *** of peroxisome metabolites showed elevated very long chain fatty acids(VLCFA)and decreased plasmalogens in the whole eye,indicative of peroxisome *** the retina,VLCFAs were not elevated,and only C22:6(docosahexaenoic acid)was decreased of the plasmalogens *** were

关键词： Zellweger spectrum disorder(ZSD) peroxisome disorder PEX1

A solution scan of societal options to reduce transmission and spread of respiratory viruses:SARS-CoV-2 as a case study

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Journal of Biosafety and Biosecurity 2021年第2期3卷 84-90页

作者： William J.Sutherland Nigel G.Taylor David C.Aldridge Philip Martin catherine Rhodes Gorm Shackelford Simon Beard Haydn Belfield Andrew J.Bladon Cameron Brick Alec P.Christie Andrew P.Dobson Harriet Downey Amelia S.C.Hood Fangyuan Hua Alice C.Hughes Rebecca M.Jarvis Douglas MacFarlane William H.Morgan Anne-ChristineMupepele Stefan J.Marciniak Cassidy Nelson SeánÓhÉigeartaigh Clarissa Rios Rojas Katherine A.Sainsbury Rebecca K.Smith Lalitha S.Sundaram Ann Thornton John Watkins Thomas B.White Kate Willott Silviu O.Petrovan BioRISC(Biosecurity Research Initiative at St Catharine’s) St Catharine’s CollegeCambridge CB21RLUK Department of Zoology University of CambridgeThe David Attenborough BuildingPembroke StreetCambridge CB23QZUK Tour du Valat Research Institute for the Conservation of Mediterranean Wetlands13200 ArlesFrance Centre for the Study of Existential Risk University of CambridgeCB21SBUK Department of Social Psychology University of AmsterdamNieuwe Achtergracht 129 B1018 WT AmsterdamNetherlands Department of Ecology and Evolutionary Biology 117 Eno HallPrinceton UniversityNJ 08544USA Institute of Ecology College of Urban and Environmental SciencesPeking UniversityBeijing 100871PR China Centre for Integrative Conservation Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesXishuangbannaYunnan 666303PR China Te Kura Putaiao-School of Science Auckland University of TechnologyAucklandNew Zealand School of Psychological Sciences University of Western AustraliaPerth35 Stirling HwyCrawley WA 6009Australia Nature Conservation and Landscape Ecology Biometry and Environmental System AnalysisUniversity of FreiburgGermany Cambridge Institute for Medical Research University of CambridgeCambridge Biomedical CampusThe Keith Peters BuildingHills RoadCambridge CB20XYUK Future of Humanity Institute University of OxfordOxford OX11PTUK Faculty of Kinesiology Sportand RecreationUniversity of Alberta2-130V Van Vliet 21 Complex(University Hall)EdmontonAlberta T6G 2H9Canada Division of Population Medicine School of MedicineCardiff UniversityCardiff CF144YSUK

Societal biosecurity–measures built into everyday society to minimize risks from pests and diseases–is an important aspect of managing epidemics and *** aimed to identify societal options for reducing the transmission and spread of respiratory *** used SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)as a case study to meet the immediate need to manage the COVID-19 pandemic and eventually transition to more normal societal conditions,and to catalog options for managing similar pandemics in the *** used a‘solution scanning’*** read the literature;consulted psychology,public health,medical,and solution scanning experts;crowd-sourced options using social media;and collated comments on a ***,we present a list of 519 possible measures to reduce SARS-CoV-2 transmission and *** provide a long list of options for policymakers and businesses to consider when designing biosecurity plans to combat SARS-CoV-2 and similar pathogens in the *** also developed an online application to help with this *** encourage testing of actions,documentation of outcomes,revisions to the current list,and the addition of further options.

关键词： Biosecurity Coronavirus COVID-19 Disease control New normal Public health

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东南亚孔子学院联席会议在京召开

孔子学院（中法文对照版） 2023年第5期 79-79页

作者：无白洁(翻译) 中国国际中文教育基金会不详

北京时间2023年7月20日上午,以“协同创新行稳致远”为主题的东南亚孔子学院联席会议在北京国际会议中心顺利召开,来自东南亚10个国家的孔子学院(课堂)及中外方合作院校代表近300人参会。中国国际中文教育基金会理事长杨卫为新建孔子学... 详细信息

北京时间2023年7月20日上午,以“协同创新行稳致远”为主题的东南亚孔子学院联席会议在北京国际会议中心顺利召开,来自东南亚10个国家的孔子学院(课堂)及中外方合作院校代表近300人参会。中国国际中文教育基金会理事长杨卫为新建孔子学院授牌。

关键词：教育基金会孔子学院协同创新联席会议东南亚北京国际会议中心