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clusterin mRNA expression in apoptotic and activated rat thymocytes

Cell Research 2003年第1期13卷 49-58页

作者： JUNG-HYUNPARK,JEE-SUNPARK,SUNG-KYUJU,KWAN-BOKLEE,KWAN-HEEYOU,MYUNG-HEEKANG,Yoo-KYOUNGPARK,SHIN-YOUNGNA Experimental Department Department Department Department Department Department Institute Immunology Branch National Cancer Institute NIH Bethesda MD 20892 USA of Biology College of Natural Science Chungnam National University 220 Gung-dong Yuseong-gu Daejeon 305-764 Korea of Biology College of Natural Science Chungnam National University 220 Gung-dong Yuseong-gu Daejeon 305-764 Korea of Biology College of Natural Science Chungnam National University 220 Gung-dong Yuseong-gu Daejeon 305-764 Korea of Biology College of Natural Science Chungnam National University 220 Gung-dong Yuseong-gu Daejeon 305-764 Korea of Food and Nutrition Hannam University Daejeon 306-791 Korea of Food and Nutrition Hannam University Daejeon 306-791 Korea for Virology and Immunobiology University of Wuerzburg Versbacher Str. 7 97078 Wuerzburg Germany

clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exact biological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavily disputed, since data supporting both views have been reported in several independent studies. To clarify this issue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the present study, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis in thymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and after induction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering of apoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptotic processes. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expression was restricted to freshly isolated thymocytes. This

关键词： clusterin sgp-2 thymocytes apoptosis mRNA isoforms.

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clusterin in Alzheimer's disease: a player in the biological behavior of amyloid-beta

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Neuroscience Bulletin 2014年第1期30卷 162-168页

作者： Xiang Li Yifei Ma Xu Wei Yanpeng Li Huijuan Wu Jianhua Zhuang Zhongxin Zhao Department of Neurology Changzheng Hospital Second Military Medical University

Alzheimer＇s disease （AD） remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta （Aβ） peptides in the brain. The chaperone protein clusterin has, since its first discovery at the end of the 20^th century, been labeled as a cytoprotector. However, epigenetic studies showing that clusterin is associated with the severity and risk of AD, especially in the hippocampus, triggered studies to clarify its role in the pathogenesis of AD. It is true that clusterin can inhibit the aggregation of Aβ and therefore prevent further formation of senile plaques in the AD brain, yet it induces the formation of soluble forms of Aβ which are toxic to neurons. Another problematic finding is that clusterin is involved in a pathway through which Aβ has neurodegenerative effects intracellularly. Although the role of clusterin in the pathogenesis of AD is still not clear, this review specifically discusses the interactions between clusterin and Aβ, to open up the possibility of a potential therapeutic approach for treating AD.

关键词： clusterin Alzheimer's disease amyloid-beta peptides cytotoxicity cytoprotection

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clusterin: a multifaceted protein in the brain

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Neural Regeneration Research 2021年第7期16卷 1438-1439页

作者： Hee-Jung Moon Sarah K.Herring Liqin Zhao Department of Pharmacology and Toxicology School of PharmacyUniversity of KansasLawrenceKSUSA Neuroscience Graduate Program University of KansasLawrenceKSUSA Current address:Citoxlab A Charles River Company StilwellKSUSA

Late-onset Alzheimer 's disease(LOAD), the most common cause of dementia, currently affects 5.6 million Americans ages 65 and *** is a neurodegenerative disorder characterized by progressive loss in synaptic function, notable bioenergetic decline, increased neuronal death and brain atrophy, and significant cognitive *** the etiology of LOAD remains unknown, a treatment for LOAD has not yet been formulated, a fact that is clearly demonstrated by the more than 200 failed clinical trials.

关键词： clusterin Alzheimer atrophy

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clusterin transduces Alzheimer-risk signals to amyloidogenesis

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3658-3661页

作者： Xi Liu Rongbo Che Wenping Liang Yun Zhang Liyong Wu Chao Han Hong Lu Weihong Song Yili Wu Zhe Wang The National Clinical Research Center for Geriatric Disease Department of NeurologyAdvanced Innovation Center for Human Brain ProtectionXuanwu HospitalCapital Medical UniversityBeijingPR China Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanPR China Department of Psychiatry Shandong Collaborative Innovation Center for DiagnosisTreatment&Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandongPR China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and The Affiliated Wenzhou Kangning HospitalWenzhou Medical UniversityWenzhouZhejiangPR China

Dear Editor,Deposition of amyloid-β(Aβ)to form neuritic plaque(NP)is the hallmark of Alzheimer’s Disease(AD).Major non-genetic risk factors such as ageing,stroke,diabetes and other conditions facilitate AD pathogenesis via unclear ***,the mechanism underlying NP formation is *** Aβcauses NP in familial AD patients and in transgenic AD mice robustly expressing Aβ,but the NP formation requires long-term Aβaccumulation.

关键词： Alzheimer Aβ clusterin

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clusterin:Review of research progress and looking ahead to direction in hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第27期21卷 8262-8270页

作者： Peng Xiu Xiao-Feng Dong Xin-Ping Li Jie Li Department of General Surgery Shandong Provincial Qianfoshan Hospital Shandong University Department of Hepatobiliary Surgery The People’s Hospital of Guangxi Zhuang Autonomous Region

Liver cancer, a large proportion of which is hepatocellular carcinoma(HCC), is diagnosed in more than 700000 people each year worldwide. Liver cancer is particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where hepatitis B and hepatitis C infection rates are very high. However, due to resistance to chemotherapy, patients with intermediate and advanced-stage disease cannot benefit from this treatment. clusterin, which is overexpressed in many different cancers, is a stress-induced cytoprotective protein that confers treatment resistance. Custirsen(OGX-011) is a novel 2'-methoxyethyl modified phosphorothioate antisense oligonucleotide that targets secretory clusterin protein expression and is currently in clinical trials for patients with different cancers. In recent years, a number of different clinical trials have been performed, and two phase Ⅲ clinical trials of custirsen evaluating combinations with chemotherapy in patients with metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer are currently in progress. The aims of this review are to summarize the current state of research on clusterin, predict future research directions and analyze the potential of the clinical application of custirsen in HCC.

关键词： Hepatocellular carcinoma clusterin Custirsen Chemotherapy Antisense oligonucleotides

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Induction of clusterin Expression by Neuronal Cell Death in Zebrafish

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Journal of Genetics and Genomics 2014年第11期41卷 583-589页

作者： Yun-Mi Jeong Tae-Eun Jin Jung-Hwa Choi Mi-Sun Lee Hyun-Taek Kim Kyu-Seok Hwang Doo-Sang Park Hyun-Woo Oh Joong-Kook Choi Vladimir Korzh Melitta Schachner Kwan-Hee You Cheol-Hee Kim Department of Biology Chungnam National University Korea Research Institute of Bioscience and Biotechnology Department of Biochemistry College of MedicineChungbuk National University Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience Rutgers University Center for Neuroscience Shantou University Medical College

clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of- function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general. Zebrafish was investigated as a model system to study human diseases. During development, zebrafish clusterin was expressed in the notochord and nervous system. Embryonic overexpression of clusterin by mRNA microinjection did not affect axis formation, whereas its knock-down by anti-sense morpholino treatment resulted in neuronal cell death. To analyze the function of clusterin in neurodegeneration, a transgenic zebrafish was investigated, in which nitroreductase expression is regulated under the control of a neuron-specifc huC promoter which is active between the stages of early neuronal precursors and mature neurons. Nitroreductase turns metronidazole into a cytotoxic agent that induces cell death within 12 h. After metronidazole treatment, transgenic zebrafish showed neuron-specific cell death. Interestingly, we also observed a dramatic induction of clusterin expression in the brain and spinal cord in these fish, suggesting a direct or indirect role of clusterin in neuronal cell death and thus, more generally, in neurodegeneration.

关键词： clusterin Neuronal cell death Neurodegeneration Zebrafish

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Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression

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World Journal of Gastroenterology 2005年第21期11卷 3285-3289页

作者： DanXie JonathanS.T.Sham Wei-FenZeng Li-HongChe MengZhang Hui-XiWu Han-LiangLin Jian-MingWen SzeHangLau LiangHu Xin-YuanGuan DepartmentofPathology ZhongShanMedicalCollegeSunYat-SenUniversityGuangzhou510089GuangdongProvinceChina DepartmentofClinicalOncology TheUniversityofHongKongHongKongChina

AIM: To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series,and to explore the potential role of clusterin in multistage colorectal tumorigenesis and progression. METHODS: A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B,21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohist-ochemistry and TUNEL assay,*** the potential correlation of dusterin expression with the patient's clinical-pathological features were also examined. RESULTS: The positive staining of clusterin in different colorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal colorectal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (Pclusterin in CRCs was inversely correlated with tumor apoptotic index (Pclusterin in CRCs. CONCLUSION:These data suggests that overexpression of cytoplasmic dusterin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic dusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.

关键词： clusterin Colorectal tumorigenesis

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Metformin targets clusterin to control lipogenesis and inhibit the growth of bladder cancer cells through SREBP-lc/FASN axis

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1092-1094页

作者： Jun Deng Mei Peng Sichun Zhou Di Xiao Xin Hu Simeng Xu Jingtao Wu Xiaoping Yang Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province Department of Pharmacy School of MedicineHunan Normal UniversityChangsha 410013China Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University) Ministry of EducationYantai UniversityYantai 264005China Department of Pharmacy Xiangyo HospitalCentral South UniversityChangsha 410008China

Dear Editor,Metformin,a widely prescribed drug for treating typeⅡdiabetes,has shown an important anti-cancer property.1 However,new launched clinical trials did not achieve such desirable results.2 One explanation could be that metformin’s anti-cancer mechan-isms and precise therapeutic targets remain *** identify potential therapeutic targets of metformin in bladder cancer,we screened differential proteins with metformin treatment in T24 cells by high-throughput protein chip.

关键词： bladder cancer clusterin

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clusterin as a serum biomarker candidate contributes to the lung fibroblasts activation in chronic obstructive pulmonary disease

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Chinese Medical Journal 2022年第9期135卷 1076-1086页

作者： Qiang Zhang Yuanyi Yue Rui Zheng Department of Pulmonary and Critical Care Medicine Shengjing Hospital of China Medical UniversityShenyangLiaoning 110014China Department of Gastroenterology Medicine Shengjing Hospital of China Medical UniversityShenyangLiaoning 110014China

Background:Fibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease(COPD).However,the key proteins involved in its development are still poorly ***,we aimed to identify the differentially expressed proteins(DEPs)between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung ***:The potential DEPs were identified by isobaric tags for relative and absolute quantitation(iTRAQ)-based proteomic *** messenger RNA and protein levels of clusterin(CLU)in COPD patients and 12%cigarette smoke extract(CSE)-treated human bronchial epithelial cells were determined at the indicated time ***,anin vitro COPD model was established via the administration of 8%CSE to normal human lung fibroblasts(NHLFs)at indicated time *** effects of CSE treatment andCLU silencing on proliferation and activation of lung fibroblasts were ***:A total of 144 DEPs were identified between COPD patients and normal *** iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker *** also discovered that CLU levels were significantly increased(P<0.0001)in Global Initiative for Obstructive Lung Disease II,III,and IV patients and correlated(P<0.0001)with forced expiratory volume in 1 s(R=-0.7705),residual volume(RV)(R=0.6281),RV/total lung capacity(R=0.5454),and computerized tomography emphysema(R=0.7878).Similarly,CLU levels were significantly increased in CSE-treated cells at indicated time points(P<0.0001).The CSE treatment significantly inhibited the proliferation,promoted the inflammatory response,differentiation of NHLFs,and collagen matrix deposition,and induced the apoptosis of NHLFs;however,these effects were partially reversed byCLU ***:Our findings suggest that CLU may play significant roles during ai

关键词： Chronic obstructive pulmonary disease clusterin Cigarette smoke extract Airway fibrosis Lung fibroblasts

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clusterin在恶性肿瘤治疗中的研究进展

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肿瘤 2013年第4期33卷 368-371页

作者：马晓李鹤成复旦大学附属肿瘤医院胸外科复旦大学上海医学院肿瘤学系上海200032

CLU(clusterin)是一种广泛存在于人体组织和体液中的凋亡相关蛋白,在多种病理、生理过程(包括组织重构、再生、脂质转运、补体调节和细胞凋亡等)中发挥重要作用。研究发现,CLU在正常的成熟组织中低表达,而选择性地在某些恶性肿瘤中高表... 详细信息

CLU(clusterin)是一种广泛存在于人体组织和体液中的凋亡相关蛋白,在多种病理、生理过程(包括组织重构、再生、脂质转运、补体调节和细胞凋亡等)中发挥重要作用。研究发现,CLU在正常的成熟组织中低表达,而选择性地在某些恶性肿瘤中高表达。CLU有2种主要亚型:分泌型CLU和核型CLU,它们在人类恶性肿瘤中发挥不同的作用。在恶性肿瘤治疗中,以CLU为靶点的研究已逐步展开。

关键词：肿瘤治疗凋亡调节蛋白质类 clusterin

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