title: Induction of clusterin expression by neuronal cell death in Zebrafish.
abstract: 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-specific 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.
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Jeong
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors.forename: Tae-Eun
authors.initials: TE
authors.lastname: Jin
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Kyu-Seok
authors.initials: KS
authors.lastname: Hwang
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors.forename: Doo-Sang
authors.initials: DS
authors.lastname: Park
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Oh
authors.affiliation: Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
authors.affiliation: Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Korzh
authors.affiliation: Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA; Center for Neuroscience, Shantou University Medical College, Shantou 515041, China. Electronic address: Schachner@biology.rutgers.edu.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: khyou@cnu.ac.kr.
authors.forename: Kwan-Hee
authors.initials: KH
authors.lastname: You
authors.affiliation: Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: zebrakim@cnu.ac.kr.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D016923:Cell Death; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D051152:Clusterin / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009672:Notochord / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D051152:Clusterin; D029961:Zebrafish Proteins
keywords: Clusterin; Neurodegeneration; Neuronal cell death; Zebrafish