Induction of clusterin Expression by Neuronal Cell Death in Zebrafish

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 

作者机构：Department of BiologyChungnam National University Korea Research Institute of Bioscience and Biotechnology Department of BiochemistryCollege of MedicineChungbuk National University Institute of Molecular and Cell BiologyAgency for ScienceTechnology and Research Keck Center for Collaborative Neuroscience and Department of Cell Biology and NeuroscienceRutgers University Center for NeuroscienceShantou University Medical College 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2014年第41卷第11期

页      面：583-589页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the research fund of Chungnam National University,Republic of Korea supported by the Li Kashing Foundation at Shantou University Medical College,China 

主　　题：Clusterin Neuronal cell death Neurodegeneration Zebrafish 

摘      要：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.