Induction of clusterin Expression by Neuronal Cell Death in Zebrafish

a.
Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea
b.
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea
c.
Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju 361–763, Republic of Korea
d.
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore
e.
Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA
f.
Center for Neuroscience, Shantou University Medical College, Shantou 515041, China

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Corresponding author: E-mail address: Schachner@biology.rutgers.edu (Melitta Schachner); E-mail address: khyou@cnu.ac.kr (Kwan-Hee You); E-mail address: zebrakim@cnu.ac.kr (Cheol-Hee Kim)

These authors contributed equally to this work.

摘要

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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.
- Clusterin /
- Neuronal cell death /
- Neurodegeneration /
- Zebrafish
These authors contributed equally to this work.
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参考文献(39)

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