Zebrafish High-Throughput Screening to Study the Impact of Dissolvable Metal Oxide Nanoparticles on the Hatching Enzyme, ZHE1

Authors

  • Sijie Lin,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Yan Zhao,

    1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, USA,
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  • Zhaoxia Ji,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Jason Ear,

    1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, USA,
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  • Chong Hyun Chang,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Haiyuan Zhang,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Cecile Low-Kam,

    1. Department of Biostatistics, University of California, Los Angeles, USA
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  • Kristin Yamada,

    1. Department of Environmental Health Sciences, University of California, Los Angeles, USA
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  • Huan Meng,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
    2. Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, USA
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  • Xiang Wang,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Rong Liu,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
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  • Suman Pokhrel,

    1. IWT Foundation Institute of Materials Science, Department of Production Engineering, University of Bremen, Germany
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  • Lutz Mädler,

    1. IWT Foundation Institute of Materials Science, Department of Production Engineering, University of Bremen, Germany
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  • Robert Damoiseaux,

    1. Molecular Shared Screening Resources, California NanoSystem Institute, University of California, Los Angeles, USA
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  • Tian Xia,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
    2. Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, USA
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  • Hilary A. Godwin,

    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
    2. Department of Environmental Health Sciences, University of California, Los Angeles, USA
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  • Shuo Lin,

    1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, USA,
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  • André E. Nel

    Corresponding author
    1. Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107
    2. Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, USA
    • Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, USA, Tel: (310) 825-6620, Fax: (310) 206-8107.
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Abstract

The zebrafish is emerging as a model organism for the safety assessment and hazard ranking of engineered nanomaterials. In this Communication, the implementation of a roboticized high-throughput screening (HTS) platform with automated image analysis is demonstrated to assess the impact of dissolvable oxide nanoparticles on embryo hatching. It is further demonstrated that this hatching interference is mechanistically linked to an effect on the metalloprotease, ZHE 1, which is responsible for degradation of the chorionic membrane. The data indicate that 4 of 24 metal oxide nanoparticles (CuO, ZnO, Cr2O3, and NiO) could interfere with embryo hatching by a chelator-sensitive mechanism that involves ligation of critical histidines in the ZHE1 center by the shed metal ions. A recombinant ZHE1 enzymatic assay is established to demonstrate that the dialysates from the same materials responsible for hatching interference also inhibit ZHE1 activity in a dose-dependent fashion. A peptide-based BLAST search identifies several additional aquatic species that express enzymes with homologous histidine-based catalytic centers, suggesting that the ZHE1 mechanistic paradigm could be used to predict the toxicity of a large number of oxide nanoparticles that pose a hazard to aquatic species.

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