Synthetic Sialyl Compounds as Well as Natural Gangliosides Induce Neuritogenesis in a Mouse Neuroblastoma Cell Line (Neuro2a)

Authors

  • Shuichi Tsuji,

    1. Department of Biochemistry, Faculty of Medicine, University of Tokyo, Tokyo
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  • Tatsuro Yamashita,

    1. Department of Biochemistry, Faculty of Medicine, University of Tokyo, Tokyo
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  • Makoto Tanaka,

    1. Department of Biochemistry, Faculty of Medicine, University of Tokyo, Tokyo
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  • Yoshitaka Nagai

    Corresponding author
    1. Department of Biochemistry, Faculty of Medicine, University of Tokyo, Tokyo
    2. Department of Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan
      Address correspondence and reprint requests to Dr. Y. Nagai al Department of Biochemistry. Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.
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Address correspondence and reprint requests to Dr. Y. Nagai al Department of Biochemistry. Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan.

Abstract

Amphipathic compounds containing N-acetylneuraminic acid (sialic acid) [for example, D-N-acetylneuraminyl-(α2-1)-2S, 3R,4E-2-N-tetracosanoyl sphingenine, sialyl alkyl glycerol ethers, and sialyl cholesterols] induced neuritogenesis in a neuroblastoma cell line (Neuro2a). The sialic acid in the hydrophilic moiety of the compounds is specifically required for neuritogenesis. The requirement for molecular specificity of the hydrophobic moiety, however, is rather low. Regarding the hydrophobic moiety, no preference for cholesterol, alkyl glycerol ether, or ceramide residues was observed as to their neuritogenic activity. Sialyl compounds with α-ketosidic sialyl linkages were more active than the corresponding β-anomers. These sialyl compounds induced the growth of only one neurite, but a long one, from the cell body. This type of neuritogenesis is completely different from that induced by compounds capable of elevating the concentration of intracellular cyclic AMP, which induced the appearance of many neurites from a single cell body. Besides this morphological change, the active sialyl compounds also caused a change in the carbohydrate composition of the cell surface. Sialyl compound treatment drastically increased the concentration of peanut agglutinin binding sites.

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