A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death

Authors

  • Yoshiaki Sato,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
    2. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
    3. Department of Neonatology, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Keiko Nakanishi,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Yoshihito Tokita,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Hiroko Kakizawa,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
    2. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Michiru Ida,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Hiroshi Maeda,

    1. Central Research Laboratories, Seikagaku Corporation., Higashiyamato, Tokyo, Japan
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  • Fumiko Matsui,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Sachiko Aono,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Akiko Saito,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
    2. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
    3. Department of Neonatology, Central Hospital, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Yoshiyuki Kuroda,

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Masahiro Hayakawa,

    1. Maternity and Perinatal Care Center, Nagoya University Hospital, Nagoya, Japan
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  • Seiji Kojima,

    1. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
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  • Atsuhiko Oohira

    1. Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan
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  • Yoshiaki Sato and Keiko Nakanishi contributed equally to this work.

Address correspondence and reprint requests to Atsuhiko Oohira, PhD, Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan. E-mail: atsu48@aichi-med-u.ac.jp

Abstract

J. Neurochem. (2008) 104, 1565–1576.

Abstract

Chondroitin sulfate (CS) is a major microenvironmental molecule in the CNS, and there have been few reports about its neuroprotective activity. As neuronal cell death by excitotoxicity is a crucial phase in many neuronal diseases, we examined the effect of various CS preparations on neuronal cell death induced by the excitotoxicity of glutamate analogs. CS preparations were added to cultured neurons before and after the administration of glutamate analogs. Then, the extents of both neuronal cell death and survival were estimated. Pre-administration of a highly sulfated CS preparation, CS-E, significantly reduced neuronal cell death induced by not only NMDA but also (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainate. Neither CS preparations other than CS-E nor other highly sulfated polysaccharides such as heparin and dextran sulfate exerted any neuroprotective effects. NMDA-induced current in neurons was not changed by pre-administration of CS-E, but the pattern of protein-tyrosine phosphorylation was changed. In addition, the elevation of caspase 3 activity was significantly suppressed in CS-E-treated neurons. These results indicate that CS-E prevents neuronal cell death mediated by various glutamate receptors, and suggest that phosphorylation-related intracellular signals and the suppression of caspase 3 activation are implicated in neuroprotection by CS-E.

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