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Complestatin Antagonizes the AMPA/Kainate-Induced Neurotoxicity in Cultured Chick Telencephalic Neurons

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Abstract

Excitatory amino acids are known to induce considerable neurotoxicity in central nervous system. In the present study, the neurotoxicity was induced by application of kainate or AMPA in chick telencephalic neuron, and neuroprotective activity was tested with complestatin that was isolated from streptomyces species. In cultured telencephalic neurons exposed to 500 μM kainate for 2 days, the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 5 μM) completely blocked kainate-induced neurotoxicity. Also, complestatin (0.5 μM) completely blocked kainate-induced neuronal injury at a concentration lower than that required for prototype AMPA/kainate receptor antagonist DNQX. In addition, complestatin blocked AMPA-induced neurotoxicity when the neurons were pretreated with cyclothiazide, a desensitization blocker of AMPA receptor. Surprisingly, when the onset of the treatment was delayed for 6 hours, complestatin led to a reduction in kainate-induced neuronal injury. While inhibition of protein kinase C (PKC) by staurosporin induced neurotoxicity, that was blocked by complestatin. Activation of PKC by phorbol dibutyrate partially inhibited the kainate-induced neurotoxicity. These results suggest that complestatin may be used as an anti-excitotoxic agent and involved in the PKC activation contributing to inhibition of neurotoxicity.

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Authors and Affiliations

  1. Antibiotics Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea

    Ick Dong Yoo, Bong Sik Yun & In Ja Ryoo

  2. Center for Cell Signaling Research, Division of Molecular Life Science, Ewha Womans University, Seoul, Korea

    Soo Young Lee

  3. Department of Parasitology, College of Medicine, Yonsei University, Seoul, Korea

    Myeong Heon Shin

  4. Department of Neuroscience and Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea

    Seikwan Oh

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  1. Ick Dong Yoo
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Yoo, I.D., Yun, B.S., Ryoo, I.J. et al. Complestatin Antagonizes the AMPA/Kainate-Induced Neurotoxicity in Cultured Chick Telencephalic Neurons. Neurochem Res 27, 337–343 (2002). https://doi.org/10.1023/A:1014919531306

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