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Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: Secure blockade of ischemic neuronal death

Title
Complestatin is a noncompetitive peptide antagonist of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors: Secure blockade of ischemic neuronal death
Authors
Seo, SYYun, BSRyoo, IJChoi, JSJoo, CKChang, SYChung, JMOh, SGwag, BJYoo, ID
Ewha Authors
정준모
SCOPUS Author ID
정준모scopus
Issue Date
2001
Journal Title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN
0022-3565JCR Link
Citation
vol. 299, no. 1, pp. 377 - 384
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Complestatin, a peptide derived from Streptomyces, was found to protect cultured cortical neurons from excitotoxicity induced by N-methyl-D-aspartate (NMDA), alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or kainate. This neuroprotective behavior of complestatin was attributed to a blockade of Ca2+ ion entry and accumulation, after the activation of NMDA and AMPA/kainate receptors. Complestatin reversibly interfered with NMDA- and AMPA-mediated excitatory synaptic transmission. Complestatin also protected cortical neurons from prolonged deprivation of oxygen and glucose, more effectively than combined antagonists of NMDA and AMPA/kainate receptors. Neurotoxicity, evolving within 1 to 2 days after continuous exposure to combined NMDA and AMPA/kainate antagonists, was not observed in cortical cell cultures that were exposed to complestatin. Finally, complestatin dose dependently prevented neuronal death evolving within the inner nuclear and ganglion cell layers, after transient retinal ischemia. We conclude that complestatin possesses novel pharmacological properties that effectively prevent excitotoxicity under certain pathological conditions.
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자연과학대학 > 생명과학전공 > Journal papers
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