title: A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death.
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)-alpha-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.
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tokita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kakizawa
authors.forename: Michiru
authors.initials: M
authors.lastname: Ida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Fumiko
authors.initials: F
authors.lastname: Matsui
authors.forename: Sachiko
authors.initials: S
authors.lastname: Aono
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Oohira
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000633:toxicity; D019579:Neocortex / Q000166:cytology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D010766:Phosphorylation; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D053148:Caspase 3; D002809:Chondroitin Sulfates; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D009498:Neurotoxins; D000071228:Polyelectrolytes; D011108:Polymers; D014443:Tyrosine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C505410:Casp3 protein, rat