A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death.
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.
Sato
Yoshiaki
Y
Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
Nakanishi
Keiko
K
Tokita
Yoshihito
Y
Kakizawa
Hiroko
H
Ida
Michiru
M
Maeda
Hiroshi
H
Matsui
Fumiko
F
Aono
Sachiko
S
Saito
Akiko
A
Kuroda
Yoshiyuki
Y
Hayakawa
Masahiro
M
Kojima
Seiji
S
Oohira
Atsuhiko
A
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
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