title: A highly-sulfated chondroitin sulfate, CS-E, adsorbs specifically to neurons with nuclear condensation.
abstract: A highly sulfated chondroitin sulfate, CS-E, prevents excitatory amino acid-induced neuronal cell death by an as yet unknown mechanism. To reveal this mechanism, we pretreated neurons in culture with various inhibitors, and examined whether N-methyl-D-aspartic acid (NMDA)-induced neuronal cell death was reduced in the presence of CS-E. The inhibitors of protein kinase C (PKC) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) ameliorated NMDA-induced neuronal cell death, but did not affect the neuroprotective activity of CS-E. Among the growth factors with which CS-E can interact, high concentration of BDNF protected against the NMDA-induced neuronal cell death and strengthened neuroprotection by CS-E. CS-E, but neither CS-A nor CS-C, adsorbed to a subclass of neurons with nuclear condensation, namely pyknosis. Contactin-1 (CNTN-1), a putative receptor for neuritogenic activity of CS-E, was present in cortical neurons, but a neutralizing antibody to CNTN-1 did not block neuroprotective activity of CS-E. The results suggest that CS-E may prevent the progression of cell death at the early stages of excitotoxicity through a signaling pathway different from CNTN-1.
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya-cho, Kasugai, Aichi 480-0392, Japan. nakanishi@inst-hsc.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Miharu
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Oohira
mesh_terms: D000327:Adsorption; D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus; D002809:Chondroitin Sulfates / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002809:Chondroitin Sulfates