A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death
A highly sulfated chondroitin sulfate preparation, CS-E, prevents excitatory amino acid-induced neuronal cell death
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DOI：
10.1111/j.1471-4159.2007.05107.x
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发表时间：
2008-03-01
影响因子：
4.7
通讯作者：
Oohira, Atsuhiko
中科院分区：
文献类型：
--
作者：
Sato, Yoshiaki;Nakanishi, Keiko;Oohira, Atsuhiko
硫酸软骨素（CS）是中枢神经系统的主要微环境分子，其神经保护作用的研究报道较少。由于兴奋性毒性引起的神经元细胞死亡是许多神经元疾病的关键阶段，我们研究了各种CS制剂对谷氨酸类似物兴奋性毒性诱导的神经元细胞死亡的影响。CS制剂被添加到培养的神经元之前和之后的谷氨酸类似物的管理。然后，估计神经元细胞死亡和存活的程度。预先给予高度硫酸化的CS制剂CS-E，不仅显著降低了NMDA诱导的神经元细胞死亡，而且显著降低了（S）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸或红藻氨酸诱导的神经元细胞死亡。除了CS-E之外，CS制剂和其他高度硫酸化的多糖（如肝素和硫酸葡聚糖）都没有产生任何神经保护作用。预先给予CS-E不改变NMDA诱导的神经元电流，但改变了蛋白酪氨酸磷酸化的模式。此外，在CS-E处理的神经元中，caspase 3活性的升高被显著抑制。这些结果表明，CS-E防止各种谷氨酸受体介导的神经元细胞死亡，并表明磷酸化相关的细胞内信号和caspase 3激活的抑制与CS-E的神经保护有关。
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.