Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism
Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism
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DOI：
10.1046/j.1471-4159.2001.00374.x
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发表时间：
2001-06-01
影响因子：
4.7
通讯作者：
Swanson, RA
中科院分区：
文献类型：
--
作者：
Chen, YM;Vartiainen, NE;Swanson, RA
一氧化氮（NO）有助于脑缺血和其他条件下的神经元死亡。星形胶质细胞在解剖学上很好地定位以保护神经元免受NO的影响，因为星形胶质细胞过程包围大多数神经元。在这项研究中，星形胶质细胞限制NO神经毒性的能力进行了检查，使用皮质共培养系统。将星形胶质细胞包被的透析膜直接置于神经元培养物的顶部，以在神经元和培养基之间提供可移除的星形胶质细胞层。该系统的效用进行了测试，通过比较神经元死亡产生的谷氨酸，这是迅速清除星形胶质细胞，和N-甲基-D-天冬氨酸（NMDA），这是不是。星形胶质细胞层的存在使谷氨酸的LD增加了约4倍，但对NMDA毒性没有影响。星形胶质细胞对NO供体S-亚硝基-N-乙酰青霉胺和精胺NONOate产生的神经元死亡的影响通过将这些化合物置于含有对照星形胶质细胞层或通过预先暴露于丁硫氨酸亚砜而耗尽谷胱甘肽的星形胶质细胞层的共培养物的培养基中来检查。与谷胱甘肽耗尽的星形胶质细胞培养的神经元在一系列NO供体浓度下表现出细胞死亡的两倍增加。这些结果表明，星形胶质细胞保护神经元从NO毒性谷胱甘肽依赖性机制。
Nitric oxide (NO) contributes to neuronal death in cerebral ischemia and other conditions. Astrocytes are anatomically well positioned to shield neurons from NO because astrocyte processes surround most neurons. In this study, the capacity of astrocytes to limit NO neurotoxicity was examined using a cortical co-culture system. Astrocyte-coated dialysis membranes were placed directly on top of neuronal cultures to provide a removable astrocyte layer between the neurons and the culture medium. The utility of this system was tested by comparing neuronal death produced by glutamate, which is rapidly cleared by astrocytes, and N-methyl-D-aspartate (NMDA), which is not. The presence of an astrocyte layer increased the LD,, for glutamate by approximately four-fold, but had no effect on NMDA toxicity. Astrocyte effects on neuronal death produced by the NO donors S-nitroso-N-acetyl penicillamine and spermine NONOate were examined by placing these compounds into the medium of co-cultures containing either a control astrocyte layer or an astrocyte layer depleted of glutathione by prior exposure to buthionine sulfoximine. Neurons in culture with the glutathione-depleted astrocytes exhibited a two-fold increase in cell death over a range of NO donor concentrations. These findings suggest that astrocytes protect neurons from NO toxicity by a glutathione-dependent mechanism.