Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death.
Astrocytes protect neurons from ethanol-induced oxidative stress and apoptotic death.
复制标题
星形胶质细胞保护神经元免受乙醇诱导的氧化应激和细胞凋亡。
DOI：
10.1002/jnr.20502
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Henderson,GeorgeI
中科院分区：
文献类型：
--
作者：
Watts,LoraTalley;Rathinam,MaryLatha;Schenker,Steven;Henderson,GeorgeI
乙醇会在培养的胎鼠皮层神经元中诱导氧化应激，随后导致细胞凋亡，可以通过还原型谷胱甘肽 (GSH) 细胞含量正常化来预防细胞凋亡。由于星形胶质细胞在维持神经元 GSH 稳态中发挥核心作用，因此以下实验利用新生大鼠皮质星形胶质细胞和胎儿皮质神经元的共培养来确定星形胶质细胞是否可以通过这种机制保护神经元免受乙醇介导的细胞凋亡。在缺乏星形胶质细胞培养的皮层神经元中，乙醇（2.5 和 4 mg/ml；暴露 6、12 和 24 小时）使台盼蓝排除和 MTT 活力测量降低高达 45%（P<0.05），使活性氧 (ROS) 水平增加高达 81%（P<0.05），并在治疗 1 小时内使 GSH 降低 49% 和2.5 和 4 mg/ml 分别为 51%（P<0.05）。随后细胞凋亡开始死亡，通过暴露于乙醇 12 小时后膜联蛋白 V 结合增加和 DNA 片段化来确定。神经元与星形胶质细胞共培养可通过 2.5 mg/ml 乙醇防止 GSH 消耗，而暴露于 4 mg/ml 乙醇的神经元中 GSH 含量比对照增加（高达 341%；P< 0.05）。乙醇会增加神经元活性氧和细胞凋亡；共培养也可以防止活力下降。使用相同的方法，星形胶质细胞对乙醇基本上不敏感。仅暴露于 4.0 mg/ml 乙醇就会降低星形胶质细胞中的 GSH 含量，同时 GSH 流出量增加 204%（P < 0.05）。这些研究表明星形胶质细胞可以保护神经元免受乙醇介导的细胞凋亡，这可能与神经元谷胱甘肽的维持有关。 © 2005 Wiley-Liss, Inc.
Ethanol induces oxidative stress in cultured fetal rat cortical neurons and this is followed by apoptotic death, which can be prevented by normalization of cell content of reduced glutathione (GSH). Because astrocytes can play a central role in maintenance of neuron GSH homeostasis, the following experiments utilized cocultures of neonatal rat cortical astrocytes and fetal cortical neurons to determine if astrocytes could protect neurons from ethanol‐mediated apoptotic death via this mechanism. In cortical neurons cultured in the absence of astrocytes, ethanol (2.5 and 4 mg/ml; 6‐, 12‐, and 24‐hr exposures) decreased trypan blue exclusion and the MTT viability measures by up to 45% (P< 0.05), increased levels of reactive oxygen species (ROS) by up to 81% (P< 0.05), and decreased GSH within 1 hr of treatment by 49 and 51% for 2.5 and 4 mg/ml, respectively (P< 0.05). This was followed by onset of apoptotic cell death as determined by increased Annexin V binding and DNA fragmentation by 12 hr of ethanol exposure. Coculturing neurons with astrocytes prevented GSH depletion by 2.5 mg/ml ethanol, whereas GSH content was increased over controls in neurons exposed to 4 mg/ml ethanol (by up to 341%;P< 0.05). Ethanol generated increases in neuron ROS and apoptosis; decreases in viability were also prevented by coculture. Astrocytes were largely insensitive to ethanol, using the same measures. Only exposure to 4.0 mg/ml ethanol decreased GSH content in astrocytes, concomitant with a 204% increase in GSH efflux (P< 0.05). These studies illustrate that astrocytes can protect neurons from ethanol‐mediated apoptotic death and that this may be related to maintenance of neuron GSH. © 2005 Wiley‐Liss, Inc.