Department of Pharmacology and Neuroscience, Texas Tech University Health Science Center, Lubbock, TX, USA.
Environ Toxicol Pharmacol. 2012 Mar;33(2):353-60. doi: 10.1016/j.etap.2011.12.027. Epub 2012 Jan 8.
Primary cultures of fetal rat cortical neurons and astrocytes were used to test the hypothesis that astrocyte-mediated control of neuronal glutathione (GSH) is a potent factor in neuroprotection against rotenone and paraquat. In neurons, rotenone (0.025-1 μM) for 4 and 24 h decreased viability as did paraquat (2-100 μM). Rotenone (30 nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30 μM) decreased neuronal viability and GSH by 36% and 70%, while ROS were increased by 23%. When neurons were co-cultured with astrocytes, their GSH increased 1.5 fold and 5 fold at 12 and 24 h. Co-culturing with astrocytes blocked neuronal death and damage by rotenone and paraquat. Astrocyte-mediated neuroprotection was dependent on the activity of components of the γ-glutamyl cycle. These studies illustrate the importance of astrocyte-mediated glutathione homeostasis for protection of neurons from rotenone and paraquat and the role of the γ-glutamyl cycle in this neuroprotection.
原代培养的胎鼠皮质神经元和星形胶质细胞被用于检验以下假说，即星形胶质细胞介导的神经元谷胱甘肽（GSH）控制是对抗鱼藤酮和百草枯神经保护的一个重要因素。在神经元中，鱼藤酮（0.025-1 μM）处理 4 和 24 小时可降低细胞活力，百草枯（2-100 μM）也是如此。鱼藤酮（30 nM）使神经元活力和 GSH 分别降低 24%和 30%，同时 ROS 增加 56%。百草枯（30 μM）使神经元活力和 GSH 分别降低 36%和 70%，同时 ROS 增加 23%。当神经元与星形胶质细胞共培养时，其 GSH 在 12 小时和 24 小时分别增加了 1.5 倍和 5 倍。与星形胶质细胞共培养可阻止鱼藤酮和百草枯引起的神经元死亡和损伤。星形胶质细胞介导的神经保护作用依赖于γ-谷氨酰循环的组成部分的活性。这些研究说明了星形胶质细胞介导的谷胱甘肽动态平衡对保护神经元免受鱼藤酮和百草枯的重要性，以及γ-谷氨酰循环在这种神经保护中的作用。
