Liu Zhan, Huang Ying, Liu Lina, Zhang Li
Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Neurosci Lett. 2017 Sep 14;657:199-203. doi: 10.1016/j.neulet.2017.08.017. Epub 2017 Aug 12.
Ischemic neuronal death is presumably caused by glutamate-induced excitotoxicity, in which the increased glutamate release and impaired glutamate reuptake lead to glutamate accumulation. Mechanisms underlying the ischemic deficiency of astrocytic glutamate reuptake remain unclear, which we have studied by analyzing the effect of calmodulin-dependent protein kinase II (CaMK-II) and protein kinase C (PKC) inhibitions on astrocytic glutamate transporter during ischemia. Glutamate transporter current was recorded on the astrocytes in cortical slices. KN-62 (CaMK-II inhibitor) or chelerythrine (PKC inhibitor) partially reverses the ischemic deficiency of astrocytic glutamate transporter. A combined use of PKC and CaMK-II inhibitors synergistically reverses this deficiency. Thus, one of potential therapeutic strategies is to secure the ischemia-induced deficiency of astrocytic glutamate reuptake by inhibiting PKC and CaMK-II.
缺血性神经元死亡可能是由谷氨酸诱导的兴奋性毒性引起的，其中谷氨酸释放增加和谷氨酸再摄取受损导致谷氨酸积累。星形胶质细胞谷氨酸再摄取缺血性缺陷的潜在机制仍不清楚，我们通过分析钙调蛋白依赖性蛋白激酶II（CaMK-II）和蛋白激酶C（PKC）抑制对缺血期间星形胶质细胞谷氨酸转运体的影响进行了研究。在皮质切片的星形胶质细胞上记录谷氨酸转运体电流。KN-62（CaMK-II抑制剂）或白屈菜红碱（PKC抑制剂）可部分逆转星形胶质细胞谷氨酸转运体的缺血性缺陷。PKC和CaMK-II抑制剂联合使用可协同逆转这种缺陷。因此，一种潜在的治疗策略是通过抑制PKC和CaMK-II来确保缺血诱导的星形胶质细胞谷氨酸再摄取缺陷。
