肿瘤坏死因子-α降低钾电流和磷脂酰肌醇3激酶依赖性AKT磷酸化可挽救体内轴突切断的视网膜神经节细胞免于逆行性细胞死亡。
Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent AKT phosphorylation by tumor necrosis factor-(alpha) rescues axotomized retinal ganglion cells from retrograde cell death in vivo.
作者信息
Diem R, Meyer R, Weishaupt J H, Bahr M
机构信息
Neurologische Universitätsklinik, 72076 Tübingen, Germany.
出版信息
J Neurosci. 2001 Mar 15;21(6):2058-66. doi: 10.1523/JNEUROSCI.21-06-02058.2001.
Abstract
Tumor-necrosis-factor-alpha (TNF-alpha) prevented secondary death of retinal ganglion cells (RGCs) after axotomy of the optic nerve in vivo. This RGC rescue was confirmed in vitro in a mixed retinal culture model. In accordance with our previous findings, TNF-alpha decreased outward potassium currents in RGCs. Antagonism of the TNF-alpha-induced decrease in outward potassium currents with the potassium channel opener minoxidilsulfate (as verified by electrophysiology) abolished neuroprotection. Western blot analysis revealed an upregulation of phospho-Akt as a consequence of TNF-alpha-induced potassium current reduction. Inhibition of the phosphatidylinositol 3-kinase-Akt pathway with wortmannin decreased TNF-alpha-promoted RGC survival. These data point to a functionally relevant cytokine-dependent neuroprotective signaling cascade in adult CNS neurons.
摘要
肿瘤坏死因子-α（TNF-α）可预防体内视神经切断术后视网膜神经节细胞（RGC）的继发性死亡。在混合视网膜培养模型中，体外实验证实了TNF-α对RGC的这种挽救作用。与我们之前的研究结果一致，TNF-α降低了RGC的外向钾电流。用钾通道开放剂硫酸米诺地尔拮抗TNF-α诱导的外向钾电流降低（通过电生理学验证）可消除神经保护作用。蛋白质印迹分析显示，TNF-α诱导的钾电流减少导致磷酸化Akt上调。用渥曼青霉素抑制磷脂酰肌醇3-激酶-Akt通路可降低TNF-α促进的RGC存活。这些数据表明，在成体中枢神经系统神经元中存在功能相关的细胞因子依赖性神经保护信号级联反应。
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