Reduction of potassium currents and phosphatidylinositol 3-kinase-dependent Akt phosphorylation by tumor necrosis factor-α rescues axotomized retinal ganglion cells from retrograde cell death in vivo

被引:125
作者
Diem, R [1 ]
Meyer, R [1 ]
Weishaupt, JH [1 ]
Bähr, M [1 ]
机构
[1] Univ Tubingen, Neurol Klin, D-72076 Tubingen, Germany
关键词
tumor necrosis factor-alpha; retinal ganglion cells; neuroprotection; outward potassium current; PKB/Akt; PI3-K; retrograde cell death;
D O I
10.1523/JNEUROSCI.21-06-02058.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:2058 / 2066
页数:9
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