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

来源：

JOURNAL OF NEUROSCIENCE | 2001年 / 21卷 / 06期

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

页码：2058 / 2066

页数：9

共 72 条

[51] Depolarization and cAMP elevation rapidly recruit TrkB to the plasma membrane of CNS neurons [J].