Reduction of Potassium Currents and Phosphatidylinositol 3- Kinase-Dependent Akt Phosphorylation by Tumor Necrosis Factor-a Rescues Axotomized Retinal Ganglion Cells from Retrograde Cell Death In Vivo
نویسندگان
چکیده
Tumor-necrosis-factor-a (TNF-a) 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-a decreased outward potassium currents in RGCs. Antagonism of the TNF-a-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-a-induced potassium current reduction. Inhibition of the phosphatidylinositol 3-kinase–Akt pathway with wortmannin decreased TNF-a-promoted RGC survival. These data point to a functionally relevant cytokine-dependent neuroprotective signaling cascade in adult CNS neurons.
منابع مشابه
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