17β-estradiol prevents reduction of retinal phosphorylated 14-3-3 zeta protein levels following a neurotoxic insult
17β-estradiol prevents reduction of retinal phosphorylated 14-3-3 zeta protein levels following a neurotoxic insult
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DOI：
10.1016/j.brainres.2011.11.034
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发表时间：
2012-01-18
期刊：
影响因子：
2.9
通讯作者：
Ohtani-Kaneko, Ritsuko
中科院分区：
文献类型：
--
作者：
Koseki, Natsuko;Kitaoka, Yasushi;Ohtani-Kaneko, Ritsuko
以往的研究表明，17β-雌二醇(E2)对几种类型的神经元具有重要的保护作用，但其作用机制尚不清楚。在本研究中，我们发现玻璃体内注射N-甲基-D-天冬氨酸(NMDA)后，大鼠视网膜中14-3-3Zeta基因的表达水平以及14-3-3Zeta蛋白的磷酸化和总水平显著降低。17β-E_2植入可显著抑制NMDA诱导的视网膜磷酸化水平的下降，但不能抑制14-3-3-3Zeta蛋白总量的下降。视网膜神经节细胞系RGC-5细胞在谷氨酸和丁硫氨酸亚磺胺(BSO)作用后，磷酸化的14-3-3蛋白水平和总的14-3-3蛋白水平均下降，17β-E2处理组仅抑制磷酸化水平的下降，而不抑制总的14-3-3 Zeta蛋白水平的下降。细胞活力测定显示，谷氨酸和BSO暴露后细胞大量死亡，17β-E2处理可显著保护这种细胞死亡。17β-E_2处理组的RGC-5细胞磷酸化14-3-3蛋白水平也显著高于对照组。这些结果提示，14-3-3Zeta表达的降低可能与NMDA或谷氨酸和BSO联合作用所致的视网膜神经毒性有关。调节14-3-3-Zeta的磷酸化是17β-E2保护视网膜的可能机制之一。(C)2011爱思唯尔B.V.保留所有权利。
Previous studies demonstrated the substantial protective role of 17 beta-estradiol (E2) in several types of neuron, although its mechanism of action remains to be elucidated. In this study, we found that the levels of 14-3-3 zeta mRNA and phosphorylated and total 14-3-3 zeta proteins were significantly decreased in the rat retina after intravitreal injection of N-methyl-D-aspartate (NMDA). 17 beta-E2 implantation significantly inhibited NMDA-induced decreases in phosphorylated but not in total 14-3-3 zeta protein levels in the retina. There was a decrease in both phosphorylated and total 14-3-3 protein levels in RGC-5 cells, a retinal ganglion cell line, after glutamate and buthionine sulfoximine (BSO) exposure, and 17 beta-E2 treatment significantly inhibited only the decrease in phosphorylated but not in total 14-3-3 zeta protein levels. The cell viability assay showed substantial cell death after glutamate and BSO exposure and that 17 beta-E2 treatment significantly protects against this cell death. 17 beta-E2 treatment also significantly increased the level of phosphorylated 14-3-3 protein in RGC-5 cells without other treatments. These results suggest that a decrease in 14-3-3 zeta expression may be associated with retinal neurotoxicity induced by NMDA or the combination of glutamate and BSO. The regulation of 14-3-3 zeta phosphorylation is one possible mechanism of the protective effect of 17 beta-E2 in the retina. (C) 2011 Elsevier B.V. All rights reserved.