Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina
Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina
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DOI：
10.1002/jnr.20786
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发表时间：
2006-04-01
影响因子：
4.2
通讯作者：
Ueno, S
中科院分区：
文献类型：
--
作者：
Munemasa, Y;Ohtani-kaneko, R;Ueno, S
我们研究了c-Jun对N-甲基-D-天冬氨酸（NMDA）诱导的大鼠视网膜神经毒性的作用。在玻璃体内注射NMDA（20 nmol）后3 h检测到视网膜中c-Jun mRNA、c-Jun蛋白和磷酸化c-Jun（p-c-Jun）水平的增加。注射NMDA后12小时，c-Jun和p-c-Jun免疫反应在视网膜神经节细胞层（RGCL），尤其是视网膜神经节细胞（RGCs）和内核层（INL）中观察到，末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）阳性细胞对c-Jun和p-c-Jun呈免疫阳性。其与NMDA同时注射，穿透RGCL和INL中的细胞，抑制NMDA诱导的c-Jun和p-c-Jun蛋白水平的增加，并且在注射后12小时减少RGCL中TUNEL阳性细胞的数目。c-Jun AS ODN对NMDA处理的视网膜的保护作用也通过RGCL细胞计数和IPL厚度的测量以及通过注射后7天的Thy-1 mRNA的定量实时PCR分析来显示。这些结果表明，c-Jun的合成和磷酸化参与NMDA诱导的神经元细胞死亡。(C)2006 Wiley-Liss，Inc.
We examined the role of c-Jun on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. An increase in c-Jun mRNA, c-Jun protein and phosphorylated c-Jun (p-c-Jun) levels in the retina was detected 3 hr after intravitreal injection of NMDA (20 nmol). These levels peaked after 12 hr, and then returned to their control levels by 24 hr. c-Jun and p-c-Jun immunoreactivities were observed in the retinal ganglion cell layer (RGCL), especially in retinal ganglion cells (RGCs), and in the inner nuclear layer (INL) 12 hr after NMDA injection, and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive cells were immunopositive for c-Jun and p-c-Jun. A c-Jun antisense oligodeoxynucleotide (AS ODN), which was simultaneously injected with NMDA, penetrated the cells in the RGCL and the INL, suppressed the NMDA-induced increase in c-Jun and p-c-Jun protein levels and reduced the number of TUNEL-positive cells in the RGCL 12 hr after the injection. The protective effect of c-Jun AS ODN on the NMDA-treated retina was also shown by the RGCL cell count and measurement of the IPL thickness, as well as by quantitative real-time PCR analysis of Thy-1 mRNA 7 days after the injection. These results suggest that c-Jun synthesis and phosphorylation participate in NMDA-induced neuronal cell death. (C) 2006 Wiley-Liss, Inc.