NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153
NMDA-induced retinal injury is mediated by an endoplasmic reticulum stress-related protein, CHOP/GADD153
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DOI：
10.1111/j.1471-4159.2005.03502.x
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发表时间：
2006-01-01
影响因子：
4.7
通讯作者：
Tanihara, H
中科院分区：
文献类型：
--
作者：
Awai, M;Koga, T;Tanihara, H
我们研究了NMDA诱导的小鼠视网膜损伤后内质网应激相关蛋白CHOP/GADD 153的作用。玻璃体内注射NMDA后6 h，视网膜神经节细胞层（GCL）和内核层（INL）可见TUNEL阳性细胞，并逐渐增多，至24 h。实时荧光定量RT-PCR分析显示，注射NMDA后2 h，CHOP mRNA被诱导约3倍。NMDA处理后，GCL细胞中CHOP蛋白的免疫反应性强烈。免疫印迹分析显示，注射NMDA后，视网膜CHOP蛋白表达增加。与野生型小鼠相比，CHOP-/-小鼠对NMDA诱导的视网膜细胞死亡具有更强的抵抗力。在NMDA治疗后7天，CHOP-/-小鼠的内网状层和INL的厚度大于野生型小鼠。NMDA处理后，CHOP-/-小鼠GCL中残留细胞的数量显著高于野生型小鼠。总之，CHOP在NMDA处理的小鼠视网膜中被诱导，并且CHOP-/-小鼠对NMDA诱导的视网膜损伤更有抵抗力，这表明CHOP在NMDA诱导的视网膜细胞死亡中起重要作用。
We investigated the role of an endoplasmic reticulum stress-associated protein, CHOP/GADD153, after NMDA-induced mouse retinal damage. After injection of NMDA into the vitreous, TUNEL-positive cells were detected in the retinal ganglion cell layer (GCL) and inner nuclear layer (INL) at 6 h after NMDA injection, and these gradually increased in number up to 24 h. Analysis by real-time RT-PCR revealed that CHOP mRNA was induced by about 3-fold, at 2 h after NMDA injection. Immunoreactivity for the CHOP protein was intense in cells of the GCL following NMDA treatment. Immunoblot analysis showed that NMDA injection increased the expression of CHOP protein in the retina. Compared with wild-type mice, CHOP-/- mice were more resistant to NMDA-induced retinal cell death as determined by TUNEL assay. At 7 days after NMDA treatment, the thickness of the inner plexiform layer and INL were larger in CHOP-/- mice than in wild-type mice. The number of residual cells in the GCL following NMDA treatment was significantly higher in CHOP-/- mice than in wild-type mice. In conclusion, CHOP is induced in mouse retina by NMDA treatment, and CHOP-/- mice are more resistant to NMDA-induced retinal damage, suggesting that CHOP plays an important role in NMDA-induced retinal cell death.