Light-induced retinal damage involves tyrosine 33 phosphorylation, mitochondrial and nuclear translocation of WW domain-containing oxidoreductase in vivo
Light-induced retinal damage involves tyrosine 33 phosphorylation, mitochondrial and nuclear translocation of WW domain-containing oxidoreductase in vivo
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DOI：
10.1016/j.neuroscience.2004.07.054
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Chang, NS
中科院分区：
文献类型：
--
作者：
Chen, ST;Chuang, JI;Chang, NS
含有WW结构域的氧化还原酶WOX1，也被称为WWOX或FOR，是一种已知的促凋亡蛋白和候选肿瘤抑制因子。体外应激刺激通过酪氨酸33 （Tyr33）磷酸化和转运到线粒体和细胞核激活WOX1。本文研究了WOX1在体内光致视网膜变性中的潜在作用。WOX1主要在围产期的内视网膜中表达，而WOX1的表达增强及其Tyr33磷酸化（p-WOX1）在成人视网膜神经节细胞中特异性地表现出来。将成熟大鼠长期暴露于恒定的低强度光（500勒克斯）下1-2个月，可导致光感受器大量死亡，并在外视网膜中存在活化的小胶质细胞、星形胶质细胞和穆勒胶质细胞。然而，内视网膜没有或几乎没有受到影响。在受损的大鼠视网膜内核层和外核层中，WOX1和p-WOX1过表达。此外，WOX1与视蛋白阳性锥体片段共定位。在患有遗传性视网膜缺陷的rd小鼠中，WOX1和p-WOX1在退化的视网膜中随着年龄的增长而上调。电镜观察发现，WOX1和p-WOX1的免疫金颗粒大量存在于退化的光感受器受损的线粒体和凝聚核中，表明WOX1在这些细胞器中被激活并易位。相比之下，在高尔基体中很少或没有发现wox1阳性颗粒。综上所述，在光致损伤和遗传性视网膜缺陷小鼠中，激活的WOX1可能导致外视网膜神经元细胞凋亡。(c) 2004 ibro。Elsevier Ltd.出版。版权所有。
WW domain-containing oxidoreductase WOX1, also named WWOX or FOR, is a known proapoptotic protein and a candidate tumor suppressor. Stress stimuli activate WOX1 via tyrosine 33 (Tyr33) phosphorylation and translocation to the mitochondria and nuclei in vitro. Here, the potential role of WOX1 in light-induced retinal degeneration in vivo was investigated. WOX1 is expressed primarily in the inner retina at perinatal stages, whereas an enhanced expression of WOX1, along with its Tyr33 phosphorylation (p-WOX1), is shown specifically in the retinal ganglion cells in adults. Prolonged exposure of mature rats to constant, low-intensity light (500 lux) for 1-2 months resulted in substantial death of photoreceptors and the presence of activated microglia, astrocytes and Muller glial in the outer retina. However, the inner retina was not or barely affected. In the damaged inner and outer nuclear layers of rat retina, WOX1 and p-WOX1 were overly expressed. Also, WOX1 colocalized with fragments of opsin-positive cones. In rd mice with an inherited retinal deficiency, upregulation of WOX1 and p-WOX1 in degenerated retina was observed with age. By electron microscopy, a large number of immunogold particles of WOX1 and p-WOX1 were found in the damaged mitochondria and condensed nuclei of degenerating photoreceptors, indicating that WOX1 undergoes activation and translocation to these organelles. In contrast, little or no WOX1-positive particles were found in the Golgi apparatus. In conclusion, activated WOX1 is likely to exert apoptosis of neuronal cells in the outer retina during the light-induced injury and in mice with an inherited retinal defect. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.