The involvement of ATF4 and S-opsin in retinal photoreceptor cell damage induced by blue LED light
The involvement of ATF4 and S-opsin in retinal photoreceptor cell damage induced by blue LED light
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发表时间：
2017-03
期刊：
影响因子：
2.2
通讯作者：
E. Ooe;K. Tsuruma;Yoshiki Kuse;Saori Kobayashi;M. Shimazawa;H. Hara
中科院分区：
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作者：
E. Ooe;K. Tsuruma;Yoshiki Kuse;Saori Kobayashi;M. Shimazawa;H. Hara
用途蓝光是可见光谱中波长较短的高能量发射光。蓝光诱导感光细胞凋亡，并导致年龄相关性黄斑变性或视网膜色素变性。在本研究中，我们研究了内质网（ER）应激的蓝光发光二极管（LED）曝光在小鼠感光细胞诱导的作用。方法将小鼠视网膜光感受器细胞株培养后，置于蓝光LED（464 nm蓝光LED，450 lx，3 ~ 24 h）照射下，观察细胞形态学变化。使用定量实时逆转录（RT）-PCR和免疫印迹分析检测未折叠蛋白反应途径中涉及的因子的表达。用免疫组化染色法观察了短波长视蛋白（S-opsin）在小鼠感光细胞中的聚集。还研究了S-视蛋白敲低对鼠感光细胞系中ATF 4表达的影响。结果蓝光照射后，bip、atf 4和grp 94 mRNA表达增加，ATF 4蛋白表达增加，泛素化蛋白表达增加。暴露于蓝色LED光与ER应激诱导剂（衣霉素和二硫苏糖醇）的组合诱导S-视蛋白的聚集。S-视蛋白mRNA敲低阻止了响应于暴露于蓝色LED光的ATF 4表达的诱导。结论蓝光照射诱导的S-视蛋白聚集可引起内质网应激，尤其是ATF 4的激活。
Purpose Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells. Methods The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h). The expression of the factors involved in the unfolded protein response pathway was examined using quantitative real-time reverse transcription (RT)-PCR and immunoblot analysis. The aggregation of short-wavelength opsin (S-opsin) in the murine photoreceptor cells was observed with immunostaining. The effect of S-opsin knockdown on ATF4 expression in the murine photoreceptor cell line was also investigated. Results Exposure to blue LED light increased the bip, atf4, and grp94 mRNA levels, induced the expression of ATF4 protein, and increased the levels of ubiquitinated proteins. Exposure to blue LED light in combination with ER stress inducers (tunicamycin and dithiothreitol) induced the aggregation of S-opsin. S-opsin mRNA knockdown prevented the induction of ATF4 expression in response to exposure to blue LED light. Conclusions These findings indicate that the aggregation of S-opsin induced by exposure to blue LED light causes ER stress, and ATF4 activation in particular.