Our previous work reported that minocycline induced inhibition of microglial activation aggravated visual injury in an oxygen induced retinopathy animal model. We hypothesized that minocycline might have aggravated injury to the photoreceptor. Some patients who use minocycline to treat acne complain of visual impairment; however, no studies have addressed minocycline toxicity to photoreceptors. Here, we identified mechanistic effect of minocycline on photoreceptor apoptosis. The results of Cell Counting Kit-8 and Ki67 staining demonstrated that minocycline inhibited the proliferation of 661W cells, and flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) demonstrated that minocycline promoted cell apoptosis. Additionally, minocycline administration activated signaling associated with endoplasmic reticulum stress, the pancreatic ER kinase-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-CCAAT/enhancer-binding protein homologous protein (CHOP) cascade, which represented the key mechanism underlying the initiation of apoptosis. Moreover, we observed downregulated nuclear factor erythroid 2-related factor 2 (Nrf2) after administration of minocycline for 12 h (12 hours) and Nrf2 transferred from nuclear to cytoplasm after 6 h, indicating that Nrf2 in nuclear may alleviated the pro-apoptotic effect of minocycline on photoreceptor cells. Upregulating Nrf2 inhibited apoptosis in minocycline treated 661W cells. These represent the first data demonstrating minocycline toxicity to photoreceptors via its pro-apoptotic effects through the regulation of ER stress pathways.

中文翻译：

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Minocycline通过调节ER应激诱导光感受器细胞凋亡。

我们以前的工作报告说，在氧引起的视网膜病变动物模型中，米诺环素诱导的对小胶质细胞活化的抑制作用加剧了视觉损伤。我们假设米诺环素可能会加剧感光器的损伤。一些使用米诺环素治疗痤疮的患者抱怨视力障碍。然而，没有研究涉及米诺环素对感光体的毒性。在这里，我们确定了米诺环素对感光细胞凋亡的机制作用。Cell Counting Kit-8和Ki67染色的结果表明，米诺环素抑制661W细胞的增殖，流式细胞仪和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）表明，米诺环素可促进细胞凋亡。此外，米诺环素给药可激活与内质网应激相关的信号，胰腺ER激酶样ER激酶（PERK）-真核翻译起始因子2α（eIF2α）-CCAAT /增强子结合蛋白同源蛋白（CHOP）级联反应，代表了细胞凋亡起始的关键机制。此外，我们观察到米诺环素给药12小时（12小时）后核因子红系2相关因子2（Nrf2）下调，并且6小时后Nrf2从核转移到细胞质，表明核内Nrf2可能减轻了促凋亡作用。诺霉素对感光细胞的影响。Nrf2上调抑制了米诺环素处理的661W细胞的凋亡。这些代表了第一个数据，表明米诺环素通过调节ER应激途径的促凋亡作用而对光感受器产生毒性。