Rapamycin sensitive mTOR activation mediates nerve growth factor (NGF) induced cell migration and pro-survival effects against hydrogen peroxide in retinal pigment epithelial cells
Rapamycin sensitive mTOR activation mediates nerve growth factor (NGF) induced cell migration and pro-survival effects against hydrogen peroxide in retinal pigment epithelial cells
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DOI：
10.1016/j.bbrc.2011.09.094
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发表时间：
2011-10-28
影响因子：
3.1
通讯作者：
Jiang, Qin
中科院分区：
文献类型：
--
作者：
Cao, Guo-Fan;Liu, Yuan;Jiang, Qin
年龄相关性黄斑变性 (AMD) 患者的视野中心视力丧失。氧化应激在这一进展中发挥着重要作用。神经生长因子 (NGF) 对于交感神经元和感觉神经元的存活和维持非常重要，NGF 滴眼剂可改善 AMD 患者的视力和电功能活动。然而，其中涉及的分子机制和信号事件尚未得到充分研究。使用培养的人视网膜色素上皮 (RPE) 细胞，我们在此证明 NGF 可以保护 RPE 细胞免受过氧化氢 (H(2)O(2)) 诱导的细胞凋亡。 NGF 还诱导 RPE 细胞迁移，后者对于视网膜再生和 AMD 的恢复非常重要。 H(2)O(2) 降低S6 磷酸化和细胞活力，而NGF 可恢复这一作用。雷帕霉素是哺乳动物雷帕霉素靶点 (mTOR) 的药理学抑制剂，可减少 NGF 诱导的 S6 磷酸化、细胞迁移和针对氧化应激的保护作用。总的来说，我们得出结论，雷帕霉素敏感的 mTOR 信号传导的激活介导 NGF 诱导的 H(2)O(2) 处理的 RPE 细胞中的细胞迁移和促生存作用。 (C) 2011 Elsevier Inc. 保留所有权利。
Patients with age related macular degeneration (AMD) have a loss of vision in the center of the visual field. Oxidative stress plays an important role in this progress. Nerve growth factor (NGF) is important for the survival and maintenance of sympathetic and sensory neurons and NGF eye drops improve visual acuity and electro-functional activity in patients with AMD. However, the molecular mechanisms and signaling events involved in this have not been fully investigated. Using cultured human retinal pigment epithelial (RPE) cells, we demonstrate here that NGF protects RPE cells against hydrogen peroxide (H(2)O(2))-induced cell apoptosis. NGF also induces RPE cell migration, the latter is important for retinal regeneration and the recovery from AMD. H(2)O(2) decreases S6 phosphorylation and cell viability, which is restored by NGF. Rapamycin, the pharmacologic inhibitor of mammalian target of rapamycin (mTOR), diminished NGF-induced S6 phosphorylation, cell migration and protective effects against oxidative stress. Collectively, we conclude that activation of rapamycin sensitive mTOR signaling mediates NGF induced cell migration and pro-survival effects in H(2)O(2) treated RPE cells. (C) 2011 Elsevier Inc. All rights reserved.