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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Authors: | Cao Guo-Fan Liu Yuan Yang Wen Wan Jerry Yao Jin Wan Yinsheng Jiang Qin |
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Institution: | aThe Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China;bDepartment of Biology, Providence College, Providence, RI 02918, United States |
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Abstract: | 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 (H2O2)-induced cell apoptosis. NGF also induces RPE cell migration, the latter is important for retinal regeneration and the recovery from AMD. H2O2 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 H2O2 treated RPE cells. |
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Keywords: | Abbreviations: AMD age-related macular degeneration NGF nerve growth factor RPE retinal pigment epithelium H2O2 hydrogen peroxide mTOR mammalian target of rapamycin AMPK AMP activated protein kinase MAPK mitogen-activated protein kinase PARP poly ADP ribose polymerase |
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