title: Rapamycin sensitive mTOR activation mediates nerve growth factor (NGF) induced cell migration and pro-survival effects against hydrogen peroxide in retinal pigment epithelial cells.
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 (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.
authors.affiliation: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guo-Fan
authors.initials: GF
authors.lastname: Cao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.forename: Jerry
authors.initials: J
authors.lastname: Wan
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008268:Macular Degeneration / Q000201:enzymology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D006861:Hydrogen Peroxide; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human