title: Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling.
abstract: Patients with age related macular degeneration (AMD) will develop vision loss in the center of the visual field. Reactive oxygen species (ROS)-mediated retinal pigment epithelium (RPE) cell apoptosis is an important contributor of AMD. In this study, we explored the pro-survival effect of α-melanocyte stimulating hormone (α-MSH) on oxidative stressed RPE cells. We found that α-MSH receptor melanocortin 1 receptor (MC1R) was functionally expressed in primary and transformed RPE cells. RPE cells were response to α-MSH stimulation. α-MSH activated Akt/mammalian target of rapamycin (mTOR) and Erk1/2 signalings in RPE cells, which were inhibited by MC1R siRNA knockdown. α-MSH protected RPE cells from hydrogen peroxide (H₂O₂)-induced apoptosis, an effect that was almost abolished when MC1R was depleted by siRNA. α-MSH-mediated S6K1 activation and pro-survival effect against H₂O₂ was inhibited by Akt inhibitors (perifosine, MK-2206 and LY294002). Further, mTOR inhibition by rapamycin, or by mTOR siRNA knockdown, diminished α-MSH's pro-survival effect in RPE cells. Thus, Akt and its downstream mTOR signaling mediates α-MSH-induced survival in RPE cells. In summary, we have identified a new α-MSH-MC1R physiologic pathway that reduces H₂O₂-induced RPE cell damage, and might minimize the risk of developing AMD.
authors: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China; Eye Department, Li-yang City Hospital of Traditional Chinese Medicine, Li-yang City 213300, China.
authors: Li-bo
authors: LB
authors: Cheng
authors: Department of Interventional Radiology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, China.
authors: Lei
authors: L
authors: Cheng
authors: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China.
authors: Hui-e
authors: HE
authors: Bi
authors: Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors: Zhi-qing
authors: ZQ
authors: Zhang
authors: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China.
authors: Jin
authors: J
authors: Yao
authors: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address: zhouxz@suda.edu.cn.
authors: Xiao-zhong
authors: XZ
authors: Zhou
authors: The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China. Electronic address: dryaojin@yahoo.com.
authors: Qin
authors: Q
authors: Jiang
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH; D051057:Proto-Oncogene Proteins c-akt
keywords: AMD; Age related macular degeneration (AMD); Apoptosis and Akt/mTOR signaling; H(2)O(2); MC1R; Melanocortin 1 receptor (MC1R); RPE; Retinal pigment epithelium (RPE); age-related macular degeneration; hydrogen peroxide; mTOR; mammalian target of rapamycin; melanocortin 1 receptor; retinal pigment epithelium; α-MSH; α-Melanocyte stimulating hormone (α-MSH); α-melanocyte stimulating hormone