Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor–Akt–mTOR signaling |
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Authors: | Li-bo Cheng Lei Cheng Hui-e Bi Zhi-qing Zhang Jin Yao Xiao-zhong Zhou Qin Jiang |
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Institution: | 1. The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China;2. Eye Department, Li-yang City Hospital of Traditional Chinese Medicine, Li-yang City 213300, China;3. Department of Interventional Radiology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, China;4. Institute of Neuroscience, Soochow University, Suzhou 215123, China;5. Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China |
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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. |
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Keywords: | AMD age-related macular degeneration RPE retinal pigment epithelium α-MSH α-melanocyte stimulating hormone mTOR mammalian target of rapamycin MC1R melanocortin 1 receptor H2O2 hydrogen peroxide |
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