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Biochem Biophys Res Commun. 2014 Jan 10;443(2):447-52. doi: 10.1016/j.bbrc.2013.11.113. Epub 2013 Dec 6.

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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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.
Department of Interventional Radiology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, China.
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China.
Institute of Neuroscience, Soochow University, Suzhou 215123, China.
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address:
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China. Electronic address:


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.


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

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