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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.

Author information

1
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.
2
Department of Interventional Radiology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, China.
3
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China.
4
Institute of Neuroscience, Soochow University, Suzhou 215123, China.
5
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China. Electronic address: zhouxz@suda.edu.cn.
6
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China. Electronic address: dryaojin@yahoo.com.

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.

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

PMID:
24316214
DOI:
10.1016/j.bbrc.2013.11.113
[Indexed for MEDLINE]

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