机构：[a]The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China[b]Eye Department, Li-yang City Hospital of Traditional Chinese Medicine, Li-yang City 213300, China[c]Department of Interventional Radiology, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, China[d]Institute of Neuroscience, Soochow University, Suzhou 215123, China[e]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
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 alpha-melanocyte stimulating hormone (alpha-MSH) on oxidative stressed RPE cells. We found that alpha-MSH receptor melanocortin I receptor (MC1R) was functionally expressed in primary and transformed RPE cells. RPE cells were response to alpha-MSH stimulation. alpha-MSH activated Akt/mammalian target of rapamycin (mTOR) and Erk1/2 signalings in RPE cells, which were inhibited by MC1R siRNA knockdown. alpha-MSH protected RPE cells from hydrogen peroxide (H2O2)-induced apoptosis, an effect that was almost abolished when MC1R was depleted by siRNA. alpha-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 alpha-MSH's pro-survival effect in RPE cells. Thus, Akt and its downstream mTOR signaling mediates alpha-MSH-induced survival in RPE cells. In summary, we have identified a new alpha-MSH-MC1R physiologic pathway that reduces H2O2-induced RPE cell damage, and might minimize the risk of developing AMD. (C) 2013 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of China [81070744, 81271028]; post-doc fund of Jiangsu Province [1002009B]; Medical Science and Technology Development Project Fund of Nanjing [ZKX12047, YKK12208, YKK12207]
第一作者机构：[a]The Affiliated Eye Hospital, Nanjing Medical University, Nanjing City 210029, China[b]Eye Department, Li-yang City Hospital of Traditional Chinese Medicine, Li-yang City 213300, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Orthopedics, The Second Affiliated Hospital of Soochow University, San-xiang Road, Suzhou 215000, China.[*2]The Affiliated Eye Hospital, Nanjing Medical University, 138 Han-zhong Road, Nanjing City 210029, China.
推荐引用方式(GB/T 7714)：
Li-bo Cheng,Lei Cheng,Hui-e Bi,et al.Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2014,443(2):447-52.doi:10.1016/j.bbrc.2013.11.113.
APA：
Li-bo Cheng,Lei Cheng,Hui-e Bi,Zhi-qing Zhang,Jin Yao...&Qin Jiang.(2014).Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,443,(2)
MLA：
Li-bo Cheng,et al."Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 443..2(2014):447-52
