| First Author | Cheng LB | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 443 |
| Issue | 2 | Pages | 447-52 |
| PubMed ID | 24316214 | Mgi Jnum | J:211872 |
| Mgi Id | MGI:5576829 | Doi | 10.1016/j.bbrc.2013.11.113 |
| Citation | Cheng LB, et al. (2014) Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling. Biochem Biophys Res Commun 443(2):447-52 |
| abstractText | 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 1 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 (H(2)O(2))-induced apoptosis, an effect that was almost abolished when MC1R was depleted by siRNA. alpha-MSH-mediated S6K1 activation and pro-survival effect against H(2)O(2) 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 H(2)O(2)-induced RPE cell damage, and might minimize the risk of developing AMD. |
