Alpha-melanocyte stimulating hormone protects retinal pigment epithelium cells from oxidative stress through activation of melanocortin 1 receptor-Akt-mTOR signaling
| Autor: | Hui-E Bi, Lei Cheng, Jin Yao, Xiao-zhong Zhou, Qin Jiang, Zhi-qing Zhang, Li-bo Cheng |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Cell Survival Biophysics P70-S6 Kinase 1 Retinal Pigment Epithelium Biology Biochemistry Cell Line chemistry.chemical_compound Mice Internal medicine medicine Animals Humans Receptor Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Retinal pigment epithelium integumentary system Cell Biology Perifosine eye diseases alpha-Melanocyte-stimulating hormone Cell biology Oxidative Stress Endocrinology medicine.anatomical_structure chemistry alpha-MSH sense organs Reactive Oxygen Species Proto-Oncogene Proteins c-akt Receptor Melanocortin Type 1 hormones hormone substitutes and hormone antagonists Melanocortin 1 receptor Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 443(2) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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