Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells
Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells作者机构：Department of Ophthalmology the Chinese PLA General Hospital
出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)
年 卷 期：2018年第11卷第6期
页 面：929-934页
核心收录：
学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学]
主 题：amyloid β protein retinal pigment epithelialcells proliferation apoptosis receptor for advanced glycation endproducts nuclear factor-kappaB age-related macular degeneration
摘 要：AIM： To identify the effect and regulatory mechanism of amyloid β （Aβ） protein on retinal pigment epithelial （RPE） cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-related macular degeneration （AMD）. METHODS： The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells in vitro. Based on Aβ protein, the specific inhibitors （HY-50682 or BAY11-7082） or activating agent （lipopolysaccharide） was used to analyze the regulatory mechanism of Aβ protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS： The number of RPE cells, treated with Aβ25-35 from 0.3 to 60 μmol/L, significantly reduce （P〈0.01）, and had the dose-dependent effect. Aβ protein 60 μmol/L inhibits the G1/S phase transition （P〈0.01） and down-regulated cyclin E mRNA level （P〈0.01）. Similarly, Aβ25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB （NF-κB） activity and hosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aβ, the cell numbers, NF-κB activity, phosphorylated Iκ-Ba level, receptor for advanced glycation endproducts （RAGE） gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-κB signaling pathway involved in the regulation of Aβ protein on RPE cell apoptosis and proliferation. CONCLUSION： Aβ protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.
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