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Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells

International Journal of Ophthalmology(English edition) 2018年第6期11卷 929-934页

作者： Zi Ye Shou-Zhi He Zhao-Hui Li Department of Ophthalmology the Chinese PLA General Hospital

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.

关键词： amyloid β protein retinal pigment epithelialcells proliferation apoptosis receptor for advanced glycation endproducts nuclear factor-kappaB age-related macular degeneration

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