Dataset Information
Effect of A? protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells.
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ABSTRACT: Aim
To identify the effect and regulatory mechanism of amyloid ? (A?) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify A? role in the pathogenesis of age-related macular degeneration (AMD).Methods
The model of A?25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of A? protein on RPE cells in vitro. Based on A? protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of A? 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 A?25-35 from 0.3 to 60 µmol/L, significantly reduce (P<0.01), and had the dose-dependent effect. A? protein 60 µmol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, A?25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-?B) activity and phosphorylated I?-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the A?, the cell numbers, NF-?B activity, phosphorylated I?-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-?B signaling pathway involved in the regulation of A? protein on RPE cell apoptosis and proliferation.Conclusion
A? protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-?B signaling pathway in RPE cell.
SUBMITTER: Ye Z
PROVIDER: S-EPMC6010384 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells.
International journal of ophthalmology 20180618 6
<h4>Aim</h4>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).<h4>Methods</h4>The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells <i>in vitro</i>. Based on Aβ protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating ...[more]