Effect of Aß protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells.
Int J Ophthalmol
; 11(6): 929-934, 2018.
Article
in En
| MEDLINE
| ID: mdl-29977803
ABSTRACT
AIM:
To identify the effect and regulatory mechanism of amyloid ß (Aß) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aß role in the pathogenesis of age-related macular degeneration (AMD).METHODS:
The model of Aß25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aß protein on RPE cells in vitro. Based on Aß protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of Aß 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 Aß25-35 from 0.3 to 60 µmol/L, significantly reduce (P<0.01), and had the dose-dependent effect. Aß protein 60 µmol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, Aß25-35 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 phosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aß, 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 Aß protein on RPE cell apoptosis and proliferation.CONCLUSION:
Aß protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
Int J Ophthalmol
Year:
2018
Type:
Article
Affiliation country:
China