The Amyloid Precursor Protein Plays Differential Roles in the UVA Resistance and Proliferation of Human Retinal Pigment Epithelial Cells.

Abstract

BACKGROUND:

Age-related macular degeneration (AMD) can be characterised by degeneration of retinal pigment epithelial (RPE) cells and the accumulation, in retinal drusen deposits, of amyloid beta-peptides proteolytically derived, by secretases, from the amyloid precursor protein (APP). Ultraviolet (UV) light exposure is a risk factor for the development of AMD.

OBJECTIVES:

In the current study, we investigated whether APP and/or its proteolysis are linked to the UVA resistance or proliferation of ARPE-19 human RPE cells.

METHODS:

Cell viability was determined, following UVA exposure, with prior small interfering RNA-mediated APP depletion or secretase inhibitor treatments. APP levels/proteolysis were analysed by immunoblotting. Cells were also grown in the presence/absence of secretase inhibitors to assess their effects on longer-term culture growth. Finally, the effects of APP proteolytic fragments on ARPE-19 cell proliferation were monitored following co-culture with human embryonic kidney cells stably over-expressing these fragments.

RESULTS:

Endogenous APP was depleted following UVA irradiation and β-secretase, but not α- secretase, the processing of the protein was reduced. Experimental APP depletion or γ-secretase (but not α- or β-secretase) inhibition ablated the detrimental effect of UVA on cell viability. In contrast, α-secretase, and possibly γ-secretase but not β-secretase activity, appeared to promote the longerterm proliferation of ARPE-19 cells in the absence of UVA irradiation.

CONCLUSION:

There are clear but differential links between APP expression/proteolysis and the proliferation and UVA resistance of ARPE-19 cells indicating that the protein should be investigated further in relation to the identification of possible drug targets for the treatment of AMD.

• Authors: Fatima Sultan, Edward T Parkin
• Journal: Protein and peptide letters (Protein Pept Lett) Vol. 29 Issue 4 Pg. 313-327 ( 2022) ISSN: 1875-5305 [Electronic] Netherlands
• PMID: 35176974 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Retinal Pigments
• Amyloid Precursor Protein Secretases

Topics

• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor
• Cell Proliferation
• Epithelial Cells (metabolism)
• Humans
• Retinal Pigments