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  • Sultan and Parkin 2022

    Rights statement: The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/10.2174/0929866529666220217124152

    Accepted author manuscript, 1.59 MB, PDF document

    Embargo ends: 17/02/23

    Available under license: CC BY-NC: Creative Commons Attribution-NonCommercial 4.0 International License

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

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
<mark>Journal publication date</mark>30/03/2022
<mark>Journal</mark>Protein and Peptide Letters
Issue number4
Volume29
Number of pages15
Pages (from-to)313-327
Publication StatusPublished
Early online date17/02/22
<mark>Original language</mark>English

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 -secretase, processing of the protein was reduced. Experimental APP depletion or -secretase (but not - or β-secretase) inhibition ablated the detrimental effect of UVA on cell viability. In contrast, -secretase, and possibly -secretase but not β-secretase activity, appeared to promote the longer-term proliferation of ARPE-19 cells in the absence of UVA irradiation Conclusions: 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.

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The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/10.2174/0929866529666220217124152