Accumulation of oxidized lipid-protein complexes alters phagosome maturation in retinal pigment epithelium

Cellular and Molecular Life Sciences : CMLS
George HoppeJonathan Sears

Abstract

Lipid peroxidation has been implicated in many age-associated disorders including macular degeneration of the retina. We sought to elucidate the mechanism by which accumulation of oxidized LDL (oxLDL) reduces the ability of retinal pigment epithelium (RPE) to process photoreceptor outer segments (OS) as a model of peroxidation-induced disruption of phagocytosis. OxLDL did not reduce the lysosomal hydrolytic capacity of the RPE, but efficiently inhibited processing of various internalized proteins. OxLDL caused a delay in the acquisition of late lysosomal markers by newly formed phagosomes. At the same time, an excessive accumulation of markers of early phagosomal compartments was also observed. The activity of phosphatidylinositol 3-kinase (PI3K) was reduced in phagosomes of the RPE treated with oxLDL. These results suggest that accumulation of oxidized lipid-protein complexes in the RPE impedes phagosome maturation by blocking PI3K recruitment to the phagosomal membrane, leading to delayed processing of internalized OS.

Citations

Apr 25, 2013·Visual Neuroscience·Laura S FrostKathleen Boesze-Battaglia
Feb 26, 2009·The Journal of Biological Chemistry·Monika Damek-PoprawaKathleen Boesze-Battaglia
Feb 6, 2010·Physiology·Brian M Kevany, Krzysztof Palczewski
Sep 8, 2015·Progress in Retinal and Eye Research·Deborah A FerringtonKai Kaarniranta
Aug 22, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sonia GuhaClaire H Mitchell
Jan 29, 2021·International Journal of Molecular Sciences·Arunbalaji PugazhendhiBalamurali Ambati
Feb 28, 2020·Progress in Retinal and Eye Research·Aparna LakkarajuDavid S Williams
Oct 22, 2020·Journal of Lipid Research·Sriganesh Ramachandra Rao, Steven J Fliesler
Mar 5, 2021·Journal of Lipid Research·Sriganesh Ramachandra Rao, Steven J Fliesler
Oct 8, 2020·Molecular Aspects of Medicine·Ji NieXiawei Wei

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