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Title: Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E
Authors: Saadat, K.A.S.M
Murakami, Y
Tan, X
Nomura, Y
Yasukawa, T
Okada, E
Ikeda, Y
Yanagi, Y 
Keywords: 3 methyladenine
adenosine triphosphate
copper zinc superoxide dismutase
lipofuscin pigment A2E
manganese superoxide dismutase
messenger RNA
mitochondrial transcription factor A
peroxisome proliferator activated receptor gamma coactivator 1alpha
peroxisome proliferator activated receptor gamma coactivator 1beta
reactive oxygen metabolite
transcription factor Nrf1
unclassified drug
cell damage
cell death
cell survival
cell vacuole
cell viability
controlled study
gene expression
human cell culture
pigment cell
real time polymerase chain reaction
spheroid cell
transmission electron microscopy
Issue Date: 2014
Citation: Saadat, K.A.S.M, Murakami, Y, Tan, X, Nomura, Y, Yasukawa, T, Okada, E, Ikeda, Y, Yanagi, Y (2014). Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E. FEBS Open Bio 4 : 1007-1014. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: In this study, we show augmented autophagy in the retinal pigment epithelial cell line ARPE-19 when cultured in the presence of the lipofuscin pigment A2E. A2E alone does not induce RPE cell death, but cell death was induced in the presence of A2E with the autophagy inhibitor 3-methyladenine (3MA), with a concomitant increase in the generation of mitochondrial reactive oxygen species. On the other hand, the ATP production capacity of mitochondria was decreased in the presence of A2E, and pharmacological inhibition of autophagy had no additional effects. The altered mRNA expression level of mitochondrial function markers was confirmed by real-time polymerase chain reaction, which showed that the antioxidant enzymes SOD1 and SOD2 were not reduced in the presence of A2E alone, but significantly suppressed with the addition of 3MA. Furthermore, transmission electron micrography revealed autophagic vacuole formation in the presence of A2E, and inhibition of autophagy resulted in the accumulation of abnormal mitochondria with loss of cristae. Spheroid culture of human RPE cells demonstrated debris accumulation in the presence of A2E, and this accumulation was accelerated in the presence of 3MA. These results indicate that autophagy in RPE cells is a vital cytoprotective process that prevents the accumulation of damaged cellular molecules. © 2014 The Authors.
Source Title: FEBS Open Bio
ISSN: 22115463
DOI: 10.1016/j.fob.2014.11.003
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

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