Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.fob.2014.11.003
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 lipofuscin pigment A2E manganese superoxide dismutase messenger RNA mitochondrial transcription factor A parkin peroxisome proliferator activated receptor gamma coactivator 1alpha peroxisome proliferator activated receptor gamma coactivator 1beta reactive oxygen metabolite transcription factor Nrf1 unclassified drug Article autophagosome autophagy cell damage cell death cell survival cell vacuole cell viability controlled study cytotoxicity gene expression human human cell culture mitochondrion pigment cell real time polymerase chain reaction spheroid cell transmission electron microscopy upregulation |
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. https://doi.org/10.1016/j.fob.2014.11.003 | 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 | URI: | https://scholarbank.nus.edu.sg/handle/10635/183646 | ISSN: | 22115463 | DOI: | 10.1016/j.fob.2014.11.003 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1016_j_fob_2014_11_003.pdf | 1.87 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License