Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E
| العنوان: | Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E |
|---|---|
| المؤلفون: | Eiichi Okada, Yusuke Murakami, Tsutomu Yasukawa, Yasuhiro Ikeda, Yasuo Yanagi, Khandakar A.S.M. Saadat, Yoko Nomura, Xue Tan |
| المصدر: | FEBS Open Bio, Vol 4, Iss C, Pp 1007-1014 (2014) FEBS Open Bio |
| بيانات النشر: | Wiley, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Programmed cell death, STGD, Stargardt disease, SOD1, SOD2, Mitochondrion, Biology, RPE, retinal pigment epithelial cells, Article, General Biochemistry, Genetics and Molecular Biology, Lipofuscin, Autophagy, medicine, SEM, scanning electron microscopy, AMD, age-related macular degeneration, TEM, transmission electron microscopy, Retinal pigment epithelium, lcsh:QH301-705.5, chemistry.chemical_classification, Reactive oxygen species, mROS, mitochondrial reactive oxygen species, eye diseases, Mitochondria, Cell biology, medicine.anatomical_structure, lcsh:Biology (General), chemistry, sense organs, 3MA, 3-methyladenine |
| الوصف: | Highlights • Autophagy was augmented in RPE cells in the presence of a lipofuscin pigment, A2E. • RPE cell death was induced in the presence of A2E with an autophagy inhibitor. • Inhibition of autophagy resulted in the accumulation of abnormal mitochondria. • Autophagy in RPE cells prevents the accumulation of damaged cellular molecules. 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. |
| تدمد: | 2211-5463 |
| DOI: | 10.1016/j.fob.2014.11.003 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d5b65dabb701ddfa6e98a83b3adcc15 https://doi.org/10.1016/j.fob.2014.11.003 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d5b65dabb701ddfa6e98a83b3adcc15 |
| قاعدة البيانات: | OpenAIRE |
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