学科主题 | 临床医学 |
Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration | |
Zhang, J.1,2,3; Bai, Y.1,2,3; Huang, L.1,2,3; Qi, Y.1,2,3; Zhang, Q.1,2,3; Li, S.1,2,3; Wu, Y.4; Li, X.1,2,3 | |
刊名 | CELL DEATH & DISEASE
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2015-11-01 | |
DOI | 10.1038/cddis.2015.330 |
卷 | 6 |
收录类别 | SCI |
文章类型 | Article |
WOS标题词 | Science & Technology |
类目[WOS] | Cell Biology |
资助者 | Beijing Nova Program ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Beijing Nova Program ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China |
研究领域[WOS] | Cell Biology |
关键词[WOS] | RAPAMYCIN ; DISEASE ; HEALTH ; RPE ; BISRETINOIDS ; PATHOGENESIS ; INHIBITION ; ACTIVATION ; MECHANISMS ; PRODUCTS |
英文摘要 | Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. Degeneration of retinal pigment epithelial (RPE) cells is a crucial causative factor responsible for the onset and progression of AMD. A2E, a major component of toxic lipofuscin implicated in AMD, is deposited in RPE cells with age. However, the mechanism whereby A2E may contribute to the pathogenesis of AMD remains unclear. We demonstrated that A2E was a danger signal of RPE cells, which induced autophagy and decreased cell viability in a concentration-and time-dependent manner. Within 15 min after the treatment of RPE with 25 mu M A2E, the induction of autophagosome was detected by transmission electron microscopy. After continuous incubating RPE cells with A2E, intense punctate staining of LC3 and increased expression of LC3-II and Beclin-1 were identified. Meanwhile, the levels of intercellular adhesion molecule (ICAM), interleukin (IL) 1 beta, IL2, IL-6, IL-8, IL-17A, IL-22, macrophage cationic peptide (MCP)-1, stromal cell-derived factor (SDF)-1, and vascular endothelial growth factor A (VEGFA) were elevated. The autophagic inhibitor 3-methyladenine (3-MA) and activator rapamycin were also used to verify the effect of autophagy on RPE cells against A2E. Our results revealed that 3-MA decreased the autophagosomes and LC3 puncta induced by A2E, increased inflammation-associated protein expression including ICAM, IL1 beta, IL2, IL-6, IL-8, IL-17A, IL-22, and SDF-1, and upregulated VEGFA expression. Whereas rapamycin augmented the A2E-mediated autophagy, attenuated protein expression of inflammation-associated and angiogenic factors, and blocked the Akt/mTOR pathway. Taken together, A2E induces autophagy in RPE cells at the early stage of incubation, and this autophagic response can be inhibited by 3-MA or augmented by rapamycin via the mTOR pathway. The enhancement of autophagy has a protective role in RPE cells against the adverse effects of A2E by reducing the secretion of inflammatory cytokines and VEGFA. |
语种 | 英语 |
所属项目编号 | Z131102000413004 ; 2015M570901 ; 2011CB510200 ; 81470649 ; 81271018 |
资助者 | Beijing Nova Program ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; Beijing Nova Program ; China Postdoctoral Science Foundation ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China |
WOS记录号 | WOS:000367155300011 |
Citation statistics | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.bjmu.edu.cn/handle/400002259/51306 |
Collection | 北京大学第二临床医学院_眼科 |
作者单位 | 1.Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China 2.Minist Educ, Key Lab Vis Loss & Restorat, Beijing 100044, Peoples R China 3.Beijing Key Lab Diag & Treatment Retinal & Choroi, Beijing 100044, Peoples R China 4.Xiamen Univ, Eye Inst, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen 361102, Fujian Provine, Peoples R China |
Recommended Citation GB/T 7714 | Zhang, J.,Bai, Y.,Huang, L.,et al. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration[J]. CELL DEATH & DISEASE,2015,6. |
APA | Zhang, J..,Bai, Y..,Huang, L..,Qi, Y..,Zhang, Q..,...&Li, X..(2015).Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration.CELL DEATH & DISEASE,6. |
MLA | Zhang, J.,et al."Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration".CELL DEATH & DISEASE 6(2015). |
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