| Alterations of activity and intracellular distribution of the 20S proteasome in ageing retinal pigment epithelial cells. | |
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MedLine Citation:
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PMID: 18817863 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Age-related macular degeneration (AMD) remains high incidence and accounts for a main cause of blindness in ageing people, but its mechanism is still poorly understood. Ageing and associated dysfunction of retinal pigment epithelial (RPE) cells were believed to be the pathological onset of AMD. 20S proteasome has been tightly correlated with cell ageing due to its fundamental role in maintaining cellular homeostasis, but its implication in the ageing process of human RPE cells was seldom concerned. This study aimed to demonstrate the interconnections between 20S proteasome and ageing RPE cells by characterizing age-dependent alterations of the 20S proteasome in primarily cultured human RPE cells. For this purpose, a replicative ageing RPE cell model was established and validated through testing the cell viability, beta-galactosidase activity and cellular autofluorescence. Decline in chymotrypsin-like, peptidylglutamyl-peptide hydrolase and trypsin-like activities of the 20S proteasome was detected in aged RPE cells through degradation of fluorogenic substrates. Immunofluorescence assay revealed that the 20S proteasome was concentrated in RPE nucleus, and redistributed partly to the peri-nuclear regions in old RPE passages. These age-dependent changes of the 20S complex were accompanied with a significantly increased fluorescent intensity of intracellular oxidized proteins. Further analysis of the proteasome-to-oxidized protein ratio indicated a preferred protection of the RPE nuclear proteins by the 20S proteasome, which also subsided remarkably as a function of the cell ageing. In conclusion, we demonstrated functional impairment and redistribution of the 20S proteasome with age in human RPE cells and supposed these alterations impactful on the process of RPE cell ageing and furthermore on the pathogenesis of AMD. Future researches on the mechanism of these alterations and the pathways to manipulate their effects are still strongly recommended. |
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Authors:
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Yue Li; Yu-Sheng Wang; Xue-Feng Shen; Yan-Nian Hui; Jing Han; Wei Zhao; Jie Zhu |
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Publication Detail:
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Type: Journal Article Date: 2008-09-13 |
Journal Detail:
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Title: Experimental gerontology Volume: 43 ISSN: 1873-6815 ISO Abbreviation: Exp. Gerontol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-25 Completed Date: 2009-08-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047061 Medline TA: Exp Gerontol Country: England |
Other Details:
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Languages: eng Pagination: 1114-22 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Xijing Hospital, The Fourth Military Medical University and Eye Institute of PLA, Chang-le Road 17, Xi'an, Shaanxi 710032, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged, 80 and over Cell Aging / physiology Cells, Cultured Female Humans Macular Degeneration / epidemiology, genetics, metabolism* Male Pigment Epithelium of Eye / metabolism* Proteasome Endopeptidase Complex / metabolism* |
| Chemical | |
Reg. No./Substance:
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EC 3.4.25.1/Proteasome Endopeptidase Complex |
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