| Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cell lipofuscin. | |
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MedLine Citation:
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PMID: 16186115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nondegradable pigments that accumulate in retinal pigment epithelial (RPE) cells as lipofuscin constituents are considered to be responsible for the loss of RPE cells in recessive Stargardt disease, a blindness macular disorder of juvenile onset. This autofluorescent material may also contribute to the etiology of age-related macular degeneration. The best characterized of these fluorophores is A2E, a compound consisting of two retinoid-derived side arms extending from a pyridinium ring. Evidence indicates that photochemical mechanisms initiated by excitation from the blue region of the spectrum may contribute to the adverse effects of A2E accumulation, with the A2E photooxidation products being damaging intermediates. By studying the oxidation products (oxo-A2E) generated using oxidizing agents that add one or two oxygens at a time, together with structural analysis by heteronuclear single quantum correlation-NMR spectroscopy, we demonstrated that the oxygen-containing moieties generated within photooxidized A2E include a 5,8-monofuranoid and a cyclic 5,8-monoperoxide. We have shown that the oxidation sites can be assigned to the shorter arm of A2E, to the longer arm, or to both arms by analyzing changes in the UV-visible spectrum of A2E, and we have observed a preference for oxidation on the shorter arm. By liquid chromatography-mass spectrometry, we have also detected both monofuran-A2E and monoperoxy-A2E in aged human RPE and in eye cups of Abca4/Abcr-/- mice, a model of Stargardt disease. Because the cytotoxicity of endoperoxide moieties is well known, the production of endoperoxide-containing oxo-A2E may account, at least in part, for cellular damage ensuing from A2E photooxidation. |
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Authors:
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Young P Jang; Hiroko Matsuda; Yasuhiro Itagaki; Koji Nakanishi; Janet R Sparrow |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2005-09-26 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-28 Completed Date: 2006-02-03 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 39732-9 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Columbia University, New York, New York 10032, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics Aged Animals Cells, Cultured Chromatography, High Pressure Liquid Chromatography, Liquid Epithelial Cells / cytology* Furans / chemistry* Humans Light Lipofuscin / chemistry*, metabolism* Magnetic Resonance Spectroscopy Mass Spectrometry Mice Mice, Inbred C57BL Mice, Transgenic Middle Aged Models, Chemical Oxygen / chemistry, metabolism Peroxides / chemistry Pigment Epithelium of Eye / metabolism* Pyridinium Compounds / chemistry* Retinal Degeneration / metabolism Retinoids / chemistry* Solvents / chemistry Time Factors Ultraviolet Rays |
| Grant Support | |
ID/Acronym/Agency:
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EY 12951/EY/NEI NIH HHS; GM 34509/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/A2E compound; 0/ABCA4 protein, human; 0/ATP-Binding Cassette Transporters; 0/Abca4 protein, mouse; 0/Furans; 0/Lipofuscin; 0/Peroxides; 0/Pyridinium Compounds; 0/Retinoids; 0/Solvents; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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