| Enzymatic Degradation of A2E, a Retinal Pigment Epithelial Lipofuscin Bisretinoid. | |
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MedLine Citation:
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PMID: 21166406 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Some forms of blinding macular disease are associated with excessive accumulation of bisretinoid lipofuscin in retinal pigment epithelial (RPE) cells of the eye. This material is refractory to lysosomal enzyme degradation. In addition to gene and drug-based therapies, treatments that reverse the accumulation of bisretinoid would be beneficial. Thus, we have examined the feasibility of degrading the bisretinoids by delivery of exogenous enzyme. As proof of principle we report that horseradish peroxidase (HRP) can cleave the RPE bisretinoid A2E. In both cell-free and cell-based assays, A2E levels were decreased in the presence of HRP. HRP-associated cleavage products were detected by ultraperformance liquid chromatography (UPLC) coupled to electrospray ionization mass spectrometry, and the structures of the aldehyde-bearing cleavage products were elucidated by (18)O-labeling and (1)H NMR spectroscopy and by recording UV-vis absorbance spectra. These findings indicate that RPE bisretinoids such as A2E can be degraded by appropriate enzyme activities. |
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Authors:
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Yalin Wu; Jilin Zhou; Nathan Fishkin; Bruce E Rittmann; Janet R Sparrow |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-12-17 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: - ISSN: 1520-5126 ISO Abbreviation: - Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Ophthalmology and ‡ Department of Pathology and Cell Biology, Columbia University , 630 West 168th Street, New York, New York 10032, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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