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Enzymatic degradation of A2E, a retinal pigment epithelial lipofuscin bisretinoid.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2011 Feb 02; Vol. 133 (4), pp. 849-57. - Publication Year :
- 2011
-
Abstract
- 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 18O-labeling and 1H 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.
- Subjects :
- Adult
Aldehydes chemistry
Cell Line
Cell Survival drug effects
Cell-Free System
Chromatography, High Pressure Liquid
Humans
Intracellular Space metabolism
Lipofuscin chemistry
Lipofuscin toxicity
Magnetic Resonance Spectroscopy
Mass Spectrometry
Pyridinium Compounds chemistry
Pyridinium Compounds toxicity
Retinal Pigment Epithelium cytology
Retinal Pigment Epithelium drug effects
Retinoids chemistry
Retinoids toxicity
Horseradish Peroxidase metabolism
Lipofuscin metabolism
Pyridinium Compounds metabolism
Retinal Pigment Epithelium metabolism
Retinoids metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 133
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 21166406
- Full Text :
- https://doi.org/10.1021/ja107195u