Document Detail


OT-674 suppresses photooxidative processes initiated by an RPE lipofuscin fluorophore.
MedLine Citation:
PMID:  18173705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pathological processes involved in age-related macular degeneration (AMD) include retinal pigment epithelial (RPE) cell degeneration; oxidative mechanisms likely contribute to the demise of these cells. Indeed, RPE cells may be particularly susceptible to photooxidative mechanisms since they accumulate retinoid-derived photoreactive compounds that constitute the lipofuscin of the cell. Thus we undertook to test the capacity of OT-674, the reduction product (Tempol-H) of the nitroxide Tempol, to suppress photooxidative processes initiated by the RPE lipofuscin fluorophore A2E. Accordingly, when ARPE-19 cells that had accumulated A2E were irradiated at 430 nm, pretreatment with OT-674 (0.01-10 mM) was found to confer a resistance to cell death. Monitoring by quantitative HPLC also showed that OT-674 reduced A2E photooxidation in a cell-free system. Moreover, when presented with a singlet oxygen generator, OT-674 served as a quencher of singlet oxygen that was more effective than Trolox and alpha-tocopherol. We conclude that OT-674 is a potent antioxidant that suppresses photooxidative processes generated in cultured RPE cells by the lipofuscin fluorophore A2E. As oxidative damage to RPE cells is considered to be a risk factor for AMD, antioxidant therapy with OT-674 may serve a protective role.
Authors:
Jilin Zhou; Young P Jang; Stanley Chang; Janet R Sparrow
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  84     ISSN:  0031-8655     ISO Abbreviation:  Photochem. Photobiol.     Publication Date:    2008 Jan-Feb
Date Detail:
Created Date:  2008-01-04     Completed Date:  2008-03-27     Revised Date:  2011-05-05    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  75-80     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Columbia University, New York, NY, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  radiation effects
Cell Line
Cell-Free System
Color
Cyclic N-Oxides / pharmacology*
Cytoprotection / drug effects
Fluorescent Dyes / chemistry*
Humans
Hydroxylamine
Light
Lipofuscin / pharmacology*
Oxidation-Reduction / drug effects
Photochemistry
Pigment Epithelium of Eye / cytology,  drug effects*,  radiation effects*
Singlet Oxygen / metabolism
Grant Support
ID/Acronym/Agency:
EY 12951/EY/NEI NIH HHS; R01 EY012951-11/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Fluorescent Dyes; 0/Lipofuscin; 0/TEMPOL-H; 17778-80-2/Singlet Oxygen; 7803-49-8/Hydroxylamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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