Document Detail


Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage.
MedLine Citation:
PMID:  22773902     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage.
METHODS: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H(2)O(2). Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 μM), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor-dependent effects. All tests were performed in triplicate.
RESULTS: H(2)O(2) at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose-dependent protective effects on RPE cells against H(2)O(2). Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H(2)O(2) alone (all p<0.05). Using cells cultured without H(2)O(2) as the control, cell viability of cells treated with H(2)O(2) after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H(2)O(2). Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M).
CONCLUSIONS: Melatonin has a partial protective effect on RPE cells against H(2)O(2) damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M).
Authors:
Richard B Rosen; Dan-Ning Hu; Min Chen; Steven A McCormick; Joseph Walsh; Joan E Roberts
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-20
Journal Detail:
Title:  Molecular vision     Volume:  18     ISSN:  1090-0535     ISO Abbreviation:  Mol. Vis.     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-09     Completed Date:  2012-11-13     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9605351     Medline TA:  Mol Vis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1640-8     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, New York Eye and Ear Infirmary, New York Medical College, New York, NY, USA.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology*
Apoptosis / drug effects
Cell Line
Cell Survival / drug effects
Dose-Response Relationship, Drug
Epithelial Cells / cytology,  drug effects*,  metabolism
Humans
Hydrogen Peroxide / pharmacology
Male
Melatonin / pharmacology*
Middle Aged
Oxidative Stress / drug effects
Primary Cell Culture
Receptors, Melatonin / antagonists & inhibitors*,  metabolism
Retinal Pigment Epithelium / cytology,  drug effects*,  metabolism
Tetrazolium Salts
Thiazoles
Tryptamines / pharmacology
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Receptors, Melatonin; 0/Tetrazolium Salts; 0/Thiazoles; 0/Tryptamines; 117946-91-5/luzindole; 298-93-1/thiazolyl blue; 73-31-4/Melatonin; 7722-84-1/Hydrogen Peroxide
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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