| Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity. | |
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MedLine Citation:
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PMID: 21345980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To evaluate the potential role that FoxO transcription factors play in modulating resveratrol's protective effects against oxidative stress in lens epithelial cells. METHODS: Primary human or porcine lens epithelial cells (LECs) were treated with resveratrol (RES) 25 μM and incubated under either physiologic (5%) or chronic hyperoxic (40%) oxygen conditions. Acute oxidative stress was applied using 600 μM H(2)O(2). Changes in expression of FoxO1A, FoxO3A, and FoxO4 were analyzed. The production of intracellular reactive oxygen species (iROS), SA-β-galactosidase (SA-β-gal) activity, and autofluorescence (AF) was assessed by flow cytometry. SiRNAs of FoxO1A, FoxO3A, and FoxO4 were used to study the roles that these transcription factors play in resveratrol's protective effects against cell death induced by oxidative stress. RESULTS: RES incubation under 40% oxygen increased the expression of FoxO1A, FoxO3A, and FoxO4. RES also increases mitochondrial membrane potential under 5% and/or 40% O(2) conditions and significantly decreased iROS, SA-β-gal, and AF normally induced by hyperoxic conditions. While RES had a mild pro-apoptotic effect in nonstressed cells, it significantly prevented apoptosis induced by H(2)O(2) stress. SiRNA inhibition of FoxO1A, FoxO3A, and FoxO4 not only led to loss of the anti-apoptotic effects of RES in stressed cells but actually exhibited a mild pro-apoptotic effect. CONCLUSIONS: RES exerts a protective effect against oxidative damage in LEC cultures. The levels of expression of FoxO1A, FoxO3A, and FoxO4 appear to play a central role in determining the pro- or anti-apoptotic effects of RES. This has implications for future studies on oxidative stress-related lenticular disorders such as cataract formation. |
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Authors:
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Guorong Li; Coralia Luna; Iris D Navarro; David L Epstein; Wei Huang; Pedro Gonzalez; Pratap Challa |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-21 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-22 Completed Date: 2011-09-01 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 4395-401 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Duke Eye Center, Duke University Medical Center, Durham, North Carolina 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors Animals Antioxidants / pharmacology Apoptosis / drug effects Blotting, Western Cataract / metabolism, pathology, prevention & control* Cells, Cultured Disease Models, Animal Epithelial Cells / drug effects*, metabolism, pathology Flow Cytometry Forkhead Transcription Factors / genetics, metabolism* Gene Expression Regulation / drug effects Humans Lens, Crystalline / drug effects, metabolism*, pathology Membrane Potential, Mitochondrial Oxidative Stress / drug effects*, physiology Polymerase Chain Reaction RNA / genetics Stilbenes / pharmacology* Swine |
| Grant Support | |
ID/Acronym/Agency:
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EY016228/EY/NEI NIH HHS; EY01894/EY/NEI NIH HHS; EY05722/EY/NEI NIH HHS; K23 EY014019/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Antioxidants; 0/Forkhead Transcription Factors; 0/Stilbenes; 501-36-0/resveratrol; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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