Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells
| Autor: | Pauline Radreau, Julie Sanderson, Paul A. Kroon, Jeremy D. Rhodes, Richard Mithen |
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| Rok vydání: | 2009 |
| Předmět: |
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Western Flavonoid Lens Capsule Crystalline Chromosomal translocation Biology Antioxidants Cellular and Molecular Neuroscience chemistry.chemical_compound Downregulation and upregulation Gene expression Humans heterocyclic compounds Secretion RNA Messenger Cells Cultured chemistry.chemical_classification Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Epithelial Cells Microarray Analysis Molecular biology Sensory Systems Cell biology Blot Ophthalmology Gene Expression Regulation chemistry Quercetin Hypoxia-Inducible Factor 1 Signal transduction Signal Transduction |
| Zdroj: | Experimental Eye Research. 89:995-1002 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2009.08.011 |
| Popis: | Quercetin is a dietary bioflavonoid which has been shown to inhibit lens opacification in a number of models of cataract. The objectives of this study were to determine gene expression changes in human lens epithelial cells in response to quercetin and to investigate in detail the mechanisms underlying the responses. FHL-124 cells were treated with quercetin (10 microM) and changes in gene expression were measured by microarray. It was found that 65% of the genes with increased expression were regulated by the hypoxia-inducible factor-1 (HIF-1) pathway. Quercetin (10 and 30 microM) induced a time-dependent increase in HIF-1alpha protein levels. Quercetin (30 microM) was also responsible for a rapid and long-lasting translocation of HIF-1alpha from the cytoplasm to the nucleus. Activation of HIF-1 signaling by quercetin was confirmed by qRT-PCR which showed upregulation of the HIF-1 regulated genes EPO, VEGF, PGK1 and BNIP3. Analysis of medium taken from FHL-124 cells showed a sustained dose-dependent increase in VEGF secretion following quercetin treatment. The quercetin-induced increase and nuclear translocation of HIF-1alpha was reversed by addition of excess iron (100 microM). These results demonstrate that quercetin activates the HIF-1 signaling pathway in human lens epithelial cells. |
| Databáze: | OpenAIRE |
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