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The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression.
Invest Ophthalmol Vis Sci. 2009 May; 50(5):2398-406.IO

Abstract

PURPOSE

Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. The present study sought to determine whether eriodictyol-induced phase 2 protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress.

METHODS

The ability of eriodictyol to activate Nrf2 and to induce the phase 2 proteins heme-oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1, and the cellular antioxidant glutathione (GSH) were analyzed. Cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1 were performed, cell survival after short-term and long-term eriodictyol treatment was compared, and the mechanism of protection using a dominant negative Nrf2 and shRNA specific for HO-1 was tested.

RESULTS

Eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of HO-1 and NQO-1, and increased the levels of intracellular glutathione. ARPE-19 cells that overexpress HO-1 or NQO-1 were more resistant to oxidative stress-induced cell death than control cells. Eriodictyol induced long-term protection significantly greater than its short-term protection. This effect was correlated temporally with the activation of Nrf2 and the induction of phase 2 enzymes and could be blocked with the use of a dominant negative Nrf2 and shRNA specific to HO-1.

CONCLUSIONS

These findings indicate that the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury.

Authors+Show Affiliations

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19117929

Citation

Johnson, Jennifer, et al. "The Flavonoid, Eriodictyol, Induces Long-term Protection in ARPE-19 Cells Through Its Effects On Nrf2 Activation and Phase 2 Gene Expression." Investigative Ophthalmology & Visual Science, vol. 50, no. 5, 2009, pp. 2398-406.
Johnson J, Maher P, Hanneken A. The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. Invest Ophthalmol Vis Sci. 2009;50(5):2398-406.
Johnson, J., Maher, P., & Hanneken, A. (2009). The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. Investigative Ophthalmology & Visual Science, 50(5), 2398-406. https://doi.org/10.1167/iovs.08-2088
Johnson J, Maher P, Hanneken A. The Flavonoid, Eriodictyol, Induces Long-term Protection in ARPE-19 Cells Through Its Effects On Nrf2 Activation and Phase 2 Gene Expression. Invest Ophthalmol Vis Sci. 2009;50(5):2398-406. PubMed PMID: 19117929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The flavonoid, eriodictyol, induces long-term protection in ARPE-19 cells through its effects on Nrf2 activation and phase 2 gene expression. AU - Johnson,Jennifer, AU - Maher,Pamela, AU - Hanneken,Anne, Y1 - 2008/12/30/ PY - 2009/1/2/entrez PY - 2009/1/2/pubmed PY - 2009/5/13/medline SP - 2398 EP - 406 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 50 IS - 5 N2 - PURPOSE: Eriodictyol, a flavonoid found in citrus fruits, is among the most potent compounds reported to protect human RPE cells from oxidative stress-induced cell death. The present study sought to determine whether eriodictyol-induced phase 2 protein expression further enhances the resistance of human ARPE-19 cells to oxidative stress. METHODS: The ability of eriodictyol to activate Nrf2 and to induce the phase 2 proteins heme-oxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1, and the cellular antioxidant glutathione (GSH) were analyzed. Cytoprotection assays in ARPE-19 cells that were overexpressing HO-1 or NQO-1 were performed, cell survival after short-term and long-term eriodictyol treatment was compared, and the mechanism of protection using a dominant negative Nrf2 and shRNA specific for HO-1 was tested. RESULTS: Eriodictyol induced the nuclear translocation of Nrf2, enhanced the expression of HO-1 and NQO-1, and increased the levels of intracellular glutathione. ARPE-19 cells that overexpress HO-1 or NQO-1 were more resistant to oxidative stress-induced cell death than control cells. Eriodictyol induced long-term protection significantly greater than its short-term protection. This effect was correlated temporally with the activation of Nrf2 and the induction of phase 2 enzymes and could be blocked with the use of a dominant negative Nrf2 and shRNA specific to HO-1. CONCLUSIONS: These findings indicate that the greatest benefit from eriodictyol may be its ability to regulate gene expression and enhance multiple cellular defenses to oxidative injury. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/19117929/The_flavonoid_eriodictyol_induces_long_term_protection_in_ARPE_19_cells_through_its_effects_on_Nrf2_activation_and_phase_2_gene_expression_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.08-2088 DB - PRIME DP - Unbound Medicine ER -