Jennifer Johnson1, Pamela Maher, Anne Hanneken. 1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
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.
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 humanARPE-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: Yee Y Lee-Hilz; Anne-Marie J F Boerboom; Adrie H Westphal; Willem J H van Berkel; Jac M M J G Aarts; Ivonne M C M Rietjens Journal: Chem Res Toxicol Date: 2006-11 Impact factor: 3.739
Authors: Paul E Milbury; Brigitte Graf; Joanne M Curran-Celentano; Jeffrey B Blumberg Journal: Invest Ophthalmol Vis Sci Date: 2007-05 Impact factor: 4.799
Authors: Grant Quiller; Ángel Mérida-Ortega; Stephen J Rothenberg; Mariano E Cebrián; A Jay Gandolfi; Francisco Franco-Marina; Lizbeth López-Carrillo Journal: Nutr Res Date: 2018-04-21 Impact factor: 3.315
Authors: G Sowmya Shree; K Yogendra Prasad; H S Arpitha; U R Deepika; K Nawneet Kumar; Priya Mondal; P Ganesan Journal: Mol Cell Biochem Date: 2017-05-26 Impact factor: 3.396