Flavonoids Protect Human Retinal Pigment Epithelial Cells from Oxidative-Stress–Induced Death

Hanneken, Anne; Lin, Fen Fen; Johnson, Jack; Maher, Pamela

doi:10.1167/iovs.04-1369

Cited by 271 publications

(237 citation statements)

References 31 publications

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“…Furthermore, EGCG exerted the protective effects against amyloid beta (Aβ) toxicity in PC12, SH-SHY5Y and mice hippocampus (Levites, Amit, Mandel, & Youdim, 2003). However, the previous study reported that EGCG did not protect against H 2 O 2 -induced oxidative stress in ARPE-19 cells (Hanneken, Lin, Johnson, & Maher, 2006), a finding which was not consistent with our study. This disparity may be due to differences in experimental procedure; in their studies ARPE-19 cells were exposed to H 2 O 2 for a period of time before adding the EGCG, cell density and concentrations of EGCG used in their experiments were lower.…”

Section: Effect Of H 2 O 2 Egcg and Caspase 3 Inhibitor On Arpe-19contrasting

confidence: 99%

“…Previous studies were reported that EGCG also has protective effects against apoptosis induced by the pro-parkinsonian neurotoxin 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells (Guo, Bezard, & Zhao, 2005). It has also been reported that certain flavanoids including EGCG protected RPE cells from oxidative stress induce cell death (Hanneken et al, 2006) by inducing the expression of transcription factor Nrf2 (Nuclear factor-erythroid 2-related factor-2) and phase 2 enzyme heme-oxygenase, suggesting that EGCG afforded protection via its antioxidant properties. However, a direct action of EGCG on the apoptotic pathway in ARPE-19 cells has not been demonstrated.…”

Section: Effect Of H 2 O 2 Egcg and Caspase 3 Inhibitor On Arpe-19mentioning

confidence: 99%

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Green Tea epigallocatechin-3-gallate Protects Against Oxidative Stress-Induced Nuclear Translocation of p53 and Apoptosis in Retinal Pigment Epithelial Cells, ARPE-19

Thichanpiang¹,

Khanobdee²,

Kitiyanant³

et al. 2013

JAS

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Epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic flavonoids in green tea has been shown to possess strong antioxidant activities. Oxidative stress causes the defect of retinal pigment epithelial (RPE) cells that contribute to several retinal diseases. Several studies have shown that increasing the body's defenses against oxidative stress with specific antioxidants and mineral supplements could preserve the vision. Therefore, the purpose of this study was to determine the protective role of EGCG against exogenous reactive oxygen species hydrogen peroxide (H 2 O 2 )-induced cell death in ARPE-19 cells, human retinal pigment epithelial cell line. ARPE-19 cells were pretreated with EGCG in the presence/absence of H 2 O 2 . The protective effects of EGCG and the underlined mechanisms against H 2 O 2 were evaluated. The present study demonstrated that 400 µM H 2 O 2 significantly decreased cell viability, increased the accumulation of intracellular reactive oxygen species (ROS) and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells and chromatin condensed nuclei. In addition, H 2 O 2 induced p53 nuclear translocation, up-regulated Bax and down-regulated Bcl-2 expression thereby increased Bax/Bcl-2 ratio. These toxic effects of H 2 O 2 were reversed by 100 µM EGCG pretreatment. These studies suggest that EGCG protects H 2 O 2 -induced cell death in ARPE-19 cells by its antioxidant property and attenuation of p53 nuclear translocation.

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Section: Effect Of H 2 O 2 Egcg and Caspase 3 Inhibitor On Arpe-19contrasting

confidence: 99%

Section: Effect Of H 2 O 2 Egcg and Caspase 3 Inhibitor On Arpe-19mentioning

confidence: 99%

Green Tea epigallocatechin-3-gallate Protects Against Oxidative Stress-Induced Nuclear Translocation of p53 and Apoptosis in Retinal Pigment Epithelial Cells, ARPE-19

Thichanpiang¹,

Khanobdee²,

Kitiyanant³

et al. 2013

JAS

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“…First, flavonoids can protect nerve cells from oxidative stress-induced death by both acting as a direct antioxidant and by maintaining high levels of glutathione (GSH), the major intracellular antioxidant (Ishige et al, 2001). Second, multiple studies have shown that certain flavonoids can induce the activity and expression of phase II detoxification proteins (Hanneken et al, 2006;Hou et al, 2001;Maher and Hanneken, 2005b;Maher, 2006;Myhrstad et al, 2002;Valerio et al, 2001). The phase II detoxification proteins include enzymes associated with glutathione biosynthesis and metabolism and redox sensitive proteins such as heme oxygenase 1 (HO-1) (Hayes and McLellan, 1999).…”

Section: Introductionmentioning

confidence: 99%

A novel approach to screening for new neuroprotective compounds for the treatment of stroke

et al. 2007

Self Cite

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Despite the significant advances that have been made in understanding the pathophysiology of cerebral ischemia on the cellular and molecular level, only one drug, the thrombolytic tissue plasminogen activator (rt-PA), is approved by the FDA for use in patients with acute ischemic stroke. Therefore, there is a critical need for additional safe and effective treatments for stroke. In order to identify novel compounds that might be effective, we have developed a cell culture-based assay with death being an endpoint as a screening tool. We have performed an initial screening for potential neuroprotective drugs among a group of flavonoids by using the mouse hippocampal cell line, HT22, in combination with chemical ischemia. Further screens were provided by biochemical assays for ATP and glutathione, the major intracellular antioxidant, as well as for long-term induction of antioxidant proteins. Based upon the results of these screens, we tested the best flavonoid, fisetin, in the small clot embolism model of cerebral ischemia in rabbits. Fisetin significantly reduced the behavioral deficits following a stroke, providing proof of principle for this novel approach to identifying new compounds for the treatment of stroke.

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“…Much research in this area has focussed on stimulation of antioxidant defences via the transcription factor Nrf-2 acting at the antioxidant response element (ARE) (Li and Kong, 2009) and quercetin has been shown to stimulate this pathway (Hanneken et al, 2006). However, a number of other pathways have also been shown to be upregulated by the flavonoid in a variety of cell types (Gong et al, 2009;Jeong et al, 2009;Kampkotter et al, 2008;Triantafyllou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells

Radreau

Rhodes

Mithen

et al. 2009

Experimental Eye Research

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Keywords: quercetin flavonoid antioxidant diet lens HIF-1a hypoxia VEGF a b s t r a c t 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 mM) 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 mM) induced a time-dependent increase in HIF-1a protein levels. Quercetin (30 mM) was also responsible for a rapid and long-lasting translocation of HIF-1a 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-1a was reversed by addition of excess iron (100 mM). These results demonstrate that quercetin activates the HIF-1 signaling pathway in human lens epithelial cells.

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Flavonoids Protect Human Retinal Pigment Epithelial Cells from Oxidative-Stress–Induced Death

Cited by 271 publications

References 31 publications

Green Tea epigallocatechin-3-gallate Protects Against Oxidative Stress-Induced Nuclear Translocation of p53 and Apoptosis in Retinal Pigment Epithelial Cells, ARPE-19

Green Tea epigallocatechin-3-gallate Protects Against Oxidative Stress-Induced Nuclear Translocation of p53 and Apoptosis in Retinal Pigment Epithelial Cells, ARPE-19

A novel approach to screening for new neuroprotective compounds for the treatment of stroke

Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells

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