ArticleInvestigative ophthalmology & visual science2015
4-Acetoxyphenol Prevents RPE Oxidative Stress-Induced Necrosis by Functioning as an NRF2 Stabilizer.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Stages, pathogenesis, clinical management and advancements in therapies of age-related macular degeneration.International ophthalmology · 2023Review
- Evaluation of the role of Sigma 1 receptor and Cullin3 in retinal photoreceptor cells.Free radical biology & medicine · 2023Article
- Molecular Mechanisms of Oxidative Stress Relief by CAPE in ARPE-19 Cells.International journal of molecular sciences · 2023Article
- The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways.Foods (Basel, Switzerland) · 2022Article
- Downregulation of Inflammatory Response via Nrf2/Trx1/TXNIP Axis in Oxidative Stress-Induced ARPE-19 Cells and Mouse Model of AMD.Oxidative medicine and cellular longevity · 2022Article
- Comparison of Sigma 1 Receptor Ligands SA4503 and PRE084 to (+)-Pentazocine in the rd10 Mouse Model of RP.Investigative ophthalmology & visual science · 2020Article
- Piceatannol inhibits pyroptosis and suppresses oxLDL-induced lipid storage in macrophages by regulating miR-200a/Nrf2/GSDMD axis.Bioscience reports · 2020Article
- Epigallocatechin 3-Gallate Has a Neuroprotective Effect in Retinas of Rabbits with Ischemia/Reperfusion through the Activation of Nrf2/HO-1.International journal of molecular sciences · 2020Article
- Crocetin Prevents RPE Cells from Oxidative Stress through Protection of Cellular Metabolic Function and Activation of ERK1/2.International journal of molecular sciences · 2020Article
- Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases.International journal of molecular sciences · 2020Article
- Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update.Oxidative medicine and cellular longevity · 2020Review
- Article
- The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.Free radical biology & medicine · 2019Article
- Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration.Cell biology and toxicology · 2017Review
- Taxifolin protects RPE cells against oxidative stress-induced apoptosis.Molecular vision · 2017Article
- Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region.Oncotarget · 2016Article
- Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress.Oxidative medicine and cellular longevity · 2016Article
- Retinal pigment epithelial cell necroptosis in response to sodium iodate.Cell death discovery · 2016Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeOxidative stress has been suggested to be a major risk factor for the pathogenesis of AMD. Retinal pigment epithelial (RPE) cells are essential for maintaining the homeostasis of the retina, and RPE cell death and the resultant photoreceptor apoptosis have been observed in dry AMD, especially in geographic atrophy. The purpose of this article was to identify and repurpose the Food and Drug Administration-approved natural compound 4-Acetoxyphenol (4-AC), and to evaluate its effect and mechanism in protecting against oxidative stress-induced RPE necrosis.
methodsWe exposed ARPE-19 cells to tert-Butyl hydroperoxide (tBHP) after pretreatment with 4-AC, and measured cell viability by MTT assay. Aggregation of RIPK3 and HMGB1 nuclear release were analyzed by transfected reporter genes. Reactive oxygen species (ROS) were measured using a commercially available ROS detection system. The importance of the NRF2/NQO1/HO-1 pathway in mediating 4-AC function was corroborated by siRNA studies, qRT-PCR, and immunostaining.
resultsWe have identified a natural antioxidant, 4-AC, which demonstrates strong abilities to protect RPE cells from oxidative stress-induced necrosis. Mechanistically, 4-AC blocked the increase of cellular ROS induced by oxidative stress, and upregulated NQO1 and HO-1 genes by stabilizing and inducing the nuclear translocation of NRF2 transcription factor. The NQO1, HO-1, and NRF2 were further shown to be required for 4-AC protection of RPE cells from death induced by tBHP. The tBHQ, an NRF2 stabilizer, consistently mimicked the protective effect of 4-AC against tBHP-induced RPE death.
conclusionsThe compound 4-AC protects ARPE-19 cells from oxidative stress-induced necrosis through upregulation of NQO1 and HO-1 genes by stabilization of NRF2.
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