ArticleRedox biology2016
The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation.
Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
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- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Disruption of the KLHL37-N-Myc complex restores N-Myc degradation and arrests neuroblastoma growth in mouse models.The Journal of clinical investigation · 2025Article
- Omaveloxolone Ameliorates Cognitive Deficits by Inhibiting Apoptosis and Neuroinflammation in APP/PS1 Mice.Molecular neurobiology · 2025Article
- RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway.Open life sciences · 2025Article
- Omaveloxolone promotes functional recovery of spinal cord injury by reducing inflammatory response and regulating macrophage polarization.Frontiers in molecular neuroscience · 2025Article
- Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.Biomolecules & therapeutics · 2024Article
- Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.Aging and disease · 2024Review
- Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.International journal of ophthalmology · 2024Review
- Oxidative stress and ion channels in neurodegenerative diseases.Frontiers in physiology · 2024Review
- Review
- Dependence of Retinal Pigment Epithelium Integrity on the NRF2-Heme Oxygenase-1 Axis.Investigative ophthalmology & visual science · 2022Article
- In Vitro Efficacy and Molecular Mechanism of Curcumin Analog in Pathological Regulation of Spinocerebellar Ataxia Type 3.Antioxidants (Basel, Switzerland) · 2022Article
- Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury.Cell death & disease · 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
- The Novel Nrf2 Activator Omaveloxolone Regulates Microglia Phenotype and Ameliorates Secondary Brain Injury after Intracerebral Hemorrhage in Mice.Oxidative medicine and cellular longevity · 2022Article
- Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets.Science China. Life sciences · 2021Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD). Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200μM H2O2 for 6h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining and Hoechst 33342 fluorescent staining. Reduced (GSH) and oxidized glutathione (GSSG) were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100nM) of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.
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