ArticlePloS one2015
Role of Glutathione Peroxidase 4 in Glutamate-Induced Oxytosis in the Retina.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 26 citations in OpenAlex.
- Ferroptosis and retinal ganglion cell death in glaucoma: Mechanisms and therapeutic approaches.Journal of pharmaceutical analysis · 2026Review
- Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration.Biomedicines · 2025Review
- Glutathione PeroxidaseGenes · 2023Article
- Ferroptosis and glaucoma: implications in retinal ganglion cell damage and optic nerve survival.Neural regeneration research · 2023Article
- Ferrostatin-1 alleviates tissue and cell damage in diabetic retinopathy by improving the antioxidant capacity of the XcCell death discovery · 2022Article
- Effect of Supplementing Different Levels of L-Glutamine on Holstein Calves during Weaning.Antioxidants (Basel, Switzerland) · 2022Article
- SiOToxicology research · 2022Article
- Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration.Aging and disease · 2021Review
- Ferroptosis: mechanisms and links with diseases.Signal transduction and targeted therapy · 2021Review
- Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis.Nature communications · 2019Article
- Neuroretinal Apoptosis as a Vascular Dysfunction in Diabetic Patients.Current neuropharmacology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of the present study was to investigate the role of glutathione peroxidase 4 (GPx4) in glutamate-induced oxytosis in the retina.
methodsFor in vitro studies, an immortalized rat retinal precursor cell line R28 was used. Cells were transfected with siRNA specifically silencing GPx4 or with scrambled control siRNA. Lipid peroxidation was evaluated by 4-hydroxy-2-nonenal (4-HNE) immunostaining. Cytotoxicity and cell death were evaluated using an LDH activity assay and annexin V staining, respectively. Cells transfected with GPx4 siRNA or control siRNA were treated with glutamate (1 or 2 mM), and the cytotoxicity was evaluated using the LDH activity assay. For in vivo studies, retinal ganglion cell damage was induced by intravitreal injection of 25-mM N-methyl-D-aspartate (NMDA, 2 μL/eye) in GPx4+/+ and GPx4+/- mice. The evaluation of lipid peroxidation (4-HNE immunostaining), apoptosis (TUNEL staining), and cell density in the ganglion cell layer (GCL) were performed at 12 h, 1 day, and 7 days after the NMDA injection.
resultsGPx4 knockdown significantly increased LDH activity by 13.9-fold (P < 0.01) and increased peroxidized lipid levels by 3.2-fold in R28 cells (P < 0.01). In cells transfected with scrambled control siRNA, treatment with glutamate at 1 or 2 mM did not increase LDH activity; whereas, in cells transfected with GPx4 siRNA, glutamate treatment significantly increased LDH activity (1.52-fold, P < 0.01). GPx4+/- mice exhibited higher levels of lipid peroxidation in retinas treated with NMDA than GPx4+/+ mice (1.26-fold, P < 0.05). GPx4+/- mice had more TUNEL-positive cells induced by NMDA in GCL (1.45-fold, P < 0.05). In addition, the cell density in GCL of GPx4+/- mice was 19% lower than that in GPx4+/+ mice after treatment with NMDA (P < 0.05).
conclusionThese results suggest that defective GPx4 expression is associated with enhanced cytotoxicity by glutamate-induced oxytosis in the retina.
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