ArticlePloS one2017
Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 96 citations in OpenAlex.
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- Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.Antioxidants (Basel, Switzerland) · 2026Article
- Study on the improvement effect and mechanism of resveratrol on cognitive impairment in tau mutant adenovirus-induced alzheimer's disease model mice.Psychopharmacology · 2026Article
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- The Interplay Between the Ubiquitin-Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Selective activation of antioxidant resources and energy deficiency in Marinesco-Sjögren syndrome fibroblasts as an adaptive biological response to Sil1 loss.Scientific reports · 2025Article
- Protein phosphatase 1 regulatory subunit 15 A (PPP1R15A) promoted the progression of gastric cancer by activating cell autophagy under energy stress.Journal of experimental & clinical cancer research : CR · 2025Article
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- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Hypoxia induces ROS-resistant memory upon reoxygenation in vivo promoting metastasis in part via MUC1-C.Nature communications · 2024Article
- Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.Journal of cell science · 2024Article
- Evaluation of Nanoparticles Covalently Bound with BODIPY for Their Photodynamic Therapy Applicability.International journal of molecular sciences · 2024Article
- Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions.International journal of molecular sciences · 2024Review
- αB-Crystallin Peptide Fused with Elastin-like Polypeptide: Intracellular Activity in Retinal Pigment Epithelial Cells Challenged with Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Distinct Roles of CK2- and AKT-Mediated NF-κB Phosphorylations in Clasmatodendrosis (Autophagic Astroglial Death) within the Hippocampus of Chronic Epilepsy Rats.Antioxidants (Basel, Switzerland) · 2023Article
- Antioxidative and Mitochondrial Protection in Retinal Pigment Epithelium: New Light Source in Action.International journal of molecular sciences · 2023Article
- Autophagy in age-related macular degeneration.Autophagy · 2023Review
- Low-Dose Blue Light (420 nm) Reduces Metabolic Activity and Inhibits Proliferation of Human Dermal Fibroblasts.Life (Basel, Switzerland) · 2023Article
- Biomacromolecular Profile in Human Primary Retinal Pigment Epithelial Cells-A Study of Oxidative Stress and Autophagy by Synchrotron-Based FTIR Microspectroscopy.Biomedicines · 2023Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4) mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic) and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection under oxidative stress and functions, in part, by modulating ATG10 expression. NFκB p65 activity may be a critical upstream initiator of p62 expression in RPE cells under oxidative stress.
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