ArticleBiochimica et biophysica acta2014
p62 provides dual cytoprotection against oxidative stress in the retinal pigment epithelium.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.Diagnostics (Basel, Switzerland) · 2024Review
- Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.Aging and disease · 2024Review
- Oxidative stress in the eye and its role in the pathophysiology of ocular diseases.Redox biology · 2023Review
- Antioxidative Role of Heterophagy, Autophagy, and Mitophagy in the Retina and Their Association with the Age-Related Macular Degeneration (AMD) Etiopathogenesis.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy.Biomolecules · 2023Review
- Autophagy in age-related macular degeneration.Autophagy · 2023Review
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- A Gedunin-Type Limonoid, 7-Deacetoxy-7-Oxogedunin, from Andiroba (International journal of molecular sciences · 2022Article
- Programmed Cell Death and Autophagy in anFrontiers in neuroanatomy · 2022Article
- Plasma Rich in Growth Factors Promotes Autophagy in ARPE19 Cells in Response to Oxidative Stress Induced by Blue Light.Biomolecules · 2021Article
- Review
- Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation.International journal of molecular sciences · 2021Article
- Mitochondria-dependent phase separation of disease-relevant proteins drives pathological features of age-related macular degeneration.JCI insight · 2021Article
- Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor.Biology · 2021Article
- MicroRNA-100 Mediates Hydrogen Peroxide-Induced Apoptosis of Human Retinal Pigment Epithelium ARPE-19 Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The Role of Autophagy in Eye Diseases.Life (Basel, Switzerland) · 2021Review
- Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels.International journal of molecular sciences · 2021Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
As a signaling hub, p62/sequestosome plays important roles in cell signaling and degradation of misfolded proteins. p62 has been implicated as an adaptor protein to mediate autophagic clearance of insoluble protein aggregates in age-related diseases, including age-related macular degeneration (AMD), which is characterized by dysfunction of the retinal pigment epithelium (RPE). Our previous studies have shown that cigarette smoke (CS) induces oxidative stress and inhibits the proteasome pathway in cultured human RPE cells, suggesting that p62-mediated autophagy may become the major route to remove impaired proteins under such circumstances. In the present studies, we found that all p62 mRNA variants are abundantly expressed and upregulated by CS induced stress in cultured human RPE cells, yet isoform1 is the major translated form. We also show that p62 silencing exacerbated the CS induced accumulation of damaged proteins, both by suppressing autophagy and by inhibiting the Nrf2 antioxidant response, which in turn, increased protein oxidation. These effects of CS and p62 reduction were further confirmed in mice exposed to CS. We found that over-expression of p62 isoform1, but not its S403A mutant, which lacks affinity for ubiquitinated proteins, reduced misfolded proteins, yet simultaneously promoted an Nrf2-mediated antioxidant response. Thus, p62 provides dual, reciprocal enhancing protection to RPE cells from environmental stress induced protein misfolding and aggregation, by facilitating autophagy and the Nrf2 mediated antioxidant response, which might be a potential therapeutic target against AMD.
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