ArticleAutophagy2015
The marine n-3 PUFA DHA evokes cytoprotection against oxidative stress and protein misfolding by inducing autophagy and NFE2L2 in human retinal pigment epithelial cells.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 95 citations in OpenAlex.
- Baicalin Protects ARPE-19 Cells Against BRVO-Related Hypoxic Injury by Preserving Mitochondrial Function and Inhibiting Ferroptosis.Antioxidants (Basel, Switzerland) · 2026Article
- The role of NRF2 function and regulation in atherosclerosis: an update.Molecular and cellular biochemistry · 2025Review
- Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.International journal of molecular sciences · 2025Review
- Senior-Loken Syndrome: Ocular Perspectives on Genetics, Pathogenesis, and Management.Biomolecules · 2025Review
- Blue Light Damages Retinal Ganglion Cells Via Endoplasmic Reticulum Stress and Autophagy in Chickens.Investigative ophthalmology & visual science · 2025Article
- Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway.Acta biochimica et biophysica Sinica · 2024Article
- Evaluation of inflammatory hyperreflective foci and plasma EPA as diagnostic and predictive markers for age-related macular degeneration.Frontiers in neuroscience · 2024Article
- Oxidative stress and docosahexaenoic acid injury lead to increased necroptosis and ferroptosis in retinal pigment epithelium.Scientific reports · 2023Article
- Research trends in the field of retinitis pigmentosa from 2002 to 2021: a 20 years bibliometric analysis.International ophthalmology · 2023Article
- The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy.Biomolecules · 2023Review
- MicroRNAs as the critical regulators of autophagy-mediated cisplatin response in tumor cells.Cancer cell international · 2023Review
- Docosahexaenoic acid enhances hippocampal insulin sensitivity to promote cognitive function of aged rats on a high-fat diet.Journal of advanced research · 2023Article
- Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.Pharmaceutics · 2023Review
- Autophagy in age-related macular degeneration.Autophagy · 2023Review
- Potential Properties of Natural Nutraceuticals and Antioxidants in Age-Related Eye Disorders.Life (Basel, Switzerland) · 2022Review
- Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells.European journal of nutrition · 2022Article
- Oxidized low-density lipoprotein causes ribosome reduction and inhibition of protein synthesis in retinal pigment epithelial cells.Biochemistry and biophysics reports · 2022Article
- Decreased Levels of Erythrocyte Membrane Arachidonic and Docosahexaenoic Acids Are Associated With Retinopathy of Prematurity.Investigative ophthalmology & visual science · 2022Observational
- Nature-Inspired Hybrids (NIH) Improve Proteostasis by Activating Nrf2-Mediated Protective Pathways in Retinal Pigment Epithelial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Potential Suicide Prophylactic Activity by the Fish Oil Metabolite, 4-Hydroxyhexenal.International journal of molecular sciences · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.