ArticleInvestigative ophthalmology & visual science2008
The proteasome: a target of oxidative damage in cultured human retina pigment epithelial cells.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Proteasome and Ribosome Ubiquitination in Retinal Pigment Epithelial (RPE) Cells in Response to Oxidized Low-Density Lipoprotein (OxLDL).Biomedicines · 2025Article
- Features that distinguish age-related macular degeneration from aging.Experimental eye research · 2025Review
- Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.International journal of molecular sciences · 2023Review
- The role of amyloid β in the pathological mechanism of GNE myopathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Photobiology of lipofuscin granules in the retinal pigment epithelium cells of the eye: norm, pathology, age.Biophysical reviews · 2022Review
- Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2021Article
- Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Age Related Macular Degeneration, Role in Pathophysiology, and Possible New Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2021Review
- Oxidative Inactivation of the Proteasome Augments Alveolar Macrophage Secretion of Vesicular SOCS3.Cells · 2020Article
- Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning.Biomolecules · 2020Review
- Mesenchymal Stem Cell Secretome Enhancement by Nicotinamide and Vasoactive Intestinal Peptide: A New Therapeutic Approach for Retinal Degenerative Diseases.Stem cells international · 2020Article
- Measuring redox effects on the activities of intracellular proteases such as the 20S Proteasome and the Immuno-Proteasome with fluorogenic peptides.Free radical biology & medicine · 2019Article
- C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway.Scientific reports · 2018Article
- Root hydrotropism and thigmotropism in Arabidopsis thaliana are differentially controlled by redox status.Plant signaling & behavior · 2017Article
- Docosahexaenoic acid-mediated protein aggregates may reduce proteasome activity and delay myotube degradation during muscle atrophy in vitro.Experimental & molecular medicine · 2017Article
- Proteotoxic Stress Desensitizes TGF-beta Signaling Through Receptor Downregulation in Retinal Pigment Epithelial Cells.Current molecular medicine · 2017Article
- Inhibition of Protein Ubiquitination by Paraquat and 1-Methyl-4-Phenylpyridinium Impairs Ubiquitin-Dependent Protein Degradation Pathways.Molecular neurobiology · 2016Article
- Hydrogen Peroxide-Induced Oxidative Stress Activates Proteasomal Trypsin-Like Activity in Human U373 Glioma Cells.Journal of molecular neuroscience : MN · 2016Article
- Redox control of protein degradation.Redox biology · 2015Review
- Correlations between Photodegradation of Bisretinoid Constituents of Retina and Dicarbonyl Adduct Deposition.The Journal of biological chemistry · 2015Article
- Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.Seminars in immunopathology · 2015Review
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeDysfunction of the ubiquitin-proteasome pathway (UPP) is associated with several age-related degenerative diseases. The objective of this study was to investigate the effect of oxidative stress on the UPP in cultured human retina pigment epithelial cells.
methodsTo mimic physiological oxidative stress, ARPE-19 cells were exposed to continuously generated H2O(2) or A2E-mediated photooxidation. Proteasome activity was monitored using fluorogenic peptides as substrates. The ubiquitin conjugation activity and activities of E1 and E2 were determined by the thiolester assays. Levels of ubiquitin and ubiquitin conjugates were determined by Western blotting.
resultsExposure of ARPE-19 cells to 40 to 50 microM H2O(2) for 4 hours resulted in a 30% to 50% reduction in all three peptidase activities of the proteasome. Similarly, exposure of A2E-loaded ARPE-19 cells to blue light resulted in a 40% to 60% reduction in proteasome activity. Loading of A2E or exposure to blue light alone had little effect on proteasome activity. In contrast, exposure of ARPE-19 to low levels of H2O(2) (10 microM) stimulated ubiquitin conjugation activity. Loading of A2E, with or without exposure to blue light, upregulated the levels of ubiquitin-activating enzyme and increased conjugation activity. Exposure to H2O(2) or A2E-mediated photooxidation also resulted in a twofold to threefold increase in levels of endogenous ubiquitin conjugates.
conclusionsThese data show that the proteasome in ARPE-19 is susceptible to oxidative inactivation, whereas activities of the ubiquitin-conjugating enzymes are more resistant to oxidative stress. Oxidative inactivation of the proteasome appears to be one of the mechanisms underlying stress-induced accumulation of ubiquitin conjugates in the cells.
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