ArticlePloS one2014
Proteasome inhibitors activate autophagy involving inhibition of PI3K-Akt-mTOR pathway as an anti-oxidation defense in human RPE cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Copper Overload Affects α-Synuclein Clearance Mechanisms in a Parkinson's Disease In Vitro Model.Advanced biology · 2026Article
- The Interplay Between the Ubiquitin-Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Grape Seed Proanthocyanidins Mitigate Acute High-Altitude Hypoxia-Induced Brain Injury by Inhibiting NLRP3 Inflammasome via Autophagy Pathway.Molecular neurobiology · 2025Article
- Low-level red light inhibits human retinal pigment epithelial cell fibrosis via UBE2C in a myopia-simulating hypoxic microenvironment.European journal of medical research · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.International journal of molecular sciences · 2023Review
- Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022Review
- Targeting autophagy increases the efficacy of proteasome inhibitor treatment in multiple myeloma by induction of apoptosis and activation of JNK.BMC cancer · 2022Article
- Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases.Acta pharmaceutica Sinica. B · 2021Review
- Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Age Related Macular Degeneration, Role in Pathophysiology, and Possible New Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2021Review
- Immunosubunit β5i Knockout Suppresses Neovascularization and Restores Autophagy in Retinal Neovascularization by Targeting ATG5 for Degradation.Investigative ophthalmology & visual science · 2020Article
- Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.Cancer science · 2020Article
- Angelicin-A Furocoumarin Compound With Vast Biological Potential.Frontiers in pharmacology · 2020Review
- Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration.Oxidative medicine and cellular longevity · 2020Review
- Autophagy in Age-Related Macular Degeneration: A Regulatory Mechanism of Oxidative Stress.Oxidative medicine and cellular longevity · 2020Review
- Article
- Autophagy contributes to BMP type 2 receptor degradation and development of pulmonary arterial hypertension.The Journal of pathology · 2019Article
- Susceptibility of microtubuleFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Proteasome Activation as a New Therapeutic Approach To Target Proteotoxic Disorders.Journal of medicinal chemistry · 2019Review
- The Role of Primary Cilia in the Crosstalk between the Ubiquitin⁻Proteasome System and Autophagy.Cells · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The two major intracellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, work collaboratively in many biological processes including development, apoptosis, aging, and countering oxidative injuries. We report here that, in human retinal pigment epithelial cells (RPE), ARPE-19 cells, proteasome inhibitors, clasto-lactacystinβ-lactone (LA) or epoxomicin (Epo), at non-lethal doses, increased the protein levels of autophagy-specific genes Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light chain (LC3) from LC3-I to its lipidative form, LC3-II, which was enhanced by co-addition of the saturated concentration of Bafilomycin A1 (Baf). Detection of co-localization for LC3 staining and labeled-lysosome further confirmed autophagic flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein kinase B (Akt), a downstream target of phosphatidylinositol-3-kinases (PI3K), and mammalian target of rapamycin (mTOR) in ARPE-19 cells; by contrast, the induced changes of autophagy substrate, p62, showed biphasic pattern. The autophagy inhibitor, Baf, attenuated the reduction in oxidative injury conferred by treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione (VK3) or 4-hydroxynonenal (4-HNE). Knockdown of Atg7 with siRNA in ARPE-19 cells reduced the protective effects of LA or Epo against VK3. Overall, our results suggest that treatment with low levels of proteasome inhibitors confers resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt-mTOR pathway and activation of autophagy.
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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.