ArticleJournal of cellular and molecular medicine2009
Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells.
Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 3 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Guideline
- Neuronal death and accumulation of lipid droplets and glycogen granules within retinal pigment epithelium under the influence of mTOR and autophagy.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- The Interplay Between the Ubiquitin-Proteasome System and Oxidative Stress: A Future Perspective in Eye Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential.Journal of pharmaceutical analysis · 2025Review
- Modulation of mTOR Within Retinal Pigment Epithelium Affects Cell Viability and Mitochondrial Pathology.International journal of molecular sciences · 2025Article
- Article
- Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells.Archives of toxicology · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- Lysosomes in retinal health and disease.Trends in neurosciences · 2023Review
- Stages, pathogenesis, clinical management and advancements in therapies of age-related macular degeneration.International ophthalmology · 2023Review
- Cellular and Molecular Triggers of Retinal Regeneration in Amphibians.Life (Basel, Switzerland) · 2023Review
- 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 Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy.Biomolecules · 2023Review
- Article
- Nerve Growth Factor-Based Therapy in Alzheimer's Disease and Age-Related Macular Degeneration.Frontiers in neuroscience · 2021Review
- An In-Vitro Cell Model of Intracellular Protein Aggregation Provides Insights into RPE Stress Associated with Retinopathy.International journal of molecular sciences · 2020Article
- A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals.International journal of molecular sciences · 2020Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells.
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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.