ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Lysosomal alkalinization, lipid oxidation, and reduced phagosome clearance triggered by activation of the P2X7 receptor.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 90 citations in OpenAlex.
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- PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.American journal of physiology. Cell physiology · 2026Article
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- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (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
- P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types.Antioxidants (Basel, Switzerland) · 2023Article
- The phospholipid flippase ATP8B1 is required for lysosomal fusion in macrophages.Cell biochemistry and function · 2022Article
- Tetrandrine ameliorates cognitive deficits and mitigates tau aggregation in cell and animal models of tauopathies.Journal of biomedical science · 2022Article
- Article
- P2X7 Receptor Triggers Lysosomal Leakage Through Calcium Mobilization in a Mechanism Dependent on Pannexin-1 Hemichannels.Frontiers in immunology · 2022Article
- P2X4 Receptors Mediate CaInternational journal of molecular sciences · 2021Article
- Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure.Journal of neuroinflammation · 2021Article
- Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2021Article
- Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.Investigative ophthalmology & visual science · 2021Article
- Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Lysosomal enzymes function optimally at low pH; as accumulation of waste material contributes to cell aging and disease, dysregulation of lysosomal pH may represent an early step in several pathologies. Here, we demonstrate that stimulation of the P2X7 receptor (P2X7R) for ATP alkalinizes lysosomes in cultured human retinal pigmented epithelial (RPE) cells and impairs lysosomal function. P2X7R stimulation did not kill RPE cells but alkalinized lysosomes by 0.3 U. Receptor stimulation also elevated cytoplasmic Ca(2+); Ca(2+) influx was necessary but not sufficient for lysosomal alkalinization. P2X7R stimulation decreased access to the active site of cathepsin D. Interestingly, lysosomal alkalinization was accompanied by a rise in lipid oxidation that was prevented by P2X7R antagonism. Likewise, the autofluorescence of phagocytosed photoreceptor outer segments increased by lysosomal alkalinization was restored 73% by a P2X7R antagonist. Together, this suggests that endogenous autostimulation of the P2X7R may oxidize lipids and impede clearance. The P2X7R was expressed on apical and basolateral membranes of mouse RPE; mRNA expression of P2X7R and extracellular ATP marker NTPDase1 was raised in RPE tissue from the ABCA4(-/-) mouse model of Stargardt's retinal degeneration. In summary, P2X7R stimulation raises lysosomal pH and impedes lysosomal function, suggesting a possible role for overstimulation in diseases of accumulation.
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