ArticleBiogerontology2023
SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway.
Article in Biogerontology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- NEAT1 drives SARS-CoV-2 N protein-induced inflammation, metabolic reprogramming, and mitochondria-ER stress crosstalk.Scientific reports · 2026Article
- Synthetic Integration of an FCS into Coronaviruses-Hype or an Unresolved Biorisk? An Integrative Analysis of DNA Repair, Cancer Research, Drug Development, and Escape Mutant Traits.Life (Basel, Switzerland) · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- Viral mechanisms, tropism, and clinical relevance regarding the ophthalmic manifestations of SARS-CoV-2 infection.International journal of ophthalmology · 2026Review
- Integrated genomics reveals cellular senescence-driven molecular networks and immune crosstalk in myopia pathogenesis.Journal of cell communication and signaling · 2025Article
- Basic implications on three pathways associated with SARS-CoV-2.Biomedical journal · 2025Review
- Network Pharmacology and Experimental Validation to Elucidate the Pharmacological Mechanisms of Luteolin Against Chondrocyte Senescence.Combinatorial chemistry & high throughput screening · 2025Article
- Neratinib stimulates senescence of mammary cancer cells by reducing the levels of SIRT1.Aging · 2024Article
- Article
- Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration.Molecular neurodegeneration · 2024Review
- Triiodothyronine acts on DAO to regulate pulmonary fibrosis progression by facilitating cell senescence through the p53/p21 signaling pathway.Frontiers in pharmacology · 2024Article
- Fullerenol CInternational journal of nanomedicine · 2024Article
- Article
- HO-1-Mediated Autophagic Restoration Protects Lens Epithelial Cells Against Oxidative Stress and Cellular Senescence.Investigative ophthalmology & visual science · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-β-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1β, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κb. These results may uncover a potential association between SARS-cov-2 infection and development of AMD.
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