PUBLICATION
SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway
- Authors
- Zhang, Y., Peng, X., Xue, M., Liu, J., Shang, G., Jiang, M., Chen, D., Liu, B., Wang, Y., Jia, X., Xu, J., Zhang, F., Hu, Y.
- ID
- ZDB-PUB-230205-16
- Date
- 2023
- Source
- Biogerontology 24(5): 813-827 (Journal)
- Registered Authors
- Hu, Yanzhong
- Keywords
- RPE, SARS-Cov-2, Senescence, Spike protein, Zebrafish
- MeSH Terms
-
- Animals
- COVID-19*
- Cellular Senescence/physiology
- Humans
- NF-kappa B/metabolism
- Reactive Oxygen Species/metabolism
- SARS-CoV-2/metabolism
- Spike Glycoprotein, Coronavirus*/metabolism
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- PubMed
- 36738354 Full text @ Biogerontology
Citation
Zhang, Y., Peng, X., Xue, M., Liu, J., Shang, G., Jiang, M., Chen, D., Liu, B., Wang, Y., Jia, X., Xu, J., Zhang, F., Hu, Y. (2023) SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway. Biogerontology. 24(5):813-827.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping