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Mitomycin induces alveolar epithelial cell senescence by down-regulating GSK3β signaling
- Source :
- Toxicology letters. 352
- Publication Year :
- 2021
-
Abstract
- Mitomycin treatment induces pulmonary toxicity, and alveolar epithelial cell senescence is crucial in the pathogenesis of the latter. However, the mechanism by which mitomycin induces alveolar epithelial cell senescence has yet to be elucidated. In this work, different doses (37.5-300 nM) of mitomycin induced the senescence of human alveolar type II-like epithelial cells and enhanced the phosphorylation of GSK3β (S9). The GSK3β (S9A) mutant reversed the senescence of mitomycin-treated alveolar epithelial cells. Pharmacological inhibition and gene deletion of Akt1, a kinase that regulates the phosphorylation of GSK3β (S9), suppressed mitomycin-induced alveolar epithelial cell senescence. The knockdown of p53, a downstream effector of GSK3β and an important regulator of cell senescence, repressed mitomycin-induced alveolar epithelial cell senescence. Treatment with baicalein weakened the phosphorylation of GSK3β (S9) and alleviated the senescence of alveolar epithelial cells brought about by mitomycin treatment. GSK3β (S9) phosphorylation appears to be the first signal involved in the mitomycin-induced senescence of alveolar epithelial cells and may present a potential target for attenuating mitomycin-induced pulmonary toxicity.
- Subjects :
- Senescence
Alkylating Agents
Pulmonary toxicity
Pyridines
Mitomycin
Cell
AKT1
Down-Regulation
Toxicology
p38 Mitogen-Activated Protein Kinases
chemistry.chemical_compound
Plasminogen Activator Inhibitor 1
medicine
Humans
Cellular Senescence
Gene knockdown
Glycogen Synthase Kinase 3 beta
Effector
Chemistry
Imidazoles
Epithelial Cells
General Medicine
respiratory system
Cell biology
Baicalein
Pulmonary Alveoli
medicine.anatomical_structure
Gene Expression Regulation
A549 Cells
Flavanones
Phosphorylation
Subjects
Details
- ISSN :
- 18793169
- Volume :
- 352
- Database :
- OpenAIRE
- Journal :
- Toxicology letters
- Accession number :
- edsair.doi.dedup.....e36aaaa0935b0854f87306b1b1296377