| External factors: | Atraric acid |
| Aging type: | Accelerate |
| Aging characteristic: |
| Category: | Chemical compounds |
| Phenotype: | Aging |
| Experiment: | SA-β-gal activity assay//SAHF//FACS analysis |
| Description: | Treatment with AA leads to the induction of SA-β-gal activity, indicating the induction of cellular senescence. These findings are further confirmed by the occurrence of SAHF . Quantitative analyses revealed that AA induces cellular senescence in LNCaP cells in a concentration-dependent manner, reaching a maximum at 30uM . Interestingly, treatment of the cells for 3 days was sufficient for the induction of cellular senescence; a longer incubation with AA did not increase the percentage of SA-β-gal-positive cells.FACS analysis revealed an increase of the number of cells in the G1 phase of the cell cycle after AA treatment. allow the regrowth of cells. |
| Regulatory pathway: | Src-Akt//Id-1-p16-pRb |
| R-EF-Pathway: | --//Activation |
| Official symbol(s): | SRC-AKT//ID1-CDKN2A-RB1 |
| Pathway experiment: | SA-β-gal activity assay//qRT-PCR |
| Pathway description: | Inhibitors of Src and Akt were used to analyze whether these factors are involved in AA-induced cellular senescence in LNCaP cells. Interestingly, cotreatment of the Src inhibitor PP2 with AA reduces the level of cellular senescence relative to single treatment with AA. Similarly, cotreatment of the Akt inhibitor with AA also reduces the level of cellular senescence, indicating that this nongenomic pathway is involved in the AA-mediated induction of cellular senescence.On the other hand a dephosphorylation of pRb was detected. Reduced phosphorylation of pRb leads to its activation and hence down-regulation of the transcription factor E2F1 (23). In line with this, a down-regulation of the pRB target E2F1 associated with the up-regulation of p16 are observed at protein level by AA treatment.An inhibitor of p16 gene expression is the cell cycle regulator Id1 via the repression of transcription factors of the E-twenty six family (26). In line with this, a reduction of Id1 gene expression after AA administration was observed . Additionally, a down-regulation of Id1 expression in LNCaP cells leads to an increase of SA -β-gal-positive cells, suggesting that Id1 inhibition is required for the activation of p16 and subsequent induction of cellular senescence triggered by AA treatment. |
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