| External factors: | Bradykinin |
| Aging type: | Prevent |
| Aging characteristic: |
| Category: | Other |
| Phenotype: | Diabetes |
| Experiment: | SA-β-gal activity assay |
| Description: | Furthermore both 0.1 nM and 1.0 nM BK dramatically inhibited H2O2-induced hEPC senescence compared to cells treated with H2O2 alone. |
| Target gene: | RB |
| R-EF-Target gene: | Downregulation |
| Official symbol(s): | RB |
| Target gene experiment: | PCR |
| Target gene description: | Notably, RB gene expression was down-regulated 176.15-fold after BK treatment. |
| Regulatory pathway: | B2R-Akt-cyclin D1-Rb//B2R-EGFR-cyclin D1-Rb |
| R-EF-Pathway: | --//-- |
| Official symbol(s): | AKT-RB1//BDKRB2-EGFR-RB1 |
| Pathway experiment: | Western blot |
| Pathway description: | P-Ser473AKT expression was down-regulated following treatment with 300 μM H2 O2 compared to control cells. Furthermore, BK increased P-Ser473AKT expression in H2 O2 -treated hEPCs, while B2R blockade and siRNA knockdown, along with PI3K antagonist treatment, reduced P-Ser473AKT expression in H2 O2 -treated hEPCs compared to treatment with BK and H2 O2 alone. However, the addition of AG1478 had no impact on P-Ser473AKT expression compared with BK treatment alone. Furthermore, there were no differences found in total AKT expression between groups, indicating that these results were due to changes in protein phosphorylation and not expression. Cyclin D1 expression was elevated in controls but reduced dramatically following H2O2 -induced senescence. Also, while BK treatment up-regulated cyclin D1 expression, treatment with either a B2R antagonist or siRNA along with PI3K antagonist treatment reduced cyclin D1 and P-Ser473AKT expression compared with BK and H2 O2 treatment alone. Treatment with AG1478 also reduced cyclin D1 expression. Additionally, we found that changes in the expression of P-Ser249 and Thr252RB paralleled those of cyclin D1. |
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