| External factors: | Low doses of ionizing radiation |
| Aging type: | Prevent |
| Aging characteristic: |
| Category: | Other |
| Phenotype: | Aging |
| Experiment: | SA-β-gal activity assay//Cell morphological analysis |
| Description: | In comparison to cells treated with doxorubicin only, SA-β-Gal-positive cells decreased when cells were treated with both ionizing radiation and doxorubicin. Consistent with the appearance of SA-β-Gal activity,the morphological characteristics of senescent cells (such cells are typically large and flattened) decreased in cells treated with doxorubicin after low-dose ionizing radiation. |
| Target gene: | ERK//MAPK |
| R-EF-Target gene: | Activation |
| Official symbol(s): | ERK//MAPK |
| Target gene experiment: | Western blot//SA-β-gal activity assay |
| Target gene description: | ERK/MAPK was weakly induced by low-dose radiation alone, but was significantly increased in cells treated with a combination of a low dose of radiation and doxorubicin. SA-?-Gal activity also significantly increased in cells treated with PD980590. The SA-?-Gal activity of cells treated with low doses of ionizing radiation was restored to control levels by treatment with PD98059. Thus, low doses of ionizing radiation inhibited doxorubicin-induced senescence through induction of ERK/MAPK activity. |
| Regulatory pathway: | p38-p53 |
| R-EF-Pathway: | -- |
| Official symbol(s): | MAPK14-TP53 |
| Pathway experiment: | Western blot//SA-β-gal activity assay |
| Pathway description: | The phosphorylation of p38 kinase significantly increased at 4 days after doxorubicin treatment was suppressed by low doses of ionizing radiation without changing protein levels of p38 kinase.Consistently, SA-?-Gal activity was decreased in cells treated with doxorubicin following a chemical inhibitor of p38 kinase, SB203580.The phosphorylation of p53 in MCF7 cells treated with a combination of doxorubicin and a chemical inhibitor of p38 kinase, SB203580, was significantly decreased from control levels, implying that p38 kinase-dependent phosphorylation of p53 is essential for doxorubicin-induced senescence. |
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