External factors
| External factors: |
Low doses of ionizing radiation |
| 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. |
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Regulatory relationship
| 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 |
| Official symbol(s): |
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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. |
Aging network
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Annotation:
The green line represents Upregulation.
The purple line represents Downregulation.
The orange line represents Activation.
The yellow line represents Inhibition.
The gray line represents Unclear.