External factors
| External factors: |
Rapamycin |
| Category: |
Chemical compounds |
| Description: |
Rapamycin significantly decreased IL6 secretion by 3 strains of normal human fibroblasts, and 2 strains of immortal, but non-tumorigenic human breast epithelial cell lines (MCF-10A and 184A1)— all induced to senesce by ionizing radiation (10 Gy X-irradiation).Rapamycin also suppressed IL6 secretion by human fibroblasts induced to senesce by other stimuli. |
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Regulatory relationship
| R-EF-Target gene:
|
Downregulation |
| Target gene experiment: |
qPCR |
| Target gene description: |
Rapamycin significantly decreased the translational efficiency of IL1A mRNA, and to a lesser extent IL1B, IL6 and IL8 mRNAs,in senescent cells. |
| Regulatory pathway:
|
mTOR//NF-κB |
| R-EF-Pathway:
|
--//Downregulation |
| Official symbol(s): |
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MTOR//NFKB1
|
| Pathway experiment: |
Knockdown//ELISA//Luciferase reporter assay |
| Pathway description: |
ShRNA against raptor, but not GFP, severely blunted IL6 secretion by senescent cells. Likewise, shRNA-mediated depletion of MTOR reduced senescence-associated IL6 secretion by >90% .We infected HCA2 cells with a lentivirus carrying an NF-κB–luciferase reporter, and measured the effect of rapamycin on reporter activity. Rapamycin reduced NF-κB activity by 80%. |
Aging network
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.