External factors
| Category: |
Chemical compounds |
| Experimental category: |
HL |
| Experiment: |
Flow cytometry//Western blot |
| Description: |
First, we nonspecifically elevated cellular ROS levels in proliferating IMR90 cells by hydrogen peroxide (H2O2). This procedure triggered cell cycle arrest, as judged by loss of ph-Rb and cyclin A and induction of p21, as well as CCFs and the SASP. |
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Regulatory relationship
| Regulatory pathway:
|
Mitochondria-ROS-JNK |
| Official symbol(s): |
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AIFM1-ROS1-JNK
|
| Pathway experiment: |
Western blot//Knockdown//qRT-PCR |
| Pathway description: |
JNK inhibitor treatment also diminished the SASP at the protein level in senescent cells, as shown by IL8 immunoblotting. Importantly, inhibition of JNK did not suppress mitochondrial ROS, in line with the idea that ROS act upstream of JNK activation. Knockdown of JNK1/2 strongly reduced CCF accumulation and the expression of SASP genes in senescent cells. Finally, inhibition of JNK in already senescent cells also resulted in reduction of CCFs and down-regulation of the SASP but did not rescue cell cycle arrest , corroborating our hypothesis that JNK mediates CCFs and the SASP. |
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.
Related pathway view