| Gene name: | CLU |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | IMR-90 |
| Experiment: | SA-β-gal activity assay//Knockdown |
| Description: | Enhanced senescence was confirmed by significant differences in the SA-β-gal+ cells, where at least two-fold increases were noted compared to untreated pTRIPZ-shCLU IMR-90 cells that expressed sCLU at day 39. Dox-inducible non-silencing shRNA had no affect on sCLU expression, both population doubling times and %SA-β-gal+ cells were not significantly different with or without Dox exposure over the life of the IMR-90 cultures. |
| Target gene: | ATM |
| Official symbol(s): | ATM |
| R-AG-Target gene: | -- |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot |
| Target gene description: | AT2052 cells expressed significantly lower basal level expression of sCLU compared to wild-type ATM+ IMR-90 cells. |
| Regulatory pathway: | IGF-1R-MAPK-ERK1/2-EGR-1 |
| R-AG-Pathway: | -- |
| Official symbol(s): | IGF1R-MAPK-EGR1 |
| Pathway experiment: | ELISA//Western blot//TUNEL assay |
| Pathway description: | Indeed, IGF-1 expression was approximately two-fold higher in conditioned media from senescent compared to young IMR-90 cells. Analyses of differential signal transduction responses in senescent versus young IMR-90 cells showed that IGF-1 receptor (IGF-1R) levels were activated (elevated P-IGF-1R/tIGF-1R) in senescent cells; antibodies to human IGF-1R are not ideal. Src and Erk-1/2 kinase levels were also elevated in middleaged and senescent compared to young IMR-90 cells. The transcription factor, Egr-1, which binds the hCLU promoter and mediates sCLU expression, was significantly increased during senescence in IMR-90 cells. To further confirm the specificity of IGF-1/IGF-1R/MAPK/ERK-1/2/Egr-1 signaling in sCLU induction during senescence, we treated senescent IMR90 cells with the IGF-1R inhibitor, AG1024, which effectively blocked IR-induced sCLU expression and also suppressed sCLU expression in senescent IMR-90 cells in a dose-dependent manner . |
Annotation:
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