| Gene name: | PPARD |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | Human primary keratinocyte |
| Experiment: | SA-β-gal activity assay//Immunocytochemistry//Western blot |
| Description: | This increase, however, was significantly suppressed in the presence of GW501516, suggesting the involvement of PPARδ in the inhibition of UVB-induced premature senescence .A marked increase in the levels of p53 and p21 was observed in keratinocytes exposed to UVB, whereas pre-treatment with either GW501516 or NAC diminished the effect of UVB on these proteins.The level of PPARδ in keratinocytes was markedly reduced upon transfection with PPARδ siRNA in the presence of GW501516 and/or UVB radiation, whereas control siRNA, consisting of a pool of non-specific sequences, had no effect on PPARδ levels. As expected, the siRNA-mediated down-regulation of PPARδ significantly suppressed the GW501516-mediated inhibition of premature senescence and γ-H2A.X foci of keratinocytes induced by UVB radiation. |
| Target gene: | PTEN |
| Official symbol(s): | PTEN |
| R-AG-Target gene: | Upregulation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//Fluorescence microscopy |
| Target gene description: | Treatment with GW501516 markedly increased the levels of both PTEN transcript and protein in a time-dependent manner. The high levels of PTEN mRNA and protein observed 24 h after treatment with GW501516 are consistent with the observation that pre-treatment with GW501516 for 24 h, but not for 30 min, significantly suppressed the UVB-induced phosphorylation of Akt. The up-regulation of PTEN by GW501516 was suppressed in the presence of siRNA against PPARδ, suggesting that PPARδ has a causal role in the up-regulation of PTEN.Although UVB radiation significantly increased ROS generation, pre-treatment with GW501516 for 24 h significantly suppressed the effect of UVB radiation . The reduction in ROS generation in response to GW501516 was recovered in cells transfected with PPARδ siRNA, suggesting a PPARδ-dependent effect of GW501516 on ROS production. |
| Regulatory pathway: | PI3K-AKT-RAC1 |
| R-AG-Pathway: | Downregulation |
| Official symbol(s): | PIK3CA-AKT1-RAC1 |
| Pathway experiment: | Western blot//SA-β-gal activity assay//IP |
| Pathway description: | UVB-induced ROS production was significantly reduced in the presence of LY294002, a PI3K (phosphatidylinositol 3-kinase) inhibitor, but not in the presence of GF109203X, a PKC (protein kinase C) inhibitor. The effect of LY294002 was further augmented in cells incubated with GW501516. Prior incubation with DPI, a non-specific inhibitor of NADPH oxidase, significantly attenuated UVB-induced ROS production in keratinocytes. In addition, LY294002 reduced the percentage of SA β-gal-positive cells following UVB irradiation to the same extent as did GW501516. Markedly reduced in the presence of GW501516 and almost completely abolished in the presence of both GW501516 and LY294002 . Down-regulation of PPARδ by siRNA reversed the GW501516-induced decrease in Akt phosphorylation in cells exposed to UVB.Although UVB irradiation caused the rapid translocation of Rac1 to the cell membrane, the addition of GW501516 and/or LY294002 almost completely abolished the UVB-mediated translocation of Rac1. Consistent with these results, immunoblot analysis using Rac1-specific antibody revealed that Rac1 accumulated in the membrane fraction following UVB irradiation and inhibition of UVB-induced membrane translocation by both GW501516 and LY294002.UVB irradiation activated Rac1, whereas treatment with either GW501516 or LY294002 suppressed UVB-induced activation of Rac1. |
Annotation:
Loading,please wait...