Acute Activation of AMP-Activated Protein Kinase Prevents H2O2-Induced Premature Senescence in Primary Human Keratinocytes

摘要: We investigated the effects of AMPK on H2O2-induced premature senescence in primary human keratinocytes. Incubation with 50 µM H2O2 for 2 h resulted characteristic increases senescence-associated s-galactosidase (SA-gal) staining 3 days later and no changes or p38 MAPK activity. The increase SA-gal was preceded by both p53 phosphorylation (S15) (1 h) transactivation (6 abundance cyclin inhibitor p21CIP1 (16 h). AICAR resveratrol, which activated AMPK, prevented SA-Gal p21 abundance. In addition, diminished transactivation. decreases expression induced resveratrol were pharmacological Compound C, a DN-AMPK knock-down shRNA. Likewise, knockdown sufficient to induce senescence, even absence exogenous H2O2. As reported others, we found that activation itself increased at S15 embryonic fibroblasts (MEF), whereas under same conditions it decreased keratinocytes, aortic endothelial cells, HT1080 fibrosarcoma cells. conclusion, results indicate low concentrations causes keratinocytes activating p53-p21CIP1 signaling these can be acute enhanced downregulation. They also suggest this action may cell context-specific.