Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for Krüppel-like factor 4.

摘要: Kruppel-like factor 4 (KLF4) is a zinc-finger-containing transcription with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which result formation. One protective response increased ROS the induction cellular senescence. Recently, we found mouse embryonic fibroblasts (MEFs) null for Klf4 are genetically unstable, as evidenced by presence DSBs. However, it yet unknown whether KLF4 involved regulating oxidative stress-induced damage. Therefore, sought determine mechanisms induce instability Klf4-deficient MEFs. With SA-β-Gal staining, show Klf4−/− MEFs enter senescence earlier than Klf4+/+ MEFs, and western blot shows accumulation p21 p53 increasing passages. In addition, immunostaining against γ-H2AX indicates level damage positively correlates accumulation. Consistent source DSB treatment NAC, reduces Our RT-PCR demonstrates have decreased expression antioxidant gene, Gsta4. The downregulation Gsta4 significant accumulation, shown DCFDA FACS analysis, thus premature Together these findings suggest mechanism protects stress at least part through regulation likely related genes. © 2014 Wiley Periodicals, Inc.